Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (Affirm-AHF)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02937454 |
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Recruitment Status :
Completed
First Posted : October 18, 2016
Results First Posted : June 18, 2021
Last Update Posted : June 18, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Iron Deficiency Heart Failure | Drug: ferric carboxymaltose Other: Normal saline 0.9% | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1132 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official 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) |
| Actual Study Start Date : | April 3, 2017 |
| Actual Primary Completion Date : | July 21, 2020 |
| Actual Study Completion Date : | July 21, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: ferric carboxymaltose
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.
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Drug: ferric carboxymaltose
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
Other Names:
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Placebo Comparator: normal saline 0.9%
The first dose of study treatment will be administered for all randomised subjects on the same day as randomisation.
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Other: Normal saline 0.9%
Normal saline will be administered as a bolus injection. |
- HF Hospitalizations and CV Death [ Time Frame: up to 52 weeks after randomization ]
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.
- Recurrent CV Hospitalisations and CV Death [ Time Frame: up to 52 weeks after randomization ]
CV = Cardiovascular
The composite of recurrent CV hospitalisations and CV death at 52 weeks after randomisation
Total hospitalisations included first and recurrent events. If a participant was hospitalised for a cardiovascular reason and died within 24 h of admission from any cardiovascular event, this was counted as one event.
- HF Hospitalisations [ Time Frame: up to 52 weeks after randomisation ]
HF = Heart Failure
HF hospitalisations up to 52 weeks after randomisation analysed as recurrent event.
- CV Mortality [ Time Frame: at 52 weeks after randomisation. ]
CV = Cardiovascular
CV mortality analysed as time to first event at 52 weeks after randomisation.
- Composite of HF Hospitalisations or CV Death [ Time Frame: at 52 weeks after randomisation ]
HF = Heart Failure, CV = Cardiovascular
Analysed as time to first event at 52 weeks after randomisation. The number of participants with at least one HF Hospitalisation or CV Death is presented below.
- Days Lost Due to HF Hospitalisation or CV Death [ Time Frame: at 52 weeks after randomisation ]
HF = Heart Failure, CV = Cardiovascular
Number of days lost due to heart failure hospitalisations or cardiovascular death corresponds to the total number of days in hospital for heart failure from randomisation to last known date. Days lost due to cardiovascular death are added to the number of days lost due to heart failure hospitalisation.
- HF Hospitalisations [ Time Frame: up to 52 weeks after randomisation ]
HF = Heart Failure
Number of participants with at least one HF Hospitalisation up to 52 weeks after randomisation
- CV Hospitalisations [ Time Frame: up to 52 weeks after randomisation ]
CV = Cardiovascular
Number of participants with at least one CV Hospitalisation up to 52 weeks after randomisation
- All-cause Mortality [ Time Frame: up to 52 weeks after randomisation ]Number of participants who died up to 52 weeks after randomisation
- Change From Baseline in NYHA Functional Class [ Time Frame: at 6, 12, 24 and 52 weeks after randomisation ]
NYHA = New York Heart Association
NYHA functional class was assessed as Class I, II, III, IV or V:
Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.
Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest.
Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. If a participant was hospitalised at any point during any post-baseline visit and did not have any NYHA assessment for this visit, then Class IV was to be imputed for the visit.
Class V - Imputed for participants who died.
Lower response categories are better for score NYHA.
- Change From Baseline in the EQ-5D-5L Questionnaire Indexed Value [ Time Frame: at 6, 24 and 52 weeks after randomisation ]
EQ-5D-5L: European Quality of Life-5 Dimensions-5 Levels
The EQ 5D questionnaire consists of a health descriptive system for participants to self-classify and rate their health status on the day of administration.
The descriptive system includes 5 items/dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, which are coded from 1 (best state) to 5 (worst state).
