Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 58 of 116 for:    Atenolol

Hypertension in Hemodialysis Patients (Aim 3)

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: NCT00582114
Recruitment Status : Terminated (Stopped by data safety monitoring board)
First Posted : December 28, 2007
Results First Posted : January 18, 2016
Last Update Posted : January 18, 2016
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Indiana University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hemodialysis
Hypertension
Left Ventricular Hypertrophy
Interventions Drug: Lisinopril
Drug: Atenolol
Enrollment 200
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Atenolol Lisinopril
Hide Arm/Group Description Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other angiotensin converting enzyme (ACE) inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg. Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.
Period Title: Overall Study
Started 100 100
Completed 58 46
Not Completed 42 54
Reason Not Completed
Death             4             4
Kidney Transplant             3             1
Lost to Follow-up             7             6
Withdrawal by Subject             8             16
Adverse Event             1             1
Physician Decision             0             6
Stopped by data safety monitoring board             19             20
Arm/Group Title Atenolol Lisinopril Total
Hide Arm/Group Description Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg. Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg. Total of all reporting groups
Overall Number of Baseline Participants 100 100 200
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 100 participants 200 participants
52.5  (11.7) 53.1  (13.5) 52.7  (12.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Female
27
  27.0%
42
  42.0%
69
  34.5%
Male
73
  73.0%
58
  58.0%
131
  65.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Hispanic or Latino
1
   1.0%
0
   0.0%
1
   0.5%
Not Hispanic or Latino
99
  99.0%
100
 100.0%
199
  99.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Blacks 86 86 172
Non-blacks 14 14 28
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 100 participants 100 participants 200 participants
100 100 200
Etiology of chronic kidney disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Diabetes mellitus 29 27 56
Hypertension 54 46 100
Glomerulonephritis 4 5 9
Polycystic kidney disease 0 1 1
Other etiologies 13 21 34
Dialysis vintage  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 100 participants 200 participants
4.2  (4.4) 3.9  (4.2) 4.1  (4.3)
Anuric  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
68 66 134
Education  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 100 participants 200 participants
12  (2) 12  (2) 12  (2)
Comorbid conditions  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Diabetes mellitus 43 43 86
Hospitalized heart failure 25 37 62
Coronary artery disease 22 31 53
Coronary revascularization 4 15 19
Cerebrovascular disease 13 20 33
Peripheral vascular disease 10 11 21
Marital status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Single 53 56 109
Married 23 19 42
Divorced/separated 18 15 33
Widowed 6 10 16
Employed  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Working 11 7 18
Not working 67 70 137
Retired 22 23 45
Income  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
< $25,000 84 80 164
>= $25,000 10 7 17
Refused 6 13 19
Smoking  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Current smoker 43 43 86
Non-smoker 57 57 114
Alcohol  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Drinks alcohol 27 19 46
Does not drink alcohol 73 81 154
Height  
Mean (Standard Deviation)
Unit of measure:  Inches
Number Analyzed 100 participants 100 participants 200 participants
68.3  (4.1) 67.6  (3.7) 67.9  (3.9)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 100 participants 100 participants 200 participants
85.1  (21.7) 80.9  (24.3) 83  (23.1)
Body mass index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 100 participants 100 participants 200 participants
28.4  (7) 27.5  (8.3) 27.9  (7.7)
Access type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants 100 participants 200 participants
Fistula 59 59 118
Graft 16 14 30
Catheter 25 27 52
Blood flow rate  
Mean (Standard Deviation)
Unit of measure:  mL/min
Number Analyzed 100 participants 100 participants 200 participants
394.3  (30.9) 392.4  (36.4) 393.4  (33.7)
Dialysate flow rate  
Mean (Standard Deviation)
Unit of measure:  mL/min
Number Analyzed 100 participants 100 participants 200 participants
779.6  (61.9) 761.3  (82) 770.4  (73)
Dialysis duration  
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 100 participants 100 participants 200 participants
Prescribed dialysis duration 239.4  (19) 239.4  (25.9) 239.4  (22.7)
Delivered dialysis duration 224.1  (34.7) 219.8  (33.7) 222  (34.2)
Urea reduction ratio  
Mean (Standard Deviation)
Unit of measure:  %
Number Analyzed 100 participants 100 participants 200 participants
74  (8) 76  (8) 75  (8)
Albumin  
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 100 participants 100 participants 200 participants
3.6  (0.5) 3.6  (0.5) 3.6  (0.5)
Hemoglobin  
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 100 participants 100 participants 200 participants
11.3  (1.2) 11.3  (1.4) 11.3  (1.3)
Creatinine  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 100 participants 100 participants 200 participants
10.3  (3.5) 10  (3.6) 10.1  (3.6)
1.Primary Outcome
Title The Primary End Point is the Regression of Left Ventricular Hypertrophy (LVH) by Echocardiographic Criteria From Baseline to 1 Year.
