Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure (IRONOUT)
|ClinicalTrials.gov Identifier: NCT02188784|
Recruitment Status : Completed
First Posted : July 14, 2014
Results First Posted : May 15, 2017
Last Update Posted : July 11, 2017
The purpose of this study is to determine if oral iron (Fe) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 (oxygen uptake) 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.
Hypothesis: In a broad population of HFrEF patients with Fe deficiency, compared to oral placebo, therapy with oral Fe polysaccharide will be associated with improvement in functional capacity at 16 weeks as assessed by CPET.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Heart Failure||Drug: Polysaccharide Iron Complex 150 mg Drug: Placebo (for Polysaccharide Iron Complex)||Phase 3|
Therapeutic options to further improve functional capacity and symptoms in HF beyond neurohormonal antagonism are limited. Studies have demonstrated impaired oxidative capacity of skeletal muscle among HF patients, which may contribute to symptoms of breathlessness and persistent fatigue.
In addition to its role in erythropoiesis, iron (Fe) plays a critical role in skeletal muscle's oxygen (O2)-storage capacity (myoglobin) and systemic aerobic energy production. As Fe deficiency is common in patients with symptomatic HF, repletion of iron stores may improve submaximal exercise capacity among these patients beyond the effects on erythropoiesis.
While intravenous Fe repletion in HF patients with mild Fe-deficiency (i.e. Ferritin <100 or Ferritin 100-299 with transferrin saturation <20%) with or without anemia global well-being and functional status, oral Fe repletion has not been studied. Furthermore, the efficacy of oral Fe to replete iron stores in a similar population and its impact on functional capacity, measured objectively by peak VO2, remains unknown.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||225 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure|
|Actual Study Start Date :||September 3, 2014|
|Actual Primary Completion Date :||April 6, 2016|
|Actual Study Completion Date :||April 6, 2016|
Active Comparator: Polysaccharide iron complex 150 mg
oral Fe polysaccharide 150mg twice daily for 16 weeks
Drug: Polysaccharide Iron Complex 150 mg
Other Name: Feramax 150 mg
Placebo Comparator: Placebo (for Polysaccharide Iron Complex 150 mg)
Oral placebo twice a day for 16 weeks
Drug: Placebo (for Polysaccharide Iron Complex)
Sugar capsule designed to mimic Polysaccharide Iron Complex.
- Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption) [ Time Frame: Baseline (BL) and Week 16 ]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.
- Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT) [ Time Frame: Measured at BL, week 8 and week 16 ]To determine the impact of oral Fe repletion on Submaximal exercise capacity as measured by 6MWT
- Change in Plasma NT-pro BNP [ Time Frame: Measured at Baseline and Week 16 ]To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)
- Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score [ Time Frame: Measured at Baseline, Week 8 and Week 16 ]
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.
- Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET [ Time Frame: Measured at BL week 16 ]To determine the impact of oral Fe repletion on O2 Uptake Kinetics as measured by CPET
- Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2 [ Time Frame: Measured at BL week 16 ]Change from baseline in Ventilatory Efficiency defined by Ve/VCO2 (carbon dioxide output) as measured by CPET
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02188784
|United States, Georgia|
|Emory University School of Medicine|
|Atlanta, Georgia, United States, 30322|
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Saint Louis University Hospital|
|Saint Louis, Missouri, United States, 63110|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27705|
|United States, Ohio|
|University Hospitals-Case Medical Center|
|Cleveland, Ohio, United States, 44106|
|Metor Health System|
|Cleveland, Ohio, United States, 44109|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|Lancaster General Hospital|
|Lancaster, Pennsylvania, United States, 17603|
|Hospital of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|United States, Utah|
|University of Utah Hospitals and Clinics|
|Murray, Utah, United States, 84107|
|United States, Vermont|
|The University of Vermont - Fletcher Allen Health Care|
|Burlington, Vermont, United States, 05401|
|Principal Investigator:||Adrian Hernandez, MD,MHS,FAHA||Duke University|