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Protocolized Diuretic Strategy in Cardiorenal Failure (ProDiuS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01921829
Recruitment Status : Terminated (Due to futility due to lower than expected recruitment)
First Posted : August 13, 2013
Results First Posted : July 17, 2017
Last Update Posted : August 21, 2017
Sponsor:
Information provided by (Responsible Party):
Kelly V. Liang, MD, University of Pittsburgh

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Conditions Cardiac Failure
Renal Failure
Kidney Failure
Intervention Drug: Protocolized Diuretic Strategy
Enrollment 19
Recruitment Details Patients were recruited from the UPMC Heart Failure and Cardiology services, from July 2015-Nov 2016.
Pre-assignment Details One participant was enrolled but withdrew consent before receiving any randomized treatment protocol. Therefore, that patient was withdrawn.
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist. Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Period Title: Overall Study
Started 10 9
Completed 10 8
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Arm/Group Title Usual Care Protocolized Diuretic Strategy Total
Hide Arm/Group Description Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist. Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced. Total of all reporting groups
Overall Number of Baseline Participants 10 8 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 8 participants 18 participants
68.9  (8.6) 68.4  (6.9) 68.7  (7.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
Female
3
  30.0%
2
  25.0%
5
  27.8%
Male
7
  70.0%
6
  75.0%
13
  72.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  10.0%
0
   0.0%
1
   5.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  30.0%
0
   0.0%
3
  16.7%
White
6
  60.0%
8
 100.0%
14
  77.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Years of education  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 8 participants 18 participants
13.5  (2.3) 12.9  (2.4) 13.2  (2.3)
Smoking  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
Current
0
   0.0%
0
   0.0%
0
   0.0%
Past
5
  50.0%
6
  75.0%
11
  61.1%
Never
5
  50.0%
2
  25.0%
7
  38.9%
Alcohol use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
1
  10.0%
2
  25.0%
3
  16.7%
Caffeine use   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
8
  88.9%
6
  75.0%
14
  82.4%
[1]
Measure Analysis Population Description: Missing data
Cardiomyopathy type  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
Ischemic
5
  50.0%
5
  62.5%
10
  55.6%
Dilated
1
  10.0%
2
  25.0%
3
  16.7%
Hypertensive
0
   0.0%
1
  12.5%
1
   5.6%
Other
4
  40.0%
0
   0.0%
4
  22.2%
NYHA Class   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 6 participants 15 participants
II
2
  22.2%
2
  33.3%
4
  26.7%
III
5
  55.6%
4
  66.7%
9
  60.0%
IV
2
  22.2%
0
   0.0%
2
  13.3%
[1]
Measure Description:

New York Heart Association (NYHA) Functional Classes:

I - No limitation of physical activity. Ordinary physical activity does not cause heart failure (HF) symptoms like undue fatigue, palpitation, dyspnea (shortness of breath).

II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in HF symptoms.

III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity results in HF symptoms.

IV - Unable to carry on any physical activity without discomfort. HF symptoms occur at rest and increase with any physical activity.

[2]
Measure Analysis Population Description: Missing data
Left ventricular ejection fraction   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 15 participants
20-25%
3
  37.5%
2
  28.6%
5
  33.3%
25-30%
0
   0.0%
2
  28.6%
2
  13.3%
30-35%
1
  12.5%
0
   0.0%
1
   6.7%
Unknown
4
  50.0%
3
  42.9%
7
  46.7%
[1]
Measure Analysis Population Description: Missing data
Right ventricular function   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 14 participants
Normal
3
  37.5%
5
  83.3%
8
  57.1%
Reduced
5
  62.5%
1
  16.7%
6
  42.9%
[1]
Measure Analysis Population Description: Missing data
Mitral regurgitation   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 13 participants
4
  57.1%
3
  50.0%
7
  53.8%
[1]
Measure Analysis Population Description: Missing data
Tricuspid regurgitation   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 14 participants
6
  75.0%
4
  66.7%
10
  71.4%
[1]
Measure Analysis Population Description: Missing data
Jugular venous pressure elevated   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
6
  66.7%
7
  87.5%
13
  76.5%
[1]
Measure Analysis Population Description: Missing data
Edema grade   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 7 participants 16 participants
2+
7
  77.8%
2
  28.6%
9
  56.3%
3+
1
  11.1%
3
  42.9%
4
  25.0%
Unknown
1
  11.1%
2
  28.6%
3
  18.8%
[1]
Measure Description:

