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

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ClinicalTrials.gov Identifier: NCT02937454
Recruitment Status : Recruiting
First Posted : October 18, 2016
Last Update Posted : February 25, 2019
Sponsor:
Collaborators:
Worldwide Clinical Trials
Cytel Inc.
Information provided by (Responsible Party):
Vifor Inc.

Tracking Information
First Submitted Date  ICMJE October 14, 2016
First Posted Date  ICMJE October 18, 2016
Last Update Posted Date February 25, 2019
Actual Study Start Date  ICMJE April 3, 2017
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
HF hospitalizations and CV death up to 52 weeks after randomization [ Time Frame: up to 52 weeks after randomization ]
The composite of recurrent HF hospitalizations and CV death up to 52 weeks after randomization
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02937454 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2019)
  • Recurrent CV hospitalisations and CV death 52 weeks after randomisation. [ Time Frame: up to 52 weeks after randomization ]
    The composite of recurrent CV hospitalisations and CV death at 52 weeks after randomisation
  • HF hospitalisations up to 52 weeks after randomisation [ Time Frame: up to 52 weeks after randomisation ]
    HF hospitalisations up to 52 weeks after randomisation analysed as recurrent event.
  • CV mortality [ Time Frame: at 52 weeks after randomisation. ]
    CV mortality analysed as time to first event at 52 weeks after randomisation.
  • The composite of HF hospitalisations or CV death [ Time Frame: at 52 weeks after randomisation ]
    Analysed as time to first event at 52 weeks after randomisation
  • Days lost due to HF hospitalisation or CV death at 52 weeks [ Time Frame: at 52 weeks after randomisation ]
    Days lost due to HF hospitalisation or CV death at 52 weeks after randomisation
Original Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
  • HF hospitalisations or cardiovascular (CV) death analysed as time to first event . [ Time Frame: at 52 weeks after randomisation ]
    The composite of HF hospitalisations or CV death analysed as time to first event 52 weeks after randomisation.
  • Recurrent CV hospitalisations and CV death 52 weeks after randomisation. [ Time Frame: at 52 weeks after randomization ]
    The composite of recurrent CV hospitalisations and CV death at 52 weeks after randomisation
  • CV hospitalisations or CV death analysed as time to first event [ Time Frame: at 52 weeks after randomisation ]
    Composite of CV hospitalisations or CV death analysed as time to first event at 52 weeks after randomisation.
  • CV mortality [ Time Frame: at 52 weeks after randomisation. ]
    CV mortality analysed as time to first event at 52 weeks after randomisation.
  • All-cause mortality [ Time Frame: at 52 weeks after randomisation ]
    All-cause mortality analysed as time to first event at 52 weeks after randomisation.
  • New York Heart Association (NYHA) functional class [ Time Frame: up to 52 weeks after randomisation. ]
    Change from baseline in NYHA functional class as assessed up to 52 weeks after randomisation.
  • Change from baseline in the Kansas City Cardiomyopathy Questionnaire-12 [ Time Frame: up to 52 weeks after randomisation. ]
    Change from baseline in the Kansas City Cardiomyopathy Questionnaire-12 up to 52 weeks after randomisation.
  • Change from baseline in the European quality of life - 5 dimensions questionnaire [ Time Frame: up to 52 weeks after randomisation ]
    Change from baseline in the European quality of life - 5 dimensions questionnaire up to 52 weeks after randomisation.
Current Other Outcome Measures  ICMJE
 (submitted: February 21, 2019)
  • Recurrent HF hospitalisations and CV death up to 30 days after randomisation [ Time Frame: up to 30 days after randomisation ]
    The composite of recurrent HF hospitalisations and CV death up to 30 days after randomisation
  • Recurrent CV hospitalisations and CV death up to 30 days after randomisation. [ Time Frame: up to 30 days after randomisation ]
    The composite of recurrent CV hospitalisations and CV death up to 30 days after randomisation
  • HF hospitalisations or CV death at 30 days after randomisation. [ Time Frame: at 30 days after randomisation ]
    The composite of HF hospitalisations or CV death analysed as time to first event at 30 days after randomisation.
  • CV hospitalisations or CV death up to 30 days after randomisation [ Time Frame: up to 30 days after randomisation ]
    The composite of CV hospitalisations or CV death analysed as recurrent event at 30 days after randomisation.
  • HF hospitalisations up to 30 days and 52 weeks after randomisation [ Time Frame: up to 30 days and 52 weeks after randomisation ]
    HF hospitalisations up to 30 days and 52 weeks after randomisation analysed as time to first event
  • HF hospitalisations up to 30 days after randomisation [ Time Frame: up to 30 days after randomisation ]
    HF hospitalisations up to 30 days after randomisation (analyzed as a recurrent event)
  • CV hospitalisations up to 30 days and 52 weeks after randomisation [ Time Frame: up to 30 days and 52 weeks after randomisation ]
    CV hospitalisations up to 30 days and 52 weeks after randomisation (analysed as recurrent event and time to first event).
  • CV hospitalisations or CV death at 30 days and 52 weeks after randomisation. [ Time Frame: at 30 days and 52 weeks after randomisation ]
    The composite of CV hospitalisations or CV death analysed as time to first event at 30 days and 52 weeks after randomisation.
  • CV mortality at 30 days after randomisation [ Time Frame: at 30 days after randomisation ]
    CV mortality at 30 days after randomisation analysed as time to first event
  • All-cause mortality at 30 days and 52 weeks after randomisation [ Time Frame: at 30 days and 52 weeks after randomisation ]
    All-cause mortality at 30 days and 52 weeks after randomisation analysed as time to first event
  • Proportion of patients with an event [ Time Frame: up to 52 weeks ]
    Proportion of patients with an event (HF hospitalisations, CV hospitalisations, CV mortality; composite and individual categories).
  • Change from baseline in NYHA functional class [ Time Frame: at 6, 12, 24 and 52 weeks after randomisation. ]
    Change from baseline in NYHA functional class as assessed at 6, 12, 24 and 52 weeks after randomisation.
  • Change from baseline in the Kansas City Cardiomyopathy Questionnaire-12 [ Time Frame: up to 52 weeks after randomisation. ]
    Change from baseline in the Kansas City Cardiomyopathy Questionnaire-12 up to 52 weeks after randomisation.
  • Change from baseline in the European quality of life - 5 dimensions questionnaire [ Time Frame: up to 52 weeks after randomisation ]
    Change from baseline in the European quality of life - 5 dimensions questionnaire up to 52 weeks after randomisation.
  • Days lost due to HF hospitalisations or CV death [ Time Frame: at 30 days after randomisation ]
    Days lost due to HF hospitalisations or CV death at 30 days after randomisation
Original Other Outcome Measures  ICMJE
 (submitted: October 14, 2016)
  • Summary of adverse events [ Time Frame: up to 52 weeks after randomisation ]
    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.
  • Summary of serious adverse events (SAEs) by study treatment group [ Time Frame: up to 52 weeks after randomisation ]
    Summary of serious adverse events (SAEs) by study treatment group presented by system organ class and preferred terms (MedDRA coded term).
  • Summary of clinical laboratory panels [ Time Frame: up to 52 weeks after randomisation ]
    Summary of clinical laboratory panels (absolute and change from baseline).
 
