A study to compare the use of ferric carboxymaltose with placebo in patients with acute heart failure and iron deficiency
- Conditions
- Acute heart failure with iron deficiencyMedDRA version: 20.0Level: SOCClassification code 10007541Term: Cardiac disordersSystem Organ Class: 10007541 - Cardiac disordersMedDRA version: 20.0Level: LLTClassification code 10000803Term: Acute heart failureSystem Organ Class: 10007541 - Cardiac disordersMedDRA version: 20.0Level: PTClassification code 10022970Term: Iron deficiencySystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-001467-36-PL
- Lead Sponsor
- Vifor (International) Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 650
1 Currently hospitalised for an episode of acute heart failure (AHF) where AHF was the primary reason for hospitalisation. All of the following (i.e., items a to d) must apply:
a. Upon admission for the AHF episode, persistent dyspnoea at rest in a recumbent sitting position (30-45°) or with minimal exertion
b. Upon or during the AHF admission, at least two (2) of the following clinical findings were present:
i. Congestion on chest x-ray
ii. Rales on chest auscultation
iii. Oedema =1+ on a 0-3+ scale, indicating indentation of skin with mild digital pressure that requires 10 or more seconds to resolve in any dependent area including extremities or sacral region
iv. Elevated jugular venous pressure (=8 cm H2O)
c Natriuretic peptide levels, measured =24 hours of the AHF admission must have been:
i. Brain natriuretic peptide (BNP) =400 pg/mL or N-terminal-pro-brain natriuretic peptide (NT-proBNP) =1,600 pg/mL or
ii. BNP =600 pg/mL or NT-proBNP =2,400 pg/mL for subjects presenting with atrial fibrillation when the blood sample was taken
iii. For subjects treated with an angiotensin receptor neprilysin inhibitor (ARNI) in the previous 4 weeks prior to randomisation only NT-proBNP values should be considered
d AHF episode treated with minimally 40 mg of IV furosemide (or equivalent IV loop diuretic defined as 20 mg of torsemide or 1 mg of bumetanide)
2. Subject is iron deficient defined as serum ferritin <100 ng/mL or 100 ng/mL = serum ferritin =299 ng/mL if TSAT <20%.
3. Left ventricular ejection fraction <50% (assessed and documented within 12 months prior to randomisation).
4. Male or female aged =18 years old.
5. Subject (or legally acceptable representative)* has provided the appropriate written informed consent. Subject must provide written informed consent before any study-specific procedures are performed.
*Following section in Italics are applicable for the Netherlands only (NL
only): The option that legally accepted representatives of subjects can
sign the written informed consent is not valid for sites in the
Netherlands
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600
1. Dyspnoea due to non-cardiac causes such as acute or chronic respiratory disorders or infections (i.e., severe chronic obstructive pulmonary disease, acute bronchitis, pneumonia, primary pulmonary hypertension).
2. Temperature >38°C (oral or equivalent), active infective endocarditis, sepsis, systemic inflammatory response syndrome, or any other active infection requiring anti-microbial treatment at any time during an Index hospitalisation.
3. Clinical evidence of acute coronary syndrome, transient ischemic attack or stroke, within the last 30 days prior randomisation.
4. Coronary-artery bypass graft, cardiac resynchronisation therapy device implantation, percutaneous intervention (e.g., cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery that led to significant blood loss, including thoracic and cardiac surgery, within the last 3 months prior to randomisation.
5. Subject has a body weight <35 kg at randomisation.
6. Subject at an immediate need of transfusion or with a Hb <8 g/dL* or with a Hb >15 g/dL.
7. Subject with a known anaemia not attributed to ID (e.g., other microcytic anaemia) or with an evidence of iron overload (e.g., haemochromatosis) or disturbances in the utilisation of iron.
8. Subject has known hypersensitivity to any of the study products to be administered or known serious hypersensitivity to other parenteral iron products.
9. Renal dialysis (previous, current or planned within the next 6 months).
10. Chronic liver disease (including active hepatitis) and/or alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range.
11. Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.
12. Subject is pregnant (e.g., positive human chorionic gonadotropin test) or breast feeding.
*Following section in Italics are applicable for the Netherlands only (NL
only): The lower threshold of Hb values is set to 10 g/dL.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate, relative to placebo, the effect of intravenous (IV) FCM on repeated heart failure (HF) hospitalisations and cardiovascular (CV) death.;Secondary Objective: To evaluate, relative to placebo, the effect of IV FCM on: HF hospitalizations, CV hospitalizations, CV mortality and all cause mortality Quality of life and New York Heart Association Classification (NYHA) Tolerability and safety.;Primary end point(s): The composite of recurrent HF hospitalizations and CV death up to 52 weeks after randomization.;Timepoint(s) of evaluation of this end point: Up to 52 weeks after randomization.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Safety Endpoints :<br>• Summary of adverse events (AEs): by system organ class and preferred term (Medical Dictionary for Regulatory Activities (MedDRA) coded term), by severity and relation to study product.<br>• Summary of serious adverse events (SAEs) by study treatment group presented by system organ class and preferred terms (MedDRA coded term).<br>• Summary of clinical laboratory panels and cardiac biomarkers (absolute and change from baseline).<br>;Timepoint(s) of evaluation of this end point: Up to 52 weeks after randomization