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Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure (IRONOUT)

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: NCT02188784
Recruitment Status : Completed
First Posted : July 14, 2014
Results First Posted : May 15, 2017
Last Update Posted : July 11, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Adrian Hernandez, Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Heart Failure
Interventions Drug: Polysaccharide Iron Complex 150 mg
Drug: Placebo (for Polysaccharide Iron Complex)
Enrollment 225
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Period Title: Overall Study
Started 111 114
Completed 102 [1] 101 [1]
Not Completed 9 13
Reason Not Completed
Death             3             1
Lost to Follow-up             1             0
Withdrawal by Subject             3             9
Physician Decision             2             3
[1]
Patients completing the protocol excluding death, lost to follow-up and withdrawn consent.
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg) Total
Hide Arm/Group Description

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Total of all reporting groups
Overall Number of Baseline Participants 111 114 225
Hide Baseline Analysis Population Description
All randomized patients
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants 114 participants 225 participants
61.8  (13.4) 51.6  (12.5) 61.7  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 114 participants 225 participants
Female
44
  39.6%
36
  31.6%
80
  35.6%
Male
67
  60.4%
78
  68.4%
145
  64.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 114 participants 225 participants
Hispanic or Latino
3
   2.7%
6
   5.3%
9
   4.0%
Not Hispanic or Latino
108
  97.3%
107
  93.9%
215
  95.6%
Unknown or Not Reported
0
   0.0%
1
   0.9%
1
   0.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 114 participants 225 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   0.9%
2
   1.8%
3
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
31
  27.9%
26
  22.8%
57
  25.3%
White
79
  71.2%
85
  74.6%
164
  72.9%
More than one race
0
   0.0%
1
   0.9%
1
   0.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 111 participants 114 participants 225 participants
111
 100.0%
114
 100.0%
225
 100.0%
1.Primary Outcome
Title Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)
Hide Description To determine if oral Fe (Iron) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.
Time Frame Baseline (BL) and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with available change data
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description:

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Overall Number of Participants Analyzed 96 95
Mean (Standard Deviation)
Unit of Measure: mL/min
28.04  (212.75) 3.90  (190.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4570
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 21.03
Confidence Interval (2-Sided) 95%
-34.38 to 76.43
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)
Hide Description To determine the impact of oral Fe repletion on Submaximal exercise capacity as measured by 6MWT
Time Frame Measured at BL, week 8 and week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with available change data
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description:

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Overall Number of Participants Analyzed 111 114
Mean (Standard Deviation)
Unit of Measure: meters
8 weeks Number Analyzed 101 participants 97 participants
12.65  (95.89) 16.63  (83.20)
16 weeks Number Analyzed 97 participants 97 participants
10.76  (62.29) 30.94  (77.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments Change from Baseline to Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9487
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.77
Confidence Interval (2-Sided) 95%
-24.12 to 22.59
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments Change from Baseline to Week 16
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1921
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -12.67
Confidence Interval (2-Sided) 95%
-31.71 to 6.37
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Plasma NT-pro BNP
Hide Description To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)
Time Frame Measured at Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with available change data
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description:

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Overall Number of Participants Analyzed 98 98
Mean (Standard Deviation)
Unit of Measure: pg/ml
119.36  (1937.58) -70.88  (1256.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4296
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 182.43
Confidence Interval (2-Sided) 95%
-272.14 to 637.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score
Hide Description

To determine the impact of oral Fe repletion on Health Status: KCCQ.

KCCQ is a 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 for patients with congestive heart failure. It is a predictive tool that tracks how patients are doing if they have weakened heart muscle due to prior heart attacks, heart valve problems, viral infections, or other causes.

The KCCQs questions are used to calculate scores in ten domains. Physical Limitation, Symptom Stability, Frequency, Burden and Total Symptom. Social Limitation, Self-Efficacy, Quality of Life, and Clinical Summary. Overall summary: a combined measure of all the above.

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.

Time Frame Measured at Baseline, Week 8 and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with available change data
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description:

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Overall Number of Participants Analyzed 111 114
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 8 Number Analyzed 104 participants 103 participants
3.25  (16.91) 0.58  (13.63)
Week 16 Number Analyzed 100 participants 100 participants
3.42  (16.05) 4.11  (11.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments Change from baseline to week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0722
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.60
Confidence Interval (2-Sided) 95%
-0.33 to 7.52
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments Change from baseline to week 16
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6927
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
-2.83 to 4.24
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET
Hide Description To determine the impact of oral Fe repletion on O2 Uptake Kinetics as measured by CPET
Time Frame Measured at BL week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with available change data
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description:

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Overall Number of Participants Analyzed 71 62
Mean (Standard Deviation)
Unit of Measure: seconds
2.63  (13.31) -0.95  (13.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0643
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.56
Confidence Interval (2-Sided) 95%
-0.21 to 7.33
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2
Hide Description Change from baseline in Ventilatory Efficiency defined by Ve/VCO2 (carbon dioxide output) as measured by CPET
Time Frame Measured at BL week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with available change data
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description:

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

Overall Number of Participants Analyzed 96 95
Mean (Standard Deviation)
Unit of Measure: VE/VCO2 Slope
-0.48  (5.85) -1.31  (8.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Polysaccharide Iron Complex 150 mg, Placebo (for Polysaccharide Iron Complex 150 mg)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4006
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
-1.04 to 2.58
Estimation Comments [Not Specified]
Time Frame Randomization to Week 16
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Hide Arm/Group Description

oral Fe polysaccharide 150mg twice daily for 16 weeks

Polysaccharide Iron Complex 150 mg: Oral Iron

Oral placebo twice a day for 16 weeks

Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.

All-Cause Mortality
Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/111 (9.91%)      9/114 (7.89%)    
Gastrointestinal disorders     
Abdominal Pain  1  0/111 (0.00%)  0 1/114 (0.88%)  1
Gastrointestinal Pain  1  0/111 (0.00%)  0 1/114 (0.88%)  1
Melaena  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Rectal Haemorrhage  2  0/111 (0.00%)  0 1/114 (0.88%)  1
General disorders     
Non-Cardiac Chest Pain  2  2/111 (1.80%)  2 0/114 (0.00%)  0
Infections and infestations     
Bronchitis Viral  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Gastroenteritis Viral  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Pneumonia  2  4/111 (3.60%)  4 0/114 (0.00%)  0
Sepsis  2  1/111 (0.90%)  1 0/114 (0.00%)  0
Streptococcal Sepsis  2  1/111 (0.90%)  1 0/114 (0.00%)  0
Vestibular Neuronitis  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Injury, poisoning and procedural complications     
Abdominal Injury  2  1/111 (0.90%)  1 0/114 (0.00%)  0
Road Traffic Accident  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Norovirus Test Positive  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Investigations     
Liver Function Test Abnormal  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Metabolism and nutrition disorders     
Hyperosmolar Hyperglycaemic State  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Musculoskeletal and connective tissue disorders     
Musculoskeletal Chest Pain  2  1/111 (0.90%)  1 0/114 (0.00%)  0
Rhabdomyolysis  2  1/111 (0.90%)  1 0/114 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin Cancer  2  1/111 (0.90%)  1 0/114 (0.00%)  0
Psychiatric disorders     
Alcohol Withdrawal Syndrome  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Vascular disorders     
Hypertensive Crisis  2  1/111 (0.90%)  1 0/114 (0.00%)  0
Temporal Arteritis  2  0/111 (0.00%)  0 1/114 (0.88%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
2
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Polysaccharide Iron Complex 150 mg Placebo (for Polysaccharide Iron Complex 150 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/111 (16.22%)      24/114 (21.05%)    
Gastrointestinal disorders     
Abdominal Discomfort  1  0/111 (0.00%)  0 2/114 (1.75%)  2
Constipation  1  6/111 (5.41%)  8 4/114 (3.51%)  4
Diarrhoea  1  7/111 (6.31%)  7 4/114 (3.51%)  4
Nausea  1  1/111 (0.90%)  1 4/114 (3.51%)  4
General disorders     
Asthenia  1  1/111 (0.90%)  1 2/114 (1.75%)  2
Non-Cardiac Chest Pain  1  0/111 (0.00%)  0 2/114 (1.75%)  2
Injury, poisoning and procedural complications     
Fall  1  2/111 (1.80%)  2 0/114 (0.00%)  0
Metabolism and nutrition disorders     
Gout  1  1/111 (0.90%)  1 2/114 (1.75%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/111 (0.00%)  0 4/114 (3.51%)  4
Musculoskeletal Chest Pain  1  2/111 (1.80%)  2 0/114 (0.00%)  0
Pain in Extremity  1  0/111 (0.00%)  0 2/114 (1.75%)  2
Nervous system disorders     
Headache  1  2/111 (1.80%)  2 1/114 (0.88%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/111 (0.00%)  0 2/114 (1.75%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
To minimize the probability of inaccurate data in published materials, it is the policy of The Heart Failure Network (HFN) that all data and text considered for all papers, and all abstracts for presentation at scientific meetings, be submitted to the Publication & Presentation Subcommittee, the NHLBI Project Officer and the Coordinating Center for review and approval prior to presentation or publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Adrian Hernandez
Organization: Duke Clinical Research Institute
Phone: 919-668-7515
EMail: adrian.hernandez@duke.edu
Layout table for additonal information
Responsible Party: Adrian Hernandez, Duke University
ClinicalTrials.gov Identifier: NCT02188784     History of Changes
Other Study ID Numbers: Pro00054061
2U10HL084904 ( U.S. NIH Grant/Contract )
First Submitted: July 10, 2014
First Posted: July 14, 2014
Results First Submitted: December 30, 2016
Results First Posted: May 15, 2017
Last Update Posted: July 11, 2017