Effect of intravenous iron on exercise tolerance in heart failure patients

A Double-blind,Randomized, Placebo-controlled Study to Assess Exercise Tolerance After Iron Repletion With Ferric Derisomaltose (Monoferric®) IV Compared to Placebo in Heart Failure With Preserved Ejection Fraction and With Iron Deficiency.

This study is testing if a single dose of intravenous iron can help people with heart failure and low iron levels exercise better over 12 weeks.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT04945707 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate whether administering a single dose of intravenous iron (ferric derisomaltose) can improve exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) who also have functional iron deficiency. It is a double-blind, randomized, placebo-controlled trial involving 66 participants who will undergo baseline assessments including cardiopulmonary exercise testing and echocardiograms. Participants will be randomly assigned to receive either the iron treatment or a placebo, and their exercise capacity will be measured by changes in peak oxygen uptake over 12 weeks.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with stable heart failure (NYHA II-IV) and documented functional iron deficiency.

Not a fit: Patients with heart failure not meeting the criteria for preserved ejection fraction or those without functional iron deficiency may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly enhance exercise capacity and overall quality of life for patients with HFpEF and iron deficiency.

How similar studies have performed: Previous studies have indicated potential benefits of iron repletion in heart failure patients, suggesting this approach may be promising.

Eligibility criteria

Inclusion Criteria:

1. Adult (≥18 years of age) able to provide informed consent.
2. Stable heart failure (NYHA II-IV) for at least 4 weeks
3. Heart Failure with Preserved left ventricular ejection fraction.(Left ventricular ejection fraction ≥ 50 % obtained within 6 months of informed consent.
4. NT-proBNP ≥ 125 pg/mL without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at the time of sample collection, NT-proBNP must be ≥ 250 pg/mL OR patients must have a history of pulmonary capillary wedge pressure ≥ 15 mm Hg during rest or the slope of pulmonary capillary wedge pressure to cardiac output (PCWP/CO) ≥ 2.0 mmHg/L/min during upright exercise (Eisman et al., Circ Heart Fail. 2018 May;11(5):e004750.).OR subjects must have a heart failure hospitalization within the last 12 months prior to screening OR Chronic diastolic dysfunction on echocardiography as evidenced by: Left Atrial Enlargement (LAE): LA diameter ≥ 3.8cm in women, ≥ 4.0 cm in men or LA length ≥ 5.0 cm or LA area ≥ 20 cm2 OR LA volume ≥ 55mL or LA volume index ≥ 29ml/m2 or Left Ventricular Hypertrophy (LVH): septal thickness or posterior wall thickness ≥ 1.1 cm OR For patients in sinus rhythm: E/e' ratio ≥15 at septal annulus, or E/e' ratio ³13 at lateral annulus, or average E/e' ratio ³14. For patients in atrial fibrillation: E/e' ≥ 11 at the septal annulus.
5. Hemoglobin \>9.0 g/dL AND \<15.0 g/dL .
6. Serum ferritin \<100 ng/mL OR 100 to 300 ng/mL with TSAT \<20%, but NOT ferritin \< 15 ng/mL.
7. Demonstrate diminished exercise capacity: ≤ 75 % predicted peak VO2 as determined by a Cardiopulmonary Exercise Test (CPET) at the time of screening
8. Perform a maximal effort CPET by achieving a Respiratory Exchange Ratio (RER) of ≥ 1.05

Exclusion Criteria:

1. Current or planned intravenous iron supplementation. Iron-containing multivitamins (\<30 mgs /day) are permitted.
2. Known hypersensitivity reaction to any component of ferric derisomaltose (Monofer®)
3. History of acquired iron overload (e.g. hemochromatosis), or the recent receipt (within 3 months) of erythropoietin stimulating agent, IV iron therapy, or blood transfusion.
4. Documented active gastrointestinal bleeding
5. Anemia with known cause other than iron deficiency or chronic disease
6. Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 3 months of enrollment.

7 Presence of any condition that precludes exercise testing such as:

a. Claudication that limits exertion b. Uncontrolled bradyarrhythmia or tachyarrhythmia (according to Investigator judgment, pacemaker treatment is allowed as long as the same pacing mode/activity can be used at baseline and follow-up CPET) c. Clinically significant musculoskeletal disease or orthopedic conditions that limit the ability to perform the CPET (e.g., arthritis or injury in the foot, leg, knee or hip) d. Severe obesity (BMI \> 50.0 kg/m2) e. Any other non-heart failure condition that, in the opinion of the Investigator, that is the primary limitation to exercise. 8. Severe renal dysfunction (eGFR\< 20 ml/min/1.73m2) 9. Severe liver disease (ALT or AST \> 3x upper limit of normal, alkaline phosphatase or bilirubin \>2x upper limit of normal) 10. Active malignancy other than non-melanoma skin cancers 11. Female participant of child-bearing potential who is pregnant, lactating, or not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.

12\. Planned surgical procedure during the trial period 13. Inability to return for follow up visits

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Greg Lewis, MD — Massachusetts General Hospital
• Study coordinator: Greg Lewis, MD

Conditions: Iron-deficiency, Heart Failure With Preserved Ejection Fraction, Heart Failure with Preserved Ejection Fraction, Iron Deficiency