E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart Failure Subjects with Symptomatic Left Ventricular Systolic Dysfunction and Anemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007559 |
E.1.2 | Term | Cardiac failure congestive |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of darbepoetin alfa compared with placebo on the composite of time to death from any cause or first hospital admission for worsening HF in subjects with symptomatic left ventricular systolic dysfunction and anemia. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of treatment with darbepoetin alfa on • Time to death from any cause. • Time to cardiovascular death or first hospital admission for worsening HF, whichever occurs first. • Change from baseline to month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score. • Change from baseline to month 6 in KCCQ Symptom Frequency Score. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Before any study-specific procedure, the appropriate written informed consent must be obtained.
≥ 18 years of age at the time of randomization.
Heart failure ≥ 3 months, and of NYHA class II, III, and IV at the time of randomisation.
Left ventricular ejection fraction ≤ 40% by echocardiogram, radionuclide ventriculography, cardiac magnetic resonance imaging, or X-ray contrast ventriculography within 6 months prior to randomization. For patients with CRT, LVEF assessment for eligibility must be performed at least 3 months after device implantation.
Hemoglobin concentration must be ≥ 9.0 g/dL and ≤ 12.0 g/dL (average of 2 hemoglobin concentrations as measured by blinded [coded] HemoCue® analyzer).
Treated for HF with stable, optimal pharmacological therapy. In general, optimal treatment will include a beta-blocker and an ACE inhibitor and/or an ARB at doses shown to be efficacious in HF trials, unless not tolerated. Stable medical therapy is defined as having no new HF drug class introduced 4 weeks prior to randomization, although doses of all drugs being received may be adjusted throughout the trial.
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E.4 | Principal exclusion criteria |
Poorly controlled hypertension, defined as blood pressure > 160/100 mm Hg assessed on two separate occasions prior to randomization.
Serum creatinine > 3.0 mg/dL (> 265 μmol/L)
Heart failure primarily due to valvular heart disease or clinically significant valvular heart disease that might lead to surgical correction within 12 months of randomization.
Implantable cardioverter defibrillator (ICD) within 30 days prior to randomization or initiation of cardiac resynchronization therapy (CRT with/without ICD) within 