Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure (IRONOUT)
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|ClinicalTrials.gov Identifier: NCT02188784|
Recruitment Status : Completed
First Posted : July 14, 2014
Results First Posted : May 15, 2017
Last Update Posted : July 11, 2017
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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
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Age >18 years
- Previous clinical diagnosis of heart failure with current New York Heart Association (NYHA) Class II-IV symptoms LVEF≤0.40 within 2 years prior to consent, and ≥3 months after a major change in cardiac status (i.e. CABG or CRT).
- Serum ferritin between 15-100 ng/ml or serum ferritin between 100-299 ng/ml with transferrin saturation <20%
- Hemoglobin 9.0-13.5 g/dL (males), 9-13.5 (females) at time of enrollment
Stable evidence-based medical therapy for HF (including beta-blocker and ACE-inhibitor/ARB unless previously deemed intolerant, and diuretics as necessary) with </= 100% change in dose for 30 days prior to randomization
a. Changes in diuretic dose guided by a patient-directed flexible dosing program are considered stable medical therapy
- Willingness to provide informed consent
- Presence of a neuromuscular, orthopedic or other non-cardiac condition that prevents the patient from exercise testing on a bicycle/treadmill ergometer and/or inability to achieve an RER ≥ 1.0 on screening/baseline CPET
- Severe renal dysfunction (eGFR< 20 ml/min/1.73m2)
- Severe liver disease (ALT or AST > 3x normal, alkaline phosphatase or bilirubin >2x normal)
- Gastrointestinal conditions known to impair Fe absorption (i.e. inflammatory bowel disease)
- Known active infection as defined by current use of oral or intravenous antimicrobial agents
- Documented active gastrointestinal bleeding
- Active malignancy other than non-melanoma skin cancers
- Anemia with known cause other than Fe deficiency or chronic disease
- Fe overload disorders (i.e. hemochromatosis or hemosiderosis)
- History of erythropoietin, IV or oral Fe therapy, or blood transfusion in previous 3 months.
- Current ventricular assist device
- Anticipated cardiac transplantation within the next 4 months
- Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
- Previous adverse reaction to study drug or other oral Fe preparation
- Known or anticipated pregnancy in the next 4 months
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
|Principal Investigator:||Adrian Hernandez, MD,MHS,FAHA||Duke University|
|Responsible Party:||Adrian Hernandez, MD, MHS, FAHA: Associate Professor of Medicine;Director, Outcomes & Health Services Research, Duke University|
|Other Study ID Numbers:||
2U10HL084904 ( U.S. NIH Grant/Contract )
|First Posted:||July 14, 2014 Key Record Dates|
|Results First Posted:||May 15, 2017|
|Last Update Posted:||July 11, 2017|
|Last Verified:||June 2017|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||After the study results have been published, site-specific participant data will be shared with sites upon request. Sites are expected to follow their specific institutional policies regarding sharing results with their participants.|
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