Hide Description The primary outcome of the study was the average reduction in left ventricular mass indexed for body surface area from baseline to 1 year. A mixed model was used with left ventricular mass index (LVMI) as the outcome variable. Fixed effects were indicator variables for time, treatment and their interaction. Random effect was subject and statistical inference was made using the maximum likelihood estimator. No imputation was made for missing data.
Time Frame Baseline, 6 months, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary outcome of the study was the average reduction in left ventricular mass indexed for body surface area from baseline to 1 year. The analysis was performed by intention to treat, if the patient received at least one dose of the randomized drug regardless of the availability of a post-baseline echocardiogram.
Arm/Group Title Atenolol Lisinopril
Hide Arm/Group Description:
Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.
Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.
Overall Number of Participants Analyzed 100 100
Mean (Standard Deviation)
Unit of Measure: g/m^2
LVMI Change from baseline, 6 months -8.4  (5.1) -3.4  (5.5)
LVMI Change from baseline, 12 months -21.5  (5.7) -15.1  (6.2)
2.Other Pre-specified Outcome
Title Serious Adverse Events and Cardiovascular Events That Led to Trial Termination
Hide Description Cardiovascular events were counted by subject and included the following: myocardial infarction (MI), stroke, hospitalization for congestive heart failure (CHF), hospitalized angina, arrhythmias, cardiac arrest, coronary revascularization and heart valve replacement. Adverse events reported are those during the course of 12 months of participation in the trial. All serious adverse events were adjudicated by R.A. and A.D.S. who were masked to the drug assignment at the time of adjudication. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. The cardiovascular event rate was calculated by treatment group assignment. Incidence rate ratio (IRR) by treatment was then determined along with the 95% confidence intervals (95% CIs). As a post hoc analysis, we also determined the narrower definition of cardiovascular events per group that included MI, stroke, CHF, or cardiovascular death.
Time Frame 1 yr
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atenolol Lisinopril
Hide Arm/Group Description:
Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.
Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.
Overall Number of Participants Analyzed 100 100
Measure Type: Number
Unit of Measure: events/100 patient-years
Incidence rate, cardiovasular events 24.6 58
Incidence rate, combined MI, stroke, CHF, CV death 13.5 31
Incidence rate, congest heart failure 6.2 20.2
Incidence rate, all-cause hospitalizations 89.9 144.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atenolol, Lisinopril
Comments Cardiovascular events were counted by subject and included the following: myocardial infarction, stroke, hospitalization for congestive heart failure, hospitalized angina, arrhythmias, cardiac arrest, coronary revascularization and heart valve replacement. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals (95% CIs).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.36
Confidence Interval (2-Sided) 95%
1.36 to 4.23
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atenolol, Lisinopril
Comments As a post hoc analysis, we determined the narrower definition of cardiovascular events per group that included myocardial infarction, stroke, congestive heart failure or cardiovascular death. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals (95% CIs).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.29
Confidence Interval (2-Sided) 95%
1.07 to 5.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atenolol, Lisinopril
Comments Hospitalization for congestive heart failure between groups was analyzed. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.13
Confidence Interval (2-Sided) 95%
1.08 to 10.99
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Atenolol, Lisinopril
Comments All-cause hospitalizations between groups were analyzed. The duration of participation in the study per subject, which according to the trial design could be up to 12 months, was determined. Incidence rate ratio (IRR) by treatment was then determined along with the 95%confidence intervals.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
1.18 to 2.19
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Atenolol Lisinopril
Hide Arm/Group Description Atenolol: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg. Lisinopril: Patients will be randomized into two groups, one that is beta blocker based, the other ACE inhibitor (lisinopril) based. Patients who are on no medications will receive atenolol 25 mg. t.i.w. or lisinopril 10 mg. t.i.w. for one month at the end of which, dose will be titrated to twice the drug doses following monthly interval to another doubling of dose. If BP is still poorly controlled felodipine will be added. Other antihypertensive therapies will be added to control home BP to <140/90 mm Hg.
