Heart Failure, Heart Failure With Preserved Ejection Fraction (HFPEF), Heart Failure With Reduced Ejection Fraction (HFrEF), Iron Deficiency, Iron-deficiency Anemia (IDA)
Conditions
Keywords
Intravenous iron, Oral iron, Ferric carboxymaltose, Ferrous sulfate, Transferrin saturation (TSAT), Functional iron deficiency, 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), Quality of life, Randomized controlled trial, Congestive heart failure, HFpEF, HFrEF
Brief summary
The goal of this clinical trial is to learn which iron treatment works better for adults with congestive heart failure and low iron levels: intravenous (IV) iron given through a vein or oral (PO) iron taken by mouth. Participants must have heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) and a transferrin-saturation (TSAT) level below 20 percent. The main questions the study will answer are: 1. Does IV iron raise walking distance on a 6-minute walk test more than oral iron after 24 weeks? 2. Does IV iron improve symptoms and quality of life more than oral iron? 3. How do the two treatments compare for safety, side effects, and hospital readmissions/ mortality? Researchers will compare IV ferric carboxymaltose with oral ferrous sulfate to see which option helps people feel and function better. What participants will do * Be randomly assigned by (like flipping a coin) to IV iron or oral iron. * Receive either a one-time IV iron infusion (with possible repeat at 12 weeks) or take iron pills twice each day for 24 weeks. * Visit the infusion clinic at 6 weeks for second dose of IV iron if needed. * Visit the clinic at 12 weeks for a follow-up to gather follow-up data including 1. A 6-minute walk test 2. Brief symptom and quality-of-life surveys 3. Blood tests to measure serum iron, ferritin, and transferrin saturation This study will help doctors decide whether IV or oral iron is the safer, more effective way to treat iron deficiency in people with heart failure in our local community.
Interventions
DRUGFerric Carboxymaltose
Intravenous infusion of 1 gram FCM during index hospital stay, followed by a second dose at Week 6 (1,000 mg if \> 70 kg or 500 mg if ≤ 70 kg).
DRUGFerrous Sulfate
Oral administration of one 150 mg capsule every 48 hours for 12 weeks.
Sponsors
Syed Hamza Mufarrih
American Regent, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Investigators and participants know group assignment. 6-minute walk test staff, data analysts, and clinical endpoint adjudicators remain blinded.
Intervention model description
Randomized, 1:1, parallel-group, open-label PROBE design comparing IV ferric carboxymaltose with oral ferrous sulfate in adults with heart failure and TSAT \< 20 %.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * BMI ≥18.0 kg/m² * Hemoglobin: \> 9 g/dL and \<14 g/dL for men \> 9 g/dL and \<13 g/dL for women * Diagnosed with Congestive Heart failure: HFrEF: EF ≤40% in any recent echocardiogram HFpEF: EF ≥50-55% without any prior EF ≤40%, and evidence of diastolic dysfunction per ASE/EACVI 2023 criteria-defined as either grade ≥2 or ≥2 supporting echo parameters (septal e' \<7 cm/sec or lateral e' \<10 cm/sec, E/e' ≥15, TR velocity \>2.8 m/s, LA volume index ≥34 mL/m², LV septal or posterior wall thickness ≥1.2 cm, or LA area ≥20 cm² / diameter ≥3.8 cm. * Documented elevated NT-proBNP based on BMI and rhythm: BMI \<35: ≥220 pg/mL (NSR) or ≥660 pg/mL (A-Fib) BMI ≥35: ≥125 pg/mL (NSR) or ≥375 pg/mL (A-Fib) * NYHA Class II-IV * Transferrin saturation (TSAT) \<20% * Hemoglobin \<14 g/dL for men, \< 13 g/dL for women. * Stable on heart failure therapy for ≥2-4 weeks * Currently prescribed a diuretic at home * Ambulatory (able to walk \>20 ft with minimal assistance) * Willing and able to give informed consent
Exclusion criteria
* Received IV iron, ESA, or blood transfusion within the last 6-12 months * Received high-dose oral iron (\>100 mg/day in past 7 days) * Severe renal impairment (eGFR \<15 mL/min/1.73 m² or on dialysis) * Patients with known cirrhosis or transaminitis with AST \>141 or ALT \>112 IU/L * Active bleeding or known bleeding disorder * Recent cardiac surgery, myocardial infarction, or stroke within past 3 months * Active infection, defined as any systemic or deep-seated infection (e.g., bacteremia, sepsis, osteomyelitis, or infections requiring IV antibiotics or hospitalization) at the time of screening. * Active malignancy or undergoing chemotherapy/radiotherapy * Vitamin B12 or folate deficiency (unless corrected prior to enrollment) * Chronic liver disease (with LFTs \>3× upper limit of normal) * Pregnant or breastfeeding women or those not using effective contraception * Lacks capacity to consent or unable to comply with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6-Minute Walk Distance | Baseline and 12 weeks | Change in distance (in meters) walked during the 6-minute walk test from baseline to 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in NYHA Functional Class | Baseline and 12 weeks | Change in New York Heart Association (NYHA) class from baseline to 12 weeks. |
| Change in Quality of Life | Baseline and 12 weeks | Change in patient-reported quality of life scores as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) |
| Change in Iron Stores | Baseline and 12 weeks | Change in iron parameters including serum ferritin, serum iron, and transferrin saturation from baseline to 12 weeks. |
| All-Cause Mortality | Through 12 weeks | Death from any cause during the 12-week study period. |
| Heart Failure Readmissions | Through 12 weeks | Number of heart failure-related hospital readmissions within 12 weeks. |
| Major Adverse Cardiac Events (MACE) | Through 12 weeks | Composite of cardiovascular death, myocardial infarction, or stroke during the 12-week study period. |
| Adverse Events Related to Study Drug | Through 12 weeks | Frequency of reported adverse effects attributed to either ferric carboxymaltose or oral ferrous sulfate during the study period. |
Countries
United States
Outcome results
None listed