Edema grades based on palpation of skin:

  1. - There is a barely detectable 2mm depression. Not easily seen but can be felt. Immediate rebound.
  2. - There is a 4mm deep pit. A few seconds to rebound.
  3. - There is a 6mm deep pit. 10-12 seconds to rebound.
  4. - There is an 8mm deep pit (very deep). >20 seconds to rebound.
[2]
Measure Analysis Population Description: Missing data
Hypertension  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
9
  90.0%
7
  87.5%
16
  88.9%
Diabetes mellitus   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
5
  55.6%
5
  62.5%
10
  58.8%
[1]
Measure Analysis Population Description: Missing data
Chronic obstructive pulmonary disease   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
2
  22.2%
3
  37.5%
5
  29.4%
[1]
Measure Analysis Population Description: Missing data
Coronary artery disease   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
5
  55.6%
6
  75.0%
11
  64.7%
[1]
Measure Analysis Population Description: Missing data
Depression   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
2
  22.2%
2
  25.0%
4
  23.5%
[1]
Measure Analysis Population Description: Missing data
Stroke   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
4
  44.4%
0
   0.0%
4
  23.5%
[1]
Measure Analysis Population Description: Missing data
Peripheral vascular disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
4
  40.0%
0
   0.0%
4
  22.2%
Hyperlipidemia   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
5
  55.6%
5
  62.5%
10
  58.8%
[1]
Measure Analysis Population Description: Missing data
Atrial fibrillation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
5
  50.0%
6
  75.0%
11
  61.1%
Coronary artery bypass surgery   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
3
  33.3%
3
  37.5%
6
  35.3%
[1]
Measure Analysis Population Description: Missing data
Implantable cardioverter defibrillator  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 8 participants 18 participants
5
  50.0%
2
  25.0%
7
  38.9%
Cardiac resynchronization therapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 17 participants
1
  11.1%
1
  12.5%
2
  11.8%
[1]
Measure Analysis Population Description: Missing data
Diuretic dose   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/day
Number Analyzed 10 participants 8 participants 18 participants
242.5  (112.7) 166.3  (55.5) 214.2  (99.7)
[1]
Measure Description: (furosemide equivalent)
Creatinine  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 10 participants 8 participants 18 participants
1.9  (0.5) 2.2  (0.8) 2.0  (0.6)
Blood urea nitrogen  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 10 participants 8 participants 18 participants
38.2  (12.5) 56.3  (38.8) 45.6  (27.1)
Brain natriuretic peptide  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 10 participants 8 participants 18 participants
855.3  (690.7) 530.4  (363.7) 710.9  (578.5)
1.Primary Outcome
Title Change in Body Weight (kg) From Randomization to Day 4 or Date of Discharge (Whichever Comes First)
Hide Description The change in body weight (kg) from randomization to day 4 or date of discharge will be determined by the difference between body weight at day 4 after randomization or date of discharge (whichever comes first) and body weight taken at baseline measured in the hospital on standard scales without shoes and wearing a hospital gown, measured before breakfast and post-voiding.
Time Frame 4 days (96 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
One patient from ProDiuS arm withdrew before undergoing any randomized treatment.
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: kg
-2.07  (4.84) -6.12  (1.95)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Length of Hospitalization
Hide Description Length of hospitalization will be ascertained from admission date to date of discharge.
Time Frame 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
One participant from the ProDiuS arm withdrew consent before undergoing any randomized treatment.
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: days
7.5  (12.0) 8.0  (6.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Number of Rehospitalizations for Heart Failure (HF)
Hide Description Number of rehospitalizations for HF will be ascertained based on chart review of admissions with HF as a coded diagnosis, evidence of clinical volume overload, and treatment with intravenous diuretics.
Time Frame Up to 3 months (assessed at 1 month and 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Measure Type: Number
Unit of Measure: hospitalizations
3 1
4.Secondary Outcome