All-Cause Mortality
Atenolol Lisinopril
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Atenolol Lisinopril
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   58/100 (58.00%)      70/100 (70.00%)    
Cardiac disorders     
Angina   0/100 (0.00%)  0 2/100 (2.00%)  2
Arrhythmia   2/100 (2.00%)  2 3/100 (3.00%)  5
Cardiac arrest   0/100 (0.00%)  0 2/100 (2.00%)  2
Congestive heart failure   5/100 (5.00%)  5 10/100 (10.00%)  15
Myocardial infarction   2/100 (2.00%)  2 3/100 (3.00%)  3
Peripheral vascular disease   1/100 (1.00%)  1 5/100 (5.00%)  6
Revascularization   3/100 (3.00%)  4 4/100 (4.00%)  4
Stroke   2/100 (2.00%)  2 2/100 (2.00%)  2
Valve replacement surgery   1/100 (1.00%)  1 1/100 (1.00%)  1
Cardiovascular death   2/100 (2.00%)  2 3/100 (3.00%)  3
Endocrine disorders     
Parathyroidectomy   3/100 (3.00%)  3 1/100 (1.00%)  1
Hyperglycemia   1/100 (1.00%)  2 3/100 (3.00%)  3
Hypoglycemia   2/100 (2.00%)  3 4/100 (4.00%)  4
Gastrointestinal disorders     
Bowel-related   3/100 (3.00%)  3 5/100 (5.00%)  5
Gastrointestinal bleed   2/100 (2.00%)  4 5/100 (5.00%)  7
General disorders     
Noncardiovascular death   2/100 (2.00%)  2 1/100 (1.00%)  1
Falls   6/100 (6.00%)  6 3/100 (3.00%)  3
Hypertensive crisis   3/100 (3.00%)  3 10/100 (10.00%)  11
Hypotension with hospitalization   6/100 (6.00%)  8 5/100 (5.00%)  5
Miscellaneous   12/100 (12.00%)  14 18/100 (18.00%)  24
Hepatobiliary disorders     
Biliary-related   1/100 (1.00%)  1 2/100 (2.00%)  2
Infections and infestations     
Infections   24/100 (24.00%)  30 20/100 (20.00%)  29
Musculoskeletal and connective tissue disorders     
Fractures   7/100 (7.00%)  7 1/100 (1.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer-related complications   2/100 (2.00%)  4 2/100 (2.00%)  3
Nervous system disorders     
Central nervous system   3/100 (3.00%)  3 3/100 (3.00%)  5
Renal and urinary disorders     
Access-related   17/100 (17.00%)  24 19/100 (19.00%)  30
Hyperkalemia   3/100 (3.00%)  3 10/100 (10.00%)  10
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Atenolol Lisinopril
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/100 (44.00%)      29/100 (29.00%)    
Gastrointestinal disorders     
Gastrointestinal disorders   5/100 (5.00%)  6 6/100 (6.00%)  6
General disorders     
Fatigue   20/100 (20.00%)  25 6/100 (6.00%)  12
bradycardia   2/100 (2.00%)  3 1/100 (1.00%)  1
Intradialytic hypotension   6/100 (6.00%)  7 4/100 (4.00%)  4
tachycardia   1/100 (1.00%)  1 1/100 (1.00%)  1
Dialysis access-related events   0/100 (0.00%)  0 1/100 (1.00%)  1
Hypertension   1/100 (1.00%)  1 2/100 (2.00%)  3
Other   19/100 (19.00%)  23 17/100 (17.00%)  29
Infections and infestations     
Upper respiratory infection   1/100 (1.00%)  1 2/100 (2.00%)  4
Skin and subcutaneous tissue disorders     
Rash   1/100 (1.00%)  2 2/100 (2.00%)  2
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Dr. Rajiv Agarwal
Organization: Professor of Medicine
Phone: 317-988-2241
EMail: ragarwal@iu.edu
Layout table for additonal information
Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00582114     History of Changes
Other Study ID Numbers: 0306-13
R01DK062030 ( U.S. NIH Grant/Contract )
NIH-NIDDK-5RO1-062030
First Submitted: December 20, 2007
First Posted: December 28, 2007
Results First Submitted: October 5, 2015
Results First Posted: January 18, 2016
Last Update Posted: January 18, 2016