Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure

NCT ID: NCT02188784

Last Updated: 2017-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-03
• Study Completion Date: 2016-04-06

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.

Conditions

Chronic Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Polysaccharide iron complex 150 mg

oral Fe polysaccharide 150mg twice daily for 16 weeks

Group Type: ACTIVE_COMPARATOR

Polysaccharide Iron Complex 150 mg

Intervention Type: DRUG

Oral Iron

Placebo (for Polysaccharide Iron Complex 150 mg)

Oral placebo twice a day for 16 weeks

Group Type: PLACEBO_COMPARATOR

Placebo (for Polysaccharide Iron Complex)

Intervention Type: DRUG

Sugar capsule designed to mimic Polysaccharide Iron Complex.

Interventions

Polysaccharide Iron Complex 150 mg

Oral Iron

Intervention Type: DRUG

Placebo (for Polysaccharide Iron Complex)

Sugar capsule designed to mimic Polysaccharide Iron Complex.

Intervention Type: DRUG

Other Intervention Names

Feramax 150 mg

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Adrian Hernandez

OTHER

Sponsor Role: lead

Responsible Party

Adrian Hernandez

MD, MHS, FAHA: Associate Professor of Medicine;Director, Outcomes & Health Services Research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Adrian Hernandez, MD,MHS,FAHA

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Emory University School of Medicine

Atlanta, Georgia, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Saint Louis University Hospital

St Louis, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

University Hospitals-Case Medical Center

Cleveland, Ohio, United States

Metor Health System

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Lancaster General Hospital

Lancaster, Pennsylvania, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Utah Hospitals and Clinics

Murray, Utah, United States

The University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28510680 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27140203 (View on PubMed)

Other Identifiers

2U10HL084904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00054061

Identifier Type: -

Identifier Source: org_study_id