Title Number of Total Rehospitalizations
Hide Description Number of rehospitalizations will be ascertained based on chart review of admissions to any hospital after the index hospitalization
Time Frame Up to 3 months (assessed at 1 month and 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: hospitalizations
0.0  (1.0) 0.5  (5.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title All-cause Mortality
Hide Description All-cause mortality will be ascertained based on chart review of vital status (alive/dead) and cause of death.
Time Frame Up to 3 months (assessed at 1 month and 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 9
Measure Type: Count of Participants
Unit of Measure: Participants
1
  10.0%
4
  44.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Difference From Baseline to 1 Month in Change in Right Internal Jugular Vein (RIJV) Cross-sectional Area (CSA) Pre- and Post-Valsalva
Hide Description The change in cross-sectional area (CSA) of the right internal jugular vein (RIJV) pre- and post-Valsalva is a measurement of venous compliance and was determined noninvasively with Doppler ultrasound. An increase in RIJV CSA >17% during Valsalva effectively rules out elevated right atrial pressure (RAP) and suggests effective volume removal or decongestion. The difference between baseline and 1 month values of change in RIJV CSA are reported.
Time Frame Up to 1 month (measured at baseline and 1 mo)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: cm^2
0.11  (1.03) 0.22  (0.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Fluid Balance
Hide Description Strict intake (oral intake, intravenous medications, fluids, etc.) and output (urine, emesis, stools, drains, etc.) will be documented by the nurses on the HF floors per routine clinical protocol for all patients. Fluid balance will be determined by subtracting the volume of total intake from the volume of total output (in mL) over 24 hours (7 am to 7 am or the preceding 24-h period if no 7 am to 7 am period is available). Fluid balance and urine output will be ascertained by chart review daily during the intervention while the participants are hospitalized.
Time Frame Daily while in hospital
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: mL/day
-1077  (345) -590  (1268)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Acute Kidney Injury
Hide Description Acute kidney injury will be defined based a rise in Cr ≥0.3 mg/dL.
Time Frame Daily while in hospital, 1 mo & 3 mos
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Measure Type: Count of Participants
Unit of Measure: Participants
5
  50.0%
4
  50.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Secondary Outcome
Title Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score Change at 1 Month
Hide Description The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Time Frame Baseline to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.64  (18.01) 19.89  (9.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score Change at 1 Month
Hide Description The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Time Frame Baseline to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
15.65  (14.41) 16.20  (13.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
11.Secondary Outcome
Title SF-36 Mental Component Score (MCS) Change at 1 Month
Hide Description The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame Baseline to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.84  (15.41) 4.96  (1.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
12.Secondary Outcome
Title SF-36 Physical Component Score (PCS) Change at 1 Month
Hide Description The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame Baseline to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
12.31  (11.72) 11.95  (11.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
13.Secondary Outcome
Title PHQ-9 Depression Index Change at 1 Month
Hide Description

The Patient Health Questionnaire (PHQ-9) Depression Index is a well-established index of depression and has been validated in many patient populations. Its scores range from 0-27 with increasing scores representing increasing depression severity. Score categories represent depression severity and management recommendations:

0-4 - Minimal or no depression. Monitor; may not require treatment. 5-9 - Mild. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.

10-14 - Moderate. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.

15-19 - Moderately severe. Warrants active treatment with psychotherapy, medications, or combination.

20-27 - Severe. Warrants active treatment with psychotherapy, medications, or combination.

Time Frame Baseline to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
-3.5  (6.0) -7.0  (10.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
14.Secondary Outcome
Title PSQI Total Score Change at 1 Month
Hide Description The Pittsburgh Sleep Quality Index (PSQI) is the most widely used global sleep assessment and has been studied in the renal transplant population. Consisting of 19 items, the PSQI measures several different aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency (i.e., how long it takes to fall asleep), sleep duration, habitual sleep efficiency (i.e., the percentage of time in bed that one is asleep), sleep disturbances, use of sleeping medication, and daytime dysfunction. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.
Time Frame Baseline to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.5  (5.0) -1.0  (5.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
15.Secondary Outcome
Title Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score Change at 3 Months
Hide Description The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Time Frame Baseline to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
13.84  (17.04) 24.47  (12.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
16.Secondary Outcome
Title Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Score Change at 3 Months
Hide Description The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well-validated 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A mean difference over time of 5 points on the KCCQ Overall Summary Scale reflects a clinically significant change in heart failure status. A 10 point decline in KCCQ scores has important prognostic significance in terms of survival.
Time Frame Baseline to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
9.00  (17.24) 23.00  (22.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
17.Secondary Outcome
Title SF-36 Mental Component Score (MCS) Change at 3 Months
Hide Description The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame Baseline to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.06  (10.83) -0.40  (0.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
18.Secondary Outcome
Title SF-36 Physical Component Score (PCS) Change at 3 Months
Hide Description The Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) is a well-validated generic HRQOL questionnaire that generates two composite scores: the Physical Component Score (PCS) and Mental Component Score (MCS). The PCS aggregates items from Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, and Social Functioning. The MCS aggregates items from Role-Emotional, Mental Health, General Health, Vitality, and Social Functioning. The mean for each summary scale is 50 points with standard deviation of 10 points. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame Baseline to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
16.25  (8.50) 12.90  (10.61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
19.Secondary Outcome
Title PHQ-9 Depression Index Change at 3 Months
Hide Description

The Patient Health Questionnaire (PHQ-9) Depression Index is a well-established index of depression and has been validated in many patient populations. Its scoring ranges from 0-27 with increasing scores representing increasing depression severity. Score categories determine depression severity and recommended management:

0-4 - Minimal or none. Monitor; may not require treatment. 5-9 - Mild. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.

10-14 - Moderate. Use clinical judgment (symptom duration, functional impairment) to determine necessity of treatment.

15-19 - Moderately severe. Warrants active treatment with psychotherapy, medications, or combination.

20-27 - Severe. Warrants active treatment with psychotherapy, medications, or combination.

Time Frame Baseline to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.00  (5.00) -4.00  (7.50)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
20.Secondary Outcome
Title PSQI Total Score Change at 3 Months
Hide Description The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over a 1-month time interval. The measure consists of 19 individual items, creating 7 components that produce one global score, and takes 5-10 minutes to complete. Consisting of 19 items, the PSQI measures several different aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Traditionally, the items from the PSQI have been summed to create a total score to measure overall sleep quality.
Time Frame Baseline to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description:
Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.00  (5.00) -4.00  (8.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
21.Other Pre-specified Outcome
Title Adverse Events
Hide Description Hypokalemia (K <3.0 milliequivalents (mEq)/L), hypotension (systolic BP <90 mmHg), hyponatremia (Na <130 mEq/L), arrhythmias, cramps, and other (recorded as short description).
Time Frame Daily while in hospital , 1 mo, & 3 mos
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[Not Specified]
Arm/Group Title Usual Care Protocolized Diuretic Strategy
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Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist.
Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: events
2.0  (6.0) 3.5  (7.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Usual Care, Protocolized Diuretic Strategy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.95
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame 3 months
Adverse Event Reporting Description Acute kidney injury, hypokalemia (K <3.0 mEq/L), hypotension (systolic BP <90 mmHg), hyponatremia (Na <130 mEq/L), arrhythmias, cramps, and other were recorded. For each adverse event, diagnosis, date of onset, date of resolution, severity, whether it was unexpected, related to the intervention, serious adverse event (SAE), type of SAE, whether the blind was broken, and the outcome were recorded.
 