Descriptive Information
Brief Title  ICMJE Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency
Official Title  ICMJE 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)
Brief Summary Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (Affirm-AHF)
Detailed Description This is a randomised, double-blind, placebo-controlled Trial (RCT). The 52 weeks observation period following randomisation is considered appropriate to investigate the primary endpoint of recurrent HF hospitalisations and CV death. To evaluate the effect of intravenous ferric carboxymaltose (IV FCM) in iron deficient subjects with AHF, subjects will be enrolled during a hospital stay (Index hospitalisation) after the acute care treatment of the index event has been stabilised. All subjects will continue to receive their established standard therapy for HF and medical emergencies will be treated according to local routine.
Study Type  ICMJE Interventional
Study Phase Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Iron Deficiency
  • Heart Failure
Intervention  ICMJE
  • 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:
    • Injectafer
    • Ferinject
    • Renegy
    • Iroprem
  • Other: Normal saline 0.9%
    Normal saline will be administered as a bolus injection.
Study Arms
  • 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.
    Intervention: Drug: ferric carboxymaltose
  • 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.
    Intervention: Other: Normal saline 0.9%
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 14, 2016)
1100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date August 2020
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Udo-Michael Gohring, MD +41 58 851 81 26 udo-michael.goehring@viforpharma.com
Listed Location Countries  ICMJE Argentina,   Brazil,   Croatia,   Georgia,   Israel,   Italy,   Lebanon,   Netherlands,   Poland,   Romania,   Singapore,   Spain,   Sweden,   Ukraine,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02937454
Other Study ID Numbers  ICMJE FER-CARS-06
2016-001467-36 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Vifor Inc.
Study Sponsor  ICMJE Vifor Inc.
Collaborators  ICMJE
  • Worldwide Clinical Trials
  • Cytel Inc.
Investigators  ICMJE
Principal Investigator: Piotr Ponikowski, MD Medical University Clinical Military Hospital
PRS Account Vifor Inc.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP