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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
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Adrian Hernandez, Duke University

Tracking Information
First Submitted Date  ICMJE July 10, 2014
First Posted Date  ICMJE July 14, 2014
Results First Submitted Date  ICMJE December 30, 2016
Results First Posted Date  ICMJE May 15, 2017
Last Update Posted Date July 11, 2017
Actual Study Start Date  ICMJE September 3, 2014
Actual Primary Completion Date April 6, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 11, 2014)
Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption) [ Time Frame: Baseline 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 History Complete list of historical versions of study NCT02188784 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2017)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2014)
  • Change in Submaximal exercise capacity [ Time Frame: Measured at BL (6MWT, CPET), week 8 (6MWT) and week 16 (CPET, 6MWT) ]
    To determine the impact of oral Fe repletion on Submaximal exercise capacity: O2 uptake kinetics and ventilatory efficiency as measured by CPET and 6MWT
  • Change in Plasma NT-pro BNP [ Time Frame: Measured at BL, week 8, 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: KCC Questionnaire (KCCQ) [ Time Frame: Measured at BL and week 16 ]
    To determine the impact of oral Fe repletion on Health Status: KCC Questionnaire (KCCQ)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure
Official Title  ICMJE Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure
Brief Summary

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.

Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Heart Failure
Intervention  ICMJE
  • Drug: Polysaccharide Iron Complex 150 mg
    Oral Iron
    Other Name: Feramax 150 mg
  • Drug: Placebo (for Polysaccharide Iron Complex)
    Sugar capsule designed to mimic Polysaccharide Iron Complex.
Study Arms  ICMJE
  • Active Comparator: Polysaccharide iron complex 150 mg
    oral Fe polysaccharide 150mg twice daily for 16 weeks
    Intervention: Drug: Polysaccharide Iron Complex 150 mg
  • Placebo Comparator: Placebo (for Polysaccharide Iron Complex 150 mg)
    Oral placebo twice a day for 16 weeks
    Intervention: Drug: Placebo (for Polysaccharide Iron Complex)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 15, 2016)
225
Original Estimated Enrollment  ICMJE
 (submitted: July 11, 2014)
220
Actual Study Completion Date  ICMJE April 6, 2016
Actual Primary Completion Date April 6, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age >18 years
  2. 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).
  3. Serum ferritin between 15-100 ng/ml or serum ferritin between 100-299 ng/ml with transferrin saturation <20%
  4. Hemoglobin 9.0-13.5 g/dL (males), 9-13.5 (females) at time of enrollment
  5. 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

  6. Willingness to provide informed consent

Exclusion Criteria:

  1. 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
  2. Severe renal dysfunction (eGFR< 20 ml/min/1.73m2)
  3. Severe liver disease (ALT or AST > 3x normal, alkaline phosphatase or bilirubin >2x normal)
  4. Gastrointestinal conditions known to impair Fe absorption (i.e. inflammatory bowel disease)
  5. Known active infection as defined by current use of oral or intravenous antimicrobial agents
  6. Documented active gastrointestinal bleeding
  7. Active malignancy other than non-melanoma skin cancers
  8. Anemia with known cause other than Fe deficiency or chronic disease
  9. Fe overload disorders (i.e. hemochromatosis or hemosiderosis)
  10. History of erythropoietin, IV or oral Fe therapy, or blood transfusion in previous 3 months.
  11. Current ventricular assist device
  12. Anticipated cardiac transplantation within the next 4 months
  13. Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
  14. Previous adverse reaction to study drug or other oral Fe preparation
  15. Known or anticipated pregnancy in the next 4 months
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02188784
Other Study ID Numbers  ICMJE Pro00054061
2U10HL084904 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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.
Responsible Party Adrian Hernandez, Duke University
Study Sponsor  ICMJE Adrian Hernandez
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Adrian Hernandez, MD,MHS,FAHA Duke University
PRS Account Duke University
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP