Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure

NCT02188784 | Completed Phase 3 Results DMC

• 2 other identifiers: Pro000540612U10HL084904
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 17

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.

Conditions

Chronic Heart Failure

Outcome Measures

Primary Outcomes (1)

• Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)

  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.

  Baseline (BL) and Week 16

Secondary Outcomes (5)

• Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)

  Measured at BL, week 8 and week 16

• Change in Plasma NT-pro BNP

  Measured at Baseline and Week 16

• Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score

  Measured at Baseline, Week 8 and Week 16

• Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET

  Measured at BL week 16

• Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2

  Measured at BL week 16

Study Arms (2)

Polysaccharide iron complex 150 mg

ACTIVE COMPARATOR

oral Fe polysaccharide 150mg twice daily for 16 weeks

Drug: Polysaccharide Iron Complex 150 mg

Placebo (for Polysaccharide Iron Complex 150 mg)

PLACEBO COMPARATOR

Oral placebo twice a day for 16 weeks

Drug: Placebo (for Polysaccharide Iron Complex)

Interventions

Polysaccharide Iron Complex 150 mg DRUG

Oral Iron

Also known as: Feramax 150 mg

Polysaccharide iron complex 150 mg

Placebo (for Polysaccharide Iron Complex) DRUG

Sugar capsule designed to mimic Polysaccharide Iron Complex.

Placebo (for Polysaccharide Iron Complex 150 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adrian Hernandez: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (17)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Louis University Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University Hospitals-Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Metor Health System

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17603, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Utah Hospitals and Clinics

Murray, Utah, 84107, United States

Location

The University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Related Publications (2)

• Lewis GD, Malhotra R, Hernandez AF, McNulty SE, Smith A, Felker GM, Tang WHW, LaRue SJ, Redfield MM, Semigran MJ, Givertz MM, Van Buren P, Whellan D, Anstrom KJ, Shah MR, Desvigne-Nickens P, Butler J, Braunwald E; NHLBI Heart Failure Clinical Research Network. Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial. JAMA. 2017 May 16;317(19):1958-1966. doi: 10.1001/jama.2017.5427.

  PMID: 28510680 DERIVED

• Lewis GD, Semigran MJ, Givertz MM, Malhotra R, Anstrom KJ, Hernandez AF, Shah MR, Braunwald E. Oral Iron Therapy for Heart Failure With Reduced Ejection Fraction: Design and Rationale for Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure. Circ Heart Fail. 2016 May;9(5):e000345. doi: 10.1161/CIRCHEARTFAILURE.115.000345.

  PMID: 27140203 DERIVED

MeSH Terms

Interventions

Niferex

Results Point of Contact

• Title: Dr. Adrian Hernandez
• Organization: Duke Clinical Research Institute

adrian.hernandez@duke.edu

919-668-7515

Study Officials

• Adrian Hernandez, MD,MHS,FAHA

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, MHS, FAHA: Associate Professor of Medicine;Director, Outcomes & Health Services Research

Study Record Dates

• First Submitted: July 10, 2014
• First Posted: July 14, 2014
• Study Start: September 3, 2014
• Primary Completion: April 6, 2016
• Study Completion: April 6, 2016
• Last Updated: July 11, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (17)