Primary Objective(s)* To evaluate, relative to placebo, the effect of intravenous (IV) FCM on repeated heart failure (HF) hospitalisations and cardiovascular (CV) death.Secondary Objective(s)* To evaluate, relative to placebo, the effect of IV FCM…
ID
Source
Brief title
Condition
- Other condition
- Heart failures
Synonym
Health condition
Iron Deficiency
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint
* The composite of recurrent HF hospitalisations and CV death up to 52 weeks
after randomisation
Secondary outcome
The secondary endpoints will evaluate, relative to placebo, the effect of IV
FCM on:
* The composite of recurrent CV hospitalisations and CV death up to 52 weeks
after randomisation.
* HF hospitalisations up to 52 weeks after randomisation (analysed as recurrent
event).
* CV mortality analysed as time to first event at 52 weeks after randomisation.
* The composite of HF hospitalisations or CV death analysed as time to first
event at 52 weeks after randomisation.
* Days lost due to HF hospitalisations or CV death at 52 weeks after
randomization.
Other Endpoints
The other endpoints will evaluate, relative to placebo, the effect of IV FCM on:
* The composite of recurrent HF hospitalisations and CV death up to 30 days
after randomisation.
* The composite of recurrent CV hospitalisations and CV death up to 30 days
after randomisation.
* The composite of HF hospitalisations or CV death analysed as time to first
event at 30 days after randomisation.
* The composite of CV hospitalisations or CV death analysed as time to first
event at 30 days after randomisation.
* HF hospitalisations up to 30 days after randomisation (analysed as recurrent
event).
* HF hospitalisations up to 30 days and 52 weeks after randomisation (analysed
as time to first event).
* CV hospitalisations up to 30 days and 52 weeks after randomisation (analysed
as recurrent event and time to first event).
* The composite of CV hospitalisations or CV death analysed as time to first
event at 30 days and 52 weeks after randomisation
* CV mortality analysed as time to first event at 30 days after randomisation.
* All-cause mortality analysed as time to first event at 30 days and 52 weeks
after randomisation.
* Proportion of patients with an event (HF hospitalisations, CV
hospitalisations, CV mortality; composite and individual categories).
* 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 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 at 30 days after
randomization.
Safety Endpoints:
* 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 presented
by system organ class and preferred terms (MedDRA coded term).
* Summary of clinical laboratory panels and cardiac biomarkers (absolute and
change from baseline).
Background summary
Acute heart failure (AHF) constitutes a clinically and economically challenging
problem. The prognosis of these patients remains poor, and so far, major
clinical trials have failed to improve outcomes in these patients. The current
treatment of AHF remained virtually unchanged in recent decades. iron
deficiency (ID) is frequent among patients with HF and predicts poor outcome.
Although, there are premises that correction of ID in AHF patients could
improve clinical outcomes, it has not been investigated to date.
Sponsor aims to investigate the effect of intravenous Ferric carboxymaltose (IV
FCM), relative to placebo on recurrent HF hospitalisations and CV death up to
52 weeks after randomisation in iron deficient subjects hospitalised for AHF.
Study objective
Primary Objective(s)
* To evaluate, relative to placebo, the effect of intravenous (IV) FCM on
repeated heart failure (HF) hospitalisations and cardiovascular (CV) death.
Secondary Objective(s)
* To evaluate, relative to placebo, the effect of IV FCM on:
* HF hospitalisations, CV hospitalisations, CV mortality and all-cause
mortality.
* Quality of life and New York Heart Association Classification (NYHA).
* Tolerability and safety.
Study design
Multicentre, randomised, double-blind prospective, parallel-group,
placebo-controlled, trial with a fixed follow-up of 52 weeks per patient after
randomization.
Eligible subjects will be randomised (1:1) to either FCM or placebo using a
validated centralised procedure (Interactive Voice response System (IVRS) or
Interactive Web-based Randomisation System (IWRS)).
* Active treatment arm: IV FCM
* Control treatment arm: IV NaCl 0.9%
Intervention
- dosing of drug
- venipuncture
- 12-lead Electrocardiogram
- Quality of Life questionnaires
Study burden and risks
In this clinical study the investigational product is ferric carboxymaltose.
Ferric carboxymaltose has been on the market since 2007 and over 7,300 patients
have already received this medication in clinical studies. There are known side
effects that have been seen in patients receiving ferric carboxymaltose. The
side effects may be temporary or have permanent consequences.
Known side effects which may occur during ferric carboxymaltose administration
or after having received ferric carboxymaltose include:
- Common side effects (may affect up to 1 in 10 people): headache, dizziness,
high blood pressure, nausea, feeling hot (flushing), and reactions around the
site of injection such as irritation, pain, bruising or potentially
long-lasting brownish discolouration following the leakage of the injection
into the skin.
- Uncommon side effects (may affect up to 1 in 100 people): allergic reactions,
numbness, tingling or prickling sensation on the skin, a change in your taste
sensation, high heart rate, low blood pressure, difficulty breathing, vomiting,
indigestion, stomach pain, constipation, diarrhoea, itching, hives, redness of
the skin, rash, muscle-, joint -and/or back pain, pain in extremities, muscle
spasms, fever, tiredness, chest pain, swelling of the hands and/or the feet,
and chills.
- Rare side effects (may affect up to 1 in 1,000 people): severe allergic
reactions (symptoms like rash, hives, itching, difficulty breathing, wheezing
and/or swelling of the lips, tongue, throat or body), general feeling of
discomfort, loss of consciousness, anxiety, fainting, feeling faint, paleness,
swelling of the face, and flu-like symptoms like fever, headache and/or feeling
ill.
Changes in blood values may occur. The following changes have been reported in
clinical trials as side effects:
* Common: decrease in blood phosphorus
* Uncommon: increase in certain liver enzymes called aspartate
aminotransferase, gamma-glutamyltransferase, alanine aminotransferase and
alkaline phosphatase, and increase in an enzyme called lactate dehydrogenase
Iron medication given directly into a vein can cause severe allergic reactions,
which may be potentially fatal. You will therefore be asked to remain in the
clinic for observation for 30 minutes after the end of your intravenous
injection
Electrocardiogram (ECG)
You can experience skin irritation from the Electrocardiogram (ECG) electrode
pads or brief itching when removing then.
Blood drawing procedure
Blood samples will be drawn from a vein in your arm at the scheduled visits by
a healthcare professional. Some known risks, although rare, can be associated
with the blood drawing procedure: pain at the injection site, bleeding, a
burning sensation, dizziness, fainting, a bruise or an infection at the site
where the needle was inserted to take the blood could occur. The maximum total
amount of blood to be drawn for study purposes is 50 mL/ approx. 10 teaspoons
for 5 samples
Rechenstrasse 37
St. Gallen CH-9001
CH
Rechenstrasse 37
St. Gallen CH-9001
CH
Listed location countries
Age
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:;a. Upon admission for the AHF episode, persistent dyspnoea at rest in a recumbent sitting position (30-45°) or with minimal exertion;b. Upon or during the AHF admission, at least two (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);c Natriuretic peptide levels, measured *24 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;d AHF episode treated with minimally 40 mg of IV furosemide (or equivalent IV loop diuretic defined as 20 mg of torsemide 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.
*Following section in Italics are applicable for the Netherlands only (NL
only): The option that legally accepted representatives of subjects can
sign the written informed consent is not valid for sites in the
Netherlands
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.;3. Clinical evidence of acute coronary syndrome, transient ischemic attack or stroke, within the last 30 days prior randomisation.;4. 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.;5. Subject has a body weight <35 kg at randomisation.;6. Subject at an immediate need of transfusion or with a Hb <8 g/dL* or with a Hb >15 g/dL.;7. 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.;8. Subject has known hypersensitivity to any of the study products to be administered or known serious hypersensitivity to other parenteral iron products.;9. Renal dialysis (previous, current or planned within the next 6 months).;10. Chronic liver disease (including active hepatitis) and/or alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range.;11. Subjects with known hepatitis B surface antigen positivity and/or hepatitis C virus ribonucleic acid positivity.;12. Subject is pregnant (e.g., positive human chorionic gonadotropin
test) or breast feeding.;*Following section in Italics are applicable for the Netherlands only (NL only): The lower threshold of Hb values is set to 10 g/dL.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-001467-36-NL |
| ClinicalTrials.gov | NCT02937454 |
| CCMO | NL59598.100.16 |