- KCCQ-12 Repeated-Measures Model for Analysis of Treatment Difference [ Time Frame: up to 52 weeks after randomisation ]
KCCQ = Kansas City Cardiomyopathy Questionnaire
The KCCQ 12 is a health-related quality of life questionnaire for Heart Failure. It is a 12 item questionnaire that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge and Quality of life. Scores are generated for each domain and scaled from 0 to 100, with 0 denoting the lowest reportable health status and 100 the highest reportable health status.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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.
Exclusion Criteria:
- 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.
- Renal dialysis (previous, current or planned within the next 6 months).
- 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.
- Terminal illness other than HF with expected survival <12 months.
- Chronic liver disease (including active hepatitis) and/or alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range.
- Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.
- 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.
- 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).
- Subject is pregnant (e.g., positive human chorionic gonadotropin test) or breast feeding.
- 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.
- Subject has a history of drug or alcohol abuse within 2 years prior to screening.
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Subject has a significant medical condition(s), anticipated need for major surgery during the study, or any other kind of disorder that may be associated with increased risk to the subject, or may interfere with study assessments, outcomes, or the ability to provide written informed consent or comply with study procedures, in the Investigator's opinion.
- Following section in italics is applicable for The Netherlands, Spain and Singapore only (NL, ES and SG only): 'The lower threshold of Hb values is set to 10 g/dL.'
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02937454
| Argentina | |
| Hospital Universitario Austral | |
| Buenos Aires, Argentina, 1500 | |
| Brazil | |
| InCor -Instituto do Coração HCFMUSP | |
| São Paulo, Brazil, 05403-900 | |
| Croatia | |
| Clinical Hospital Center Rijeka | |
| Rijeka, Croatia | |
| Georgia | |
| Aleksandre Aladashvili Clinic LLC | |
| Tbilisi, Georgia, 0102 | |
| Israel | |
| The Baruch Pade Medical Center | |
| Tiberias, Lower Galilee, Israel, 15208 | |
| Hadassah Ein Kerem University Medical Center | |
| Jerusalem, Israel, 91120 | |
| Italy | |
| Spedali Civilia di Brescia | |
| Brescia, Italy | |
| Lebanon | |
| American University of Beirut Medical Center | |
| Beirut, Lebanon, 1107-2020 | |
| Netherlands | |
| Vasculair Onderzoek Centrum | |
| Hoorn, Netherlands | |
| Poland | |
| Clinical Military Hospital | |
| Wroclaw, Poland, 50-891 | |
| Romania | |
| Emergency Clinical Hospital | |
| Bucharest, Romania, 014461 | |
| Singapore | |
| National Heart Centre of Singapore Pte | |
| Singapore, Singapore, 169609 | |
| Spain | |
| University of Murcia | |
| Murcia, Spain, 30001 | |
| Sweden | |
| Skane University Hospital | |
| Malmö, Sweden, SE 20502 | |
| Ukraine | |
| The M.D. Strazhesko Institute of Cardiology | |
| Kyiv, Ukraine, 02000 | |
| United Kingdom | |
| Kings College Hospital NHS Foundation | |
| London, United Kingdom | |
| Principal Investigator: | Piotr Ponikowski, MD | Medical University Clinical Military Hospital |
Documents provided by Vifor Pharma ( Vifor (International) Inc. ):
| Responsible Party: | Vifor (International) Inc. |
| ClinicalTrials.gov Identifier: | NCT02937454 |
| Other Study ID Numbers: |
FER-CARS-06 2016-001467-36 ( EudraCT Number ) |
| First Posted: | October 18, 2016 Key Record Dates |
| Results First Posted: | June 18, 2021 |
| Last Update Posted: | June 18, 2021 |
| Last Verified: | May 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Acute Heart Failure Iron Deficiency |
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Heart Failure Anemia, Iron-Deficiency Iron Deficiencies Heart Diseases Cardiovascular Diseases |
Iron Metabolism Disorders Metabolic Diseases Anemia, Hypochromic Anemia Hematologic Diseases |