Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency

NCT02937454 | Completed Phase 4 Results DMC

• 2 other identifiers: FER-CARS-062016-001467-36
• Study Type: interventional
• Target: 1,132
• Locations: 15 countries
• Sites: 16

Brief Summary

Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (Affirm-AHF)

Conditions

Iron Deficiency; Heart Failure

Keywords

Acute Heart Failure; Iron Deficiency

Outcome Measures

Primary Outcomes (1)

• HF Hospitalizations and CV Death

  HF = Heart Failure, CV = Cardiovascular. The composite of recurrent HF hospitalizations and CV death up to 52 weeks after randomization Total hospitalisations included first and recurrent events. If a participant was hospitalised for heart failure and died within 24 h from any cardiovascular event, this was counted as one event.

  up to 52 weeks after randomization

Secondary Outcomes (5)

• Recurrent CV Hospitalisations and CV Death

  up to 52 weeks after randomization

• HF Hospitalisations

  up to 52 weeks after randomisation

• CV Mortality

  at 52 weeks after randomisation.

• Composite of HF Hospitalisations or CV Death

  at 52 weeks after randomisation

• Days Lost Due to HF Hospitalisation or CV Death

  at 52 weeks after randomisation

Other Outcomes (6)

• HF Hospitalisations

  up to 52 weeks after randomisation

• CV Hospitalisations

  up to 52 weeks after randomisation

• All-cause Mortality

  up to 52 weeks after randomisation

Study Arms (2)

ferric carboxymaltose

ACTIVE COMPARATOR

The first dose of study treatment will be administered for all randomised subjects while the patient is still hospitalised for the Index hospitalisation. The subsequent administrations of study treatment will be done as part of the outpatient clinic visits.

Drug: ferric carboxymaltose

normal saline 0.9%

PLACEBO COMPARATOR

The first dose of study treatment will be administered for all randomised subjects on the same day as randomisation.

Other: Normal saline 0.9%

Interventions

ferric carboxymaltose DRUG

FCM will be administered as an undiluted bolus injection. The study treatment dose (mL) to be administered will be determined by the patient's body weight and haemoglobin (Hb) value at the respective visits where study treatment will be administered

Also known as: Injectafer, Ferinject, Renegy, Iroprem

ferric carboxymaltose

Normal saline 0.9% OTHER

Normal saline will be administered as a bolus injection.

normal saline 0.9%

Eligibility Criteria

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

You may qualify if:

• 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:
• Upon admission for the AHF episode, persistent dyspnoea at rest in a recumbent sitting position (30-45°) or with minimal exertion
• Upon or during the AHF admission, at least 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)
• Natriuretic peptide levels, measured ≤72 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
• AHF episode treated with minimally 40 mg of IV furosemide (or equivalent IV loop diuretic defined as 20 mg of torasemide or 1 mg of bumetanide)
• Subject is iron deficient defined as serum ferritin \<100 ng/mL or 100 ng/mL ≤ serum ferritin ≤299 ng/mL if TSAT \<20%.
• Left ventricular ejection fraction \<50% (assessed and documented within 12 months prior to randomisation).
• Male or female aged ≥18 years old.
• 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.

You may not qualify if:

• 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).
• 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. (Note that it does NOT include short-term prophylactic administration of antibiotics or short-term temperature elevation at admission which is no longer present at the time point of discharge/randomisation).
• Documented restricted amyloid myocardiopathy, or acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy. (Note that it does NOT include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).
• Clinical evidence of acute coronary syndrome, transient ischemic attack or stroke, within the last 30 days prior randomisation.
• Severe valvular or left ventricular outflow obstruction disease needing intervention.
• 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.
• Subject has a body weight \<35 kg at randomisation.
• Subject at an immediate need of transfusion or with a Hb \<8 g/dL\* or with a Hb \>15 g/dL.
• Subjects on treatment for Vitamin B12 and/or serum folate deficiency. Note: Use of Vitamin B12 and folic acid as supplement therapy (not for deficiency treatment) is permitted.
• 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.
• Subject has known hypersensitivity to any of the study products to be administered or known serious hypersensitivity to other parenteral iron products.
• Subject with known severe allergies including drug allergies, history of severe asthma, eczema or other atopic allergy and in subjects with immune or inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis).
• History of erythropoietin stimulating agent, IV iron therapy, and/or blood transfusion in previous 3 months prior to randomisation.
• Oral iron therapy at doses \>100 mg/day in previous 4 weeks prior to randomisation. Note: Ongoing use of multivitamins containing iron \<75 mg/day are permitted.
• Currently receiving systemic chemotherapy and/or radiotherapy.

