Clinical trial NCT05991128: The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Official title: The Effects of Ferric Derisomaltose Administered Before Hospital Discharge in Stabilised Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life: a Randomised, Parallel-group, Double-blind, Placebo Controlled Trial (COREVIVE-HFpEF)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure With Preserved Ejection Fraction
Iron Deficiencies
Acute Heart Failure
Keywords: Exercise capacity
Quality of life
Acute Heart Failure
Lead sponsor: China-Japan Friendship Hospital
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in 6-minute walking distance
timeFrame: Up to 3 days
Secondary outcomes:
measure: Change From Baseline in 6-minute walking distance
timeFrame: At 2 weeks, 4weeks after IV iron injection
measure: Change From Baseline in the KCCQ Clinical Summary Score
timeFrame: At 2 weeks, 4weeks after IV iron injection
measure: Change From Baseline in the EQ-5D-5L Questionnaire Indexed Value
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in NYHA Functional Class
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in PGA quality of life questionnaire
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in Concentration of hemoglobin (Hb)
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in proportion of reticulocyte (Ret%)
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in Concentration of ferritin
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in Concentration of transferrin saturation
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in Concentration of serum transferrin receptors (sTfR)
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in Left Ventricular Diastolic Function
timeFrame: At 2weeks, 4weeks after IV iron injection
measure: Change From Baseline in Left Atrial Diameter
timeFrame: At 2weeks, 4weeks after IV iron injection
Other outcomes:
measure: Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR)
timeFrame: At 3 days, 2weeks, 4weeks after IV iron injection
measure: A rise of high-sensitivity C-reaction protein (hs-CRP) levels from baseline
timeFrame: Up to 4 weeks
measure: Adverse Event after IV iron injection
timeFrame: Up to 4 weeks
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Chaoyang District
Study officials:
References: