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

• Register: ClinicalTrials.gov
• Last refreshed on: 11 January 2021
• Main ID: NCT02937454
• Date of registration: 14/10/2016
• Prospective Registration: Yes
• Primary sponsor: Vifor (International) Inc.
• Public title: Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency Affirm-AHF
• Scientific title: 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 (Affirm-AHF)
• Date of first enrolment: April 3, 2017
• Target sample size: 1132
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02937454
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Argentina, Brazil, Croatia, Georgia, Israel, Italy, Lebanon, Netherlands, Poland, Romania, Singapore, Spain, Sweden, Ukraine, United Kingdom

Contacts

• Name: Piotr Ponikowski, MD
• Affiliation: Medical University Clinical Military Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

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:

1. Upon admission for the AHF episode, persistent dyspnoea at rest in a recumbent
sitting position (30-45°) or with minimal exertion

2. 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)

3. 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

4. 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)

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.

Exclusion Criteria:

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. (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).

3. 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).

4. Clinical evidence of acute coronary syndrome, transient ischemic attack or stroke,
within the last 30 days prior randomisation.

5. Severe valvular or left ventricular outflow obstruction disease needing intervention.

6. 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.

7. Subject has a body weight <35 kg at randomisation.

8. Subject at an immediate need of transfusion or with a Hb <8 g/dL* or with a Hb >15
g/dL.

9. 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.

10. 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.

11. Subject has known hypersensitivity to any of the study products to be administered or
known serious hypersensitivity to other parenteral iron products.

12. 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).

13. History of erythropoietin stimulating agent, IV iron therapy, and/or blood transfusion
in previous 3 months prior to randomisation.

14. 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.

15. Currently receiving systemic chemotherapy and/or radiotherapy.

16. Renal dialysis (previous, current or planned within the next 6 months).

17. Subject has known active malignancy of any organ system, i.e., clinical evidence of
current malignancy or not in stable remission for at least 3 years since completion of
last treatment with exception of non-invasive basal cell carcinoma, squamous cell
carcinoma of the skin or cervical intra-epithelial neoplasia.

18. Terminal illness other than HF with expected survival <12 months.

19. Chronic liver disease (including active hepatitis) and/or alanine transaminase or
aspartate transaminase above 3 times the upper limit of the normal range.

20. Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus
ribonucleic acid positivity.

21. Subject previously randomised into this study. Note: Subjects may be rescreened but
when rescreened, all tests must fall inside the maximum specified screening windows
for each criterion.

22. Subject is currently enrolled in or has completed any other investigational device or
drug study <30 days prior to screening, or is receiving other investigational
agent(s).

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

24. If of childbearing potential, subject is not using adequate contraceptive precautions.
Subject must agree to use adequate contraception during the study and for 1 month
after the last dose of study treatment. A highly effective method of birth control
must be used.

25. Subject has a history of drug or alcohol abuse within 2 years prior to screening.

26. Subject has a significant medical condition(s), anticipated need for major


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Iron Deficiency

Heart Failure

Intervention(s)

Other: Normal saline 0.9%

Drug: ferric carboxymaltose

Primary Outcome(s)

HF hospitalizations and CV death up to 52 weeks after randomization [Time Frame: up to 52 weeks after randomization]

Secondary Outcome(s)

CV mortality [Time Frame: at 52 weeks after randomisation.]

The composite of HF hospitalisations or CV death [Time Frame: at 52 weeks after randomisation]

Days lost due to HF hospitalisation or CV death at 52 weeks [Time Frame: at 52 weeks after randomisation]

HF hospitalisations up to 52 weeks after randomisation [Time Frame: up to 52 weeks after randomisation]

Recurrent CV hospitalisations and CV death 52 weeks after randomisation. [Time Frame: up to 52 weeks after randomization]

Secondary ID(s)

FER-CARS-06

2016-001467-36

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Worldwide Clinical Trials

Cytel Inc.