Trial Outcomes & Findings for Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure (NCT NCT02188784)
NCT ID: NCT02188784
Last Updated: 2017-07-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
225 participants
Primary outcome timeframe
Baseline (BL) and Week 16
Results posted on
2017-07-11
Participant Flow
Participant milestones
| Measure |
Polysaccharide Iron Complex 150 mg
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Overall Study
STARTED
|
111
|
114
|
|
Overall Study
COMPLETED
|
102
|
101
|
|
Overall Study
NOT COMPLETED
|
9
|
13
|
Reasons for withdrawal
| Measure |
Polysaccharide Iron Complex 150 mg
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Overall Study
Death
|
3
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
3
|
9
|
|
Overall Study
Physician Decision
|
2
|
3
|
Baseline Characteristics
Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure
Baseline characteristics by cohort
| Measure |
Polysaccharide Iron Complex 150 mg
n=111 Participants
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=114 Participants
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
Total
n=225 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.8 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
51.6 years
STANDARD_DEVIATION 12.5 • n=7 Participants
|
61.7 years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
44 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
67 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
108 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
215 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
31 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
79 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
164 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
111 Participants
n=5 Participants
|
114 Participants
n=7 Participants
|
225 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (BL) and Week 16Population: All randomized patients with available change data
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.
Outcome measures
| Measure |
Polysaccharide Iron Complex 150 mg
n=96 Participants
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=95 Participants
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)
|
28.04 mL/min
Standard Deviation 212.75
|
3.90 mL/min
Standard Deviation 190.24
|
SECONDARY outcome
Timeframe: Measured at BL, week 8 and week 16Population: All randomized patients with available change data
To determine the impact of oral Fe repletion on Submaximal exercise capacity as measured by 6MWT
Outcome measures
| Measure |
Polysaccharide Iron Complex 150 mg
n=111 Participants
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=114 Participants
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)
8 weeks
|
12.65 meters
Standard Deviation 95.89
|
16.63 meters
Standard Deviation 83.20
|
|
Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)
16 weeks
|
10.76 meters
Standard Deviation 62.29
|
30.94 meters
Standard Deviation 77.33
|
SECONDARY outcome
Timeframe: Measured at Baseline and Week 16Population: All randomized patients with available change data
To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)
Outcome measures
| Measure |
Polysaccharide Iron Complex 150 mg
n=98 Participants
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=98 Participants
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Change in Plasma NT-pro BNP
|
119.36 pg/ml
Standard Deviation 1937.58
|
-70.88 pg/ml
Standard Deviation 1256.49
|
SECONDARY outcome
Timeframe: Measured at Baseline, Week 8 and Week 16Population: All randomized patients with available change data
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.
Outcome measures
| Measure |
Polysaccharide Iron Complex 150 mg
n=111 Participants
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=114 Participants
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score
Week 8
|
3.25 units on a scale
Standard Deviation 16.91
|
0.58 units on a scale
Standard Deviation 13.63
|
|
Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score
Week 16
|
3.42 units on a scale
Standard Deviation 16.05
|
4.11 units on a scale
Standard Deviation 11.80
|
SECONDARY outcome
Timeframe: Measured at BL week 16Population: All randomized patients with available change data
To determine the impact of oral Fe repletion on O2 Uptake Kinetics as measured by CPET
Outcome measures
| Measure |
Polysaccharide Iron Complex 150 mg
n=71 Participants
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=62 Participants
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET
|
2.63 seconds
Standard Deviation 13.31
|
-0.95 seconds
Standard Deviation 13.29
|
SECONDARY outcome
Timeframe: Measured at BL week 16Population: All randomized patients with available change data
Change from baseline in Ventilatory Efficiency defined by Ve/VCO2 (carbon dioxide output) as measured by CPET
Outcome measures
| Measure |
Polysaccharide Iron Complex 150 mg
n=96 Participants
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=95 Participants
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2
|
-0.48 VE/VCO2 Slope
Standard Deviation 5.85
|
-1.31 VE/VCO2 Slope
Standard Deviation 8.85
|
Adverse Events
Polysaccharide Iron Complex 150 mg
Serious events: 11 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo (for Polysaccharide Iron Complex 150 mg)
Serious events: 9 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Polysaccharide Iron Complex 150 mg
n=111 participants at risk
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=114 participants at risk
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Gastrointestinal disorders
Gastrointestinal Pain
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
General disorders
Non-Cardiac Chest Pain
|
1.8%
2/111 • Number of events 2 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Infections and infestations
Bronchitis Viral
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Infections and infestations
Gastroenteritis Viral
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Infections and infestations
Pneumonia
|
3.6%
4/111 • Number of events 4 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Infections and infestations
Sepsis
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Infections and infestations
Streptococcal Sepsis
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Infections and infestations
Vestibular Neuronitis
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Injury, poisoning and procedural complications
Abdominal Injury
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Injury, poisoning and procedural complications
Road Traffic Accident
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Investigations
Liver Function Test Abnormal
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Injury, poisoning and procedural complications
Norovirus Test Positive
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Metabolism and nutrition disorders
Hyperosmolar Hyperglycaemic State
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Cancer
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Psychiatric disorders
Alcohol Withdrawal Syndrome
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Vascular disorders
Hypertensive Crisis
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Vascular disorders
Temporal Arteritis
|
0.00%
0/111 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
Other adverse events
| Measure |
Polysaccharide Iron Complex 150 mg
n=111 participants at risk
oral Fe polysaccharide 150mg twice daily for 16 weeks
Polysaccharide Iron Complex 150 mg: Oral Iron
|
Placebo (for Polysaccharide Iron Complex 150 mg)
n=114 participants at risk
Oral placebo twice a day for 16 weeks
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/111 • Randomization to Week 16
|
1.8%
2/114 • Number of events 2 • Randomization to Week 16
|
|
Gastrointestinal disorders
Constipation
|
5.4%
6/111 • Number of events 8 • Randomization to Week 16
|
3.5%
4/114 • Number of events 4 • Randomization to Week 16
|
|
Gastrointestinal disorders
Diarrhoea
|
6.3%
7/111 • Number of events 7 • Randomization to Week 16
|
3.5%
4/114 • Number of events 4 • Randomization to Week 16
|
|
Gastrointestinal disorders
Nausea
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
3.5%
4/114 • Number of events 4 • Randomization to Week 16
|
|
General disorders
Asthenia
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
1.8%
2/114 • Number of events 2 • Randomization to Week 16
|
|
General disorders
Non-Cardiac Chest Pain
|
0.00%
0/111 • Randomization to Week 16
|
1.8%
2/114 • Number of events 2 • Randomization to Week 16
|
|
Injury, poisoning and procedural complications
Fall
|
1.8%
2/111 • Number of events 2 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Metabolism and nutrition disorders
Gout
|
0.90%
1/111 • Number of events 1 • Randomization to Week 16
|
1.8%
2/114 • Number of events 2 • Randomization to Week 16
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/111 • Randomization to Week 16
|
3.5%
4/114 • Number of events 4 • Randomization to Week 16
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
1.8%
2/111 • Number of events 2 • Randomization to Week 16
|
0.00%
0/114 • Randomization to Week 16
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.00%
0/111 • Randomization to Week 16
|
1.8%
2/114 • Number of events 2 • Randomization to Week 16
|
|
Nervous system disorders
Headache
|
1.8%
2/111 • Number of events 2 • Randomization to Week 16
|
0.88%
1/114 • Number of events 1 • Randomization to Week 16
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/111 • Randomization to Week 16
|
1.8%
2/114 • Number of events 2 • Randomization to Week 16
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER