Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure

Chronic Heart Failure Clinical Trial

— IRONOUT  

Official title:

Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02188784
• Other study ID #: Pro00054061
• Secondary ID: 2U10HL084904
• Status: Completed
• Phase: Phase 3
• First received: July 10, 2014
• Last updated: August 15, 2016
• Start date: August 2014
• Est. completion date: May 2016

Study information

• Verified date: August 2016
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure Exercise Testing) 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: May 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >18 years

2. Previous clinical diagnosis of heart failure with current 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• Polysaccharide Iron Complex 150 mg
Oral Iron
• Placebo (for Polysaccharide Iron Complex)
Sugar capsule designed to mimic Polysaccharide Iron Complex.

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	The University of Vermont - Fletcher Allen Health Care	Burlington	Vermont
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Metor Health System	Cleveland	Ohio
United States	University Hospitals-Case Medical Center	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	University of Utah Hospitals and Clinics	Murray	Utah
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
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

Sponsors (2)

Lead Sponsor	Collaborator
Adrian Hernandez	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 and Week 16	No
Secondary	Change in Submaximal exercise capacity	To determine the impact of oral Fe repletion on Submaximal exercise capacity: O2 uptake kinetics and ventilatory efficiency as measured by CPET and 6MWT	Measured at BL (6MWT, CPET), week 8 (6MWT) and week 16 (CPET, 6MWT)	No
Secondary	Change in Plasma NT-pro BNP	To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)	Measured at BL, week 8, week 16	No
Secondary	Change in Health Status: KCC Questionnaire (KCCQ)	To determine the impact of oral Fe repletion on Health Status: KCC Questionnaire (KCCQ)	Measured at BL and week 16	No