The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life (COREVIVE-HFpEF)

China-Japan Friendship Hospital

Status and phase: Enrolling; Phase 4

Conditions: Iron Deficiencies; Heart Failure With Preserved Ejection Fraction; Acute Heart Failure

Treatments: Drug: Ferric derisomaltose; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05991128

Monofer-HFpEF

Details and patient eligibility

About

This study will address whether the additional use of Ferric Derisomaltose on top of standard care will improve exercise capacity and quality of life in patients with acute heart failure and iron deficiency. One group of participants will receive treatment with Ferric Derisomaltose and the other group will receive normal saline 0.9% as placebo.

Full description

Acute heart failure is very common medical problem. Despite many clinical trials conducted to date in these patients, the rates of adverse outcomes remain very high. Previous comorbidities may account for it. Approximately 80% of patients hospitalized with AHF suffered from a combination of iron deficiency. A decline in exercise capacity may occur under this condition. Some research studies have suggested that giving CHF patients intravenous iron improves symptoms in the short term. It is unknown, however, whether correcting iron deficiency is beneficial to patients with AHF to improve excise capacity and whether it improves quality of life and accelerate recovery from acute duration. This study will help us answer these key questions.

This is an investigator-initiated, randomised, parallel group, double-blind, placebo-controlled trial, evaluating the excise capacity improvement of using ferric derimaltose versus placebo in hospitalized patients with acute heart failure with preserved ejection fraction before discharge.

Participants will be assessed daily using 6-minute walking test after IV iron injection until discharge from hospital, especially focus on the change from baseline to the 3rd day. Some questionnaire are also conducted to evaluate the self-reported status. Participants will be followed up at 2 weeks and 4 weeks.

The primary and secondary endpoints will be examined in subgroups predefined by baseline variables reflecting demography, Hb level, etiology of HF, left ventricular ejection fraction, natriuretic peptide, index of iron metabolism, eGFR and others.

Enrollment: 170 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥18 years.

2. Clinical diagnosis of heart failure with preserved ejection fraction (HFpEF), defined as documented 2-dimensional echocardiography left ventricular ejection fraction (LVEF) ≥50% before randomization.

3. Currently hospitalized for an episode of acute heart failure (AHF) where AHF was the primary reason for hospitalization, New York Heart Association (NYHA) class II - IV.N-terminal pro brain natriuretic peptide (NT-proBNP) ≥300 or brain natriuretic peptide (BNP) ≥100 pg/mL in sinus rhythm, or NT-proBNP≥600 or BNP ≥200 pg/mL in atrial fibrillation prior to randomization

4. Reaching hemodynamic stability after standard treatment (if tolerated, initiate four pillars of guideline-directed medical therapies). All of the following (i.e., items a to c) must apply:

   1. Systolic blood pressure≥100mmHg, without symptoms of hypotension;
   2. Stop using intravenous diuretics;
   3. Neither intravenous inotropic drugs or vasodilators were used (including nitrates).

5. Subject is iron deficient defined as serum ferritin <100 ng/mL or 100 ng/mL ≤ serum ferritin ≤299 ng/mL if TSAT <20%.

6. Able and willing to provide informed consent and accomplish 6 minutes-walking test.

Exclusion criteria

1. Haematological criteria: ferritin >400ug/L; haemoglobin <9.0 g/dL, or >13.5 g/dL (for female), 14.5g/dL (for male).
2. Renal dialysis or MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2
3. Body weight<35kg at randomization.
4. Heart failure was secondary to valvular diseases or congenital heart diseases.
5. History of acquired iron overload or hemochromatosis (or first-degree relative of haemochromatosis)
6. Known hypersensitivity reaction to any component of ferric derisomaltose (Monofer®) or any of its excipients (water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment)).
7. Non-iron deficiency anaemia.
8. Already receiving erythropoiesis stimulating agents (ESA) or other iron supplements in previous 4 weeks prior to randomization.
9. Active infection (defined as currently treated with oral or intravenous antibiotics), bleeding (gastrointestinal haemorrhagia, menorrhagia, history of peptic ulcer with no evidence of healing or inflammatory bowel disease) and history of malignant tumor.
10. Any of the following diseases that hinders exercise testing: severe musculoskeletal disease, unstable angina, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled slow or rapid arrhythmia (mean heart rate> 100 beats / min at rest).
11. Known positive HBsAg and/or HCV RNA; known HIV positivity; chronic liver disease (including active hepatitis), hepatic sclerosis, ALT or AST > 3x upper limit of normal.
12. Within 3 months of any of the following: acute myocardial infarction (AMI) or acute coronary syndrome (ACS), transient ischemic attack (TIA) or stroke, uncontrolled hypertension.
13. Revascularization therapy (coronary artery bypass grafting, percutaneous intervention, or major surgery) in the past 3 months; or planning cardiac surgery or revascularization.

14.6 minutes-walking distance>500m at baseline. 15.Treated with long-term oral high-dose or steroid-immunosuppression therapy. 16.Investigator considers a possible alternative diagnosis to explain the patient's HF symptoms: severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease (COPD).

17.Subject is pregnant (e.g., positive human chorionic gonadotropin test) or breast feeding.

18.Untreated hypothyroidism. 19.Currently enrolled in any other investigational device or drug study <30 days prior to screening or received other investigational agent(s).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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170 participants in 2 patient groups, including a placebo group

Ferric derisomaltose

Experimental group

Description:

Iron to be administered as ferric derisomaltose. The treatment dose (mL) to be administered will be determined by the patient's body weight and haemoglobin (Hb) value. Where Hb ≥10 g/dL, dosage according to body weight is as follows: Body weight \<50 kg: 20 mg/kg; Body weight 50 to \<70 kg: 1000 mg; Body weight ≥70 kg: 20 mg/kg up to a maximum of 1500 mg. Where Hb \<10 g/dL, dosage according to body weight is as follows: Body weight \<50 kg: 20 mg/kg; Body weight 50 to \<70 kg: 20 mg/kg; Body weight ≥70 kg: 20 mg/kg up to a maximum of 2000 mg. Infused over a minimum of 15mins for doses up to and including 1000mg, and a minimum of 30 mins for doses \>1000mg

Treatment:

Drug: Ferric derisomaltose

Placebo

Placebo Comparator group

Description:

Participants in this arm will receive normal saline 0.9% in analogy to treatment arm.

Treatment:

Drug: Placebo