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.

Abstract

Aims: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF.

Methods: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes.

Conclusion: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.

Keywords: Acute heart failure; Cardiovascular mortality; Ferric carboxymaltose; Iron deficiency; Recurrent heart failure hospitalizations.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anemia, Iron-Deficiency / drug therapy*
  • Anemia, Iron-Deficiency / etiology
  • Anemia, Iron-Deficiency / mortality
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Ferric Compounds / administration & dosage*
  • Follow-Up Studies
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hospitalization / trends*
  • Humans
  • Injections, Intravenous
  • Inpatients*
  • Male
  • Maltose / administration & dosage
  • Maltose / analogs & derivatives*
  • Middle Aged
  • Quality of Life
  • Retrospective Studies
  • Survival Rate / trends
  • Switzerland / epidemiology
  • Treatment Outcome

Substances

  • Ferric Compounds
  • ferric carboxymaltose
  • Maltose

Associated data

  • ClinicalTrials.gov/NCT02937454