Impact of Intravenous Iron Repletion On Mechanisms of Exercise InTolerance in HFpEF (IRONMET-HFpEF)

NCT04945707 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2021P001501R01HL151841
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine if the correction of functional iron deficiency by administering a single dose of intravenous iron (ferric derimaltose or Monoferric®) in participants with heart failure with preserved ejection fraction (HFpEF) will improve exercise capacity as measured by the change in peak oxygen uptake (peak VO2) from baseline to 12 weeks.

Conditions

Iron-deficiency; Heart Failure With Preserved Ejection Fraction

Keywords

Heart Failure with Preserved Ejection Fraction; Iron Deficiency

Outcome Measures

Primary Outcomes (1)

• The change in peak oxygen uptake (peak VO2) from baseline to week 12 in HFpEF subjects with functional iron deficiency following a single dose of ferric derisomaltose or placebo.

  Peak VO2 measured by a maximal effort Cardiopulmonary Exercise Test (CPET)

  12 weeks

Secondary Outcomes (14)

• Change in resting pulmonary capillary wedge pressure (PCWP)

  Baseline to week 12

• Change in resting pulmonary artery pressure (PAP)

  Baseline to week 12

• Change in exercise pulmonary capillary wedge pressure/ cardiac output slope (PCWP/CO slope)

  Baseline to week 12

• Change in exercise pulmonary arterial pressure/ cardiac output slope (PAP/CO slope)

  Baseline to week 12

• Change in exercise peripheral oxygen extraction C(a-v)O2

  Baseline to week 12

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

Ferric derisomaltose (Monoferric®) 1000 mg X 1 (for subject \<50 kg, 20 mg/kg X1)

Drug: Ferric Derisomaltose 1000 Mg in 100 mL INTRAVENOUS SOLUTION [Monoferric]

Arm 2

PLACEBO COMPARATOR

Normal Saline

Drug: Placebo

Interventions

Ferric Derisomaltose 1000 Mg in 100 mL INTRAVENOUS SOLUTION [Monoferric] DRUG

Ferric derisomaltose (Monoferric) 1000 mg X1 (for subject \<50 kg, 20 mg/kg

Also known as: Monoferric

Arm 1

Placebo DRUG

Normal saline

Also known as: Normal Saline

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (≥18 years of age) able to provide informed consent.
• Stable heart failure (NYHA II-IV) for at least 4 weeks
• Heart Failure with Preserved left ventricular ejection fraction.(Left ventricular ejection fraction ≥ 50 % obtained within 6 months of informed consent.
• 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.
• Hemoglobin \>9.0 g/dL AND \<15.0 g/dL .
• Serum ferritin \<100 ng/mL OR 100 to 300 ng/mL with TSAT \<20%, but NOT ferritin \< 15 ng/mL.
• Demonstrate diminished exercise capacity: ≤ 75 % predicted peak VO2 as determined by a Cardiopulmonary Exercise Test (CPET) at the time of screening
• Perform a maximal effort CPET by achieving a Respiratory Exchange Ratio (RER) of ≥ 1.05

You may not qualify if:

• Current or planned intravenous iron supplementation. Iron-containing multivitamins (\<30 mgs /day) are permitted.
• Known hypersensitivity reaction to any component of ferric derisomaltose (Monofer®)
• 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.
• Documented active gastrointestinal bleeding
• Anemia with known cause other than iron deficiency or chronic disease
• Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 3 months of enrollment.
• 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.
• \. Planned surgical procedure during the trial period 13. Inability to return for follow up visits

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Massachusetts General Hospital: lead
• Pharmacosmos A/S: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 28510680 BACKGROUND

• Houstis NE, Eisman AS, Pappagianopoulos PP, Wooster L, Bailey CS, Wagner PD, Lewis GD. Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Diagnosing and Ranking Its Causes Using Personalized O2 Pathway Analysis. Circulation. 2018 Jan 9;137(2):148-161. doi: 10.1161/CIRCULATIONAHA.117.029058. Epub 2017 Oct 9.

  PMID: 28993402 BACKGROUND

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Iron Deficiencies

Interventions

ferric derisomaltose; Saline Solution

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Greg Lewis, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Greg Lewis, MD

CONTACT

617-724-9254; glewis@partners.org

Rajeev Malhotra, MD

CONTACT

rmalhotra@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Unblinded staff (clinical research nurse and unblinded investigator) prepare and administer study drug to subject and document and follow safety events. The subject is blinded. A tented covering will allow adequate viewing of the IV site, but outside of the view of the subject. All blinded staff will not be present during study drug infusion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: This is a double-blind, prospective, randomized, placebo-controlled study to assess exercise tolerance after iron repletion with a single dose of ferric derisomaltose (Monoferric®) IV compared to placebo in heart failure with preserved ejection fraction and with iron deficiency. Randomization will be stratified by sex and will be performed in permutated blocks of 4 to assure balanced group sizes

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: June 30, 2021
• Study Start: November 26, 2021
• Primary Completion: March 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)