Arm/Group Title Usual Care Protocolized Diuretic Strategy
Hide Arm/Group Description Participants randomized to the Usual Care group (control arm) will receive escalating diuretics and medical therapy per HF guidelines published by the American College of Cardiology (ACC)/American Heart Association (AHA) and Heart Failure Society of America (HFSA), dosed in variable fashion at the discretion of the treating cardiologist. Participants randomized to the Protocolized Diuretic Strategy group will receive escalating diuretics according to an algorithm targeting a goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide). If UO is < 3 L/day, diuretic regimen will be increased. If UO is 3-5 L/day, diuretic regimen will be continued at current doses. If UO is > 5 L/day, diuretic regimen will be reduced.
All-Cause Mortality
Usual Care Protocolized Diuretic Strategy
Affected / at Risk (%) Affected / at Risk (%)
Total   1/10 (10.00%)      4/9 (44.44%)    
Hide Serious Adverse Events
Usual Care Protocolized Diuretic Strategy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/10 (20.00%)      1/9 (11.11%)    
Cardiac disorders     
Cardiac arrhythmia * 1  2/10 (20.00%)  4 1/9 (11.11%)  2
Hospitalization  1 [1]  2/10 (20.00%)  3 0/9 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Hospitalization for non-cardiac cause  1 [2]  1/10 (10.00%)  1 0/9 (0.00%)  0
1
Term from vocabulary, MedDRA (10.0)
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
[1]
Volume overload or heart transplant
[2]
Acute gout flare, leukocytosis
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Usual Care Protocolized Diuretic Strategy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/10 (70.00%)      2/9 (22.22%)    
Cardiac disorders     
Chest pain  1  1/10 (10.00%)  2 0/9 (0.00%)  0
Hypotension  1  1/10 (10.00%)  1 0/9 (0.00%)  0
General disorders     
Fall  1 [1]  0/10 (0.00%)  0 1/9 (11.11%)  1
Severe head/neck pain  1  1/10 (10.00%)  1 0/9 (0.00%)  0
Leg and abdominal cramps  1  1/10 (10.00%)  1 0/9 (0.00%)  0
Psychiatric disorders     
Depression  1 [2]  1/10 (10.00%)  1 0/9 (0.00%)  0
Renal and urinary disorders     
Hypokalemia  1  3/10 (30.00%)  4 1/9 (11.11%)  1
Hyponatremia  1  4/10 (40.00%)  5 2/9 (22.22%)  2
Hyperphosphatemia  1  2/10 (20.00%)  2 0/9 (0.00%)  0
Worsening acute kidney injury  1  6/10 (60.00%)  9 1/9 (11.11%)  2
Hypercalcemia  1  1/10 (10.00%)  1 1/9 (11.11%)  1
Hypermagnesemia  1  1/10 (10.00%)  1 1/9 (11.11%)  1
Hyperkalemia  1  1/10 (10.00%)  1 0/9 (0.00%)  0
1
Term from vocabulary, MedDRA (10.0)
Indicates events were collected by systematic assessment
[1]
Hitting head on wall
[2]
High depression score requiring follow up from psychiatry
Early termination leading to small numbers of subjects analyzed
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Dr. Kelly Liang
Organization: University of Pittsburgh
Phone: 507-269-7812
EMail: liangk@upmc.edu
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Responsible Party: Kelly V. Liang, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01921829    
Other Study ID Numbers: PRO13040071
First Submitted: July 23, 2013
First Posted: August 13, 2013
Results First Submitted: April 12, 2017
Results First Posted: July 17, 2017
Last Update Posted: August 21, 2017