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Ferric Carboxymaltose to Improve Skeletal Muscle Metabolism in Heart Failure Patients With Functional Iron Deficiency

Phase 2
Terminated
Conditions
Iron-deficiency
Interventions
Drug: Placebo
Device: 31P MRS/MRI
Registration Number
NCT03218384
Lead Sponsor
NYU Langone Health
Brief Summary

The purpose of this study is to better understand how body levels of iron affect the ability to exercise in patients with heart failure (HF).

Heart failure is a condition in which abnormal pumping action of the heart reduces the flow of blood to the body. Patients with heart failure may feel shortness of breath or leg fatigue when they exercise. Iron is an essential nutrient in the diet. In heart failure patients, low body levels of iron might increase shortness of breath and fatigue.

Detailed Description

The purpose of this prospective, double blind parallel group randomized study is to compare the effects of ferric carboxymaltose vs. placebo on skeletal muscle mitochondrial oxidative capacity, submaximal exercise tolerance, and health-related quality of life in non-anemic Heart Failure (HF) patients with functional iron deficiency.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
20
Inclusion Criteria
  • Symptomatic NYHA Class II-III heart failure >3 months
  • Guideline-recommended heart failure treatment for > 3 months
  • Hemoglobin >13 g/dl for men and >12 g/dl for women
  • Functional iron deficiency (defined as serum ferritin level <100 ng/ml or between 100 and 299 ng/ml with transferrin saturation <20%)
  • Left ventricular ejection fraction <40%, or left ventricular ejection fraction ≥40% with left atrial enlargement (left atrial volume index >28 ml/m2) and/or left ventricular hypertrophy (left ventricular mass index >95 g/m2 (women) or >115 g/m2 (men) determined by echocardiogram within last 24 months.
  • Able and willing to provide written informed consent
Exclusion Criteria
  • Presence of implantable defibrillator, permanent pacemaker, other metal implant not compatible with 3TMRS/MRI, or other contraindication to 3T MRS/MRI procedures
  • Heart failure due to infiltrative cardiomyopathy, restrictive cardiomyopathy, or hypertrophic cardiomyopathy
  • Weight <50 kg or >120 kg
  • Coronary or cerebral atherothrombotic events in the past 6 months
  • Hospitalization of emergency room visit for heart failure within past 3 months
  • ICD shock in last 3 months
  • Known peripheral artery disease or ankle-brachial index <0.9 at screening visit
  • Exercise primarily limited by angina, lung disease or neuromuscular disease
  • Systolic blood pressure <100 or >160 mmHg
  • Heart rate <50 or >110 min-1
  • Estimated glomerular filtration rate <30 ml/min
  • Liver function tests >3 times upper limit of normal
  • Serum phosphate below normal limit
  • Pregnant or breast-feeding women
  • Women of child-bearing potential unwilling to use recommended contraception methods during the study
  • Treatment with oral iron supplements (except multivitamins) in past year
  • Treatment with intravenous iron in past year
  • Treatment with erythropoiesis stimulating agents in the past year
  • Known intolerance of intravenous iron
  • History of anaphylaxis
  • Participation in another clinical trial within last 30 days.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboHF patients with functional iron deficiency assigned to receive one-time dose of Placebo (saline injection). Participants will undergo serial assessment before and 4 weeks after study drug administration.
Ferric Carboxymaltose31P MRS/MRIHF patients with functional iron deficiency assigned to receive one-time dose of Ferric Carboxymaltose 750 mg. Participants will undergo serial assessment before and 4 weeks after study drug administration
Placebo31P MRS/MRIHF patients with functional iron deficiency assigned to receive one-time dose of Placebo (saline injection). Participants will undergo serial assessment before and 4 weeks after study drug administration.
Ferric CarboxymaltoseFerric CarboxymaltoseHF patients with functional iron deficiency assigned to receive one-time dose of Ferric Carboxymaltose 750 mg. Participants will undergo serial assessment before and 4 weeks after study drug administration
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Post-Exercise Phosphocreatine Recovery TimeBaseline, Week 4

Post-exercise phosphocreatine recovery time (in seconds) will be used to assess mitochondrial oxidative capacity. It is measured non-invasively with 31P-magnetic resonance spectroscopy.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Kansas City Cardiomyopathy Questionnaire ScoreBaseline, Week 4

23-item self-assessment of symptoms, physical and social limitations, and quality of life in patients with heart failure. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best. The total score ranges from 0-100, with higher scores indicating better health status. An increase in scores indicates health status improved during the observational period.

Change From Baseline in Hemoglobin LevelsBaseline, Week 4

Hemoglobin is a protein in red blood cells that carries oxygen. Hemoglobin levels (g/dL) were measured in laboratory analyses using patient blood samples.

Change From Baseline in 6-Minute Walk Test DistanceBaseline, Week 4

The 6-minute walk test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes.

Change From Baseline in Serum Ferritin LevelsBaseline, Week 4

Ferritin is a blood protein that contains iron. Serum ferritin levels (ng/ml) were measured in laboratory analyses using patient blood samples.

Change From Baseline in Transferrin SaturationBaseline, Week 4

Transferrin saturation, measured as a percentage, is the value of serum iron divided by the total iron-binding capacity of the available transferrin. Transferrin saturation was measured in laboratory analyses using patient blood samples.

Trial Locations

Locations (1)

New York University School of Medicine

🇺🇸

New York, New York, United States

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