Sponsors & Collaborators

• Vifor (International) Inc.: lead
• Worldwide Clinical Trials: collaborator
• Cytel Inc.: collaborator

Study Sites (16)

Hospital Universitario Austral

Buenos Aires, 1500, Argentina

Location

InCor -Instituto do Coração HCFMUSP

São Paulo, 05403-900, Brazil

Location

Clinical Hospital Center Rijeka

Rijeka, Croatia

Location

Aleksandre Aladashvili Clinic LLC

Tbilisi, 0102, Georgia

Location

The Baruch Pade Medical Center

Tiberias, Lower Galilee, 15208, Israel

Location

Hadassah Ein Kerem University Medical Center

Jerusalem, 91120, Israel

Location

Spedali Civilia di Brescia

Brescia, Italy

Location

American University of Beirut Medical Center

Beirut, 1107-2020, Lebanon

Location

Vasculair Onderzoek Centrum

Hoorn, Netherlands

Location

Clinical Military Hospital

Wroclaw, 50-891, Poland

Location

Emergency Clinical Hospital

Bucharest, 014461, Romania

Location

National Heart Centre of Singapore Pte

Singapore, 169609, Singapore

Location

University of Murcia

Murcia, 30001, Spain

Location

Skane University Hospital

Malmo, SE 20502, Sweden

Location

The M.D. Strazhesko Institute of Cardiology

Kyiv, 02000, Ukraine

Location

Kings College Hospital NHS Foundation

London, United Kingdom

Location

Related Publications (5)

• Rosano G, Ponikowski P, Vitale C, Anker SD, Butler J, Fabien V, Filippatos G, Kirwan BA, Macdougall IC, Metra M, Ruschitzka F, Kumpeson V, Goehring UM, van der Meer P, Jankowska EA; AFFIRM-AHF investigators. Intravenous ferric carboxymaltose for iron repletion following acute heart failure in patients with and without diabetes: a subgroup analysis of the randomized AFFIRM-AHF trial. Cardiovasc Diabetol. 2023 Aug 17;22(1):215. doi: 10.1186/s12933-023-01943-z.

  PMID: 37592272 DERIVED

• Macdougall IC, Ponikowski P, Stack AG, Wheeler DC, Anker SD, Butler J, Filippatos G, Gohring UM, Kirwan BA, Kumpeson V, Metra M, Rosano G, Ruschitzka F, van der Meer P, Wachter S, Jankowska EA. Ferric Carboxymaltose in Iron-Deficient Patients with Hospitalized Heart Failure and Reduced Kidney Function. Clin J Am Soc Nephrol. 2023 Sep 1;18(9):1124-1134. doi: 10.2215/CJN.0000000000000223. Epub 2023 Jun 29.

  PMID: 37382961 DERIVED

• Filippatos G, Ponikowski P, Farmakis D, Anker SD, Butler J, Fabien V, Kirwan BA, Macdougall IC, Metra M, Rosano G, Ruschitzka F, van der Meer P, Wachter S, Jankowska EA; AFFIRM-AHF Investigators. Association Between Hemoglobin Levels and Efficacy of Intravenous Ferric Carboxymaltose in Patients With Acute Heart Failure and Iron Deficiency: An AFFIRM-AHF Subgroup Analysis. Circulation. 2023 May 30;147(22):1640-1653. doi: 10.1161/CIRCULATIONAHA.122.060757. Epub 2023 Apr 13.

  PMID: 37051919 DERIVED

• Ponikowski P, Kirwan BA, Anker SD, McDonagh T, Dorobantu M, Drozdz J, Fabien V, Filippatos G, Gohring UM, Keren A, Khintibidze I, Kragten H, Martinez FA, Metra M, Milicic D, Nicolau JC, Ohlsson M, Parkhomenko A, Pascual-Figal DA, Ruschitzka F, Sim D, Skouri H, van der Meer P, Lewis BS, Comin-Colet J, von Haehling S, Cohen-Solal A, Danchin N, Doehner W, Dargie HJ, Motro M, Butler J, Friede T, Jensen KH, Pocock S, Jankowska EA; AFFIRM-AHF investigators. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 2020 Dec 12;396(10266):1895-1904. doi: 10.1016/S0140-6736(20)32339-4. Epub 2020 Nov 13.

  PMID: 33197395 DERIVED

• Ponikowski P, Kirwan BA, Anker SD, Dorobantu M, Drozdz J, Fabien V, Filippatos G, Haboubi T, Keren A, Khintibidze I, Kragten H, Martinez FA, McDonagh T, Metra M, Milicic D, Nicolau JC, Ohlsson M, Parhomenko A, Pascual-Figal DA, Ruschitzka F, Sim D, Skouri H, van der Meer P, Jankowska EA. Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure. Eur J Heart Fail. 2019 Dec;21(12):1651-1658. doi: 10.1002/ejhf.1710. Epub 2019 Dec 28.

  PMID: 31883356 DERIVED

MeSH Terms

Conditions

Iron Deficiencies; Heart Failure

Interventions

ferric carboxymaltose; Saline Solution

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: FER-CARS-06 Clinical Study Team
• Organization: Vifor (International) AG.

FER-CARS-06.study@viforpharma.com

+41 588 518 000

Study Officials

• Piotr Ponikowski, MD

  Medical University Clinical Military Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: October 18, 2016
• Study Start: April 3, 2017
• Primary Completion: July 21, 2020
• Study Completion: July 21, 2020
• Last Updated: June 18, 2021
• Results First Posted: June 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2); PL (1); AR (1); IT (1); GE (1); ES (1); GB (1); LE (1); UA (1); RO (1); SE (1); CR (1); BR (1); NL (1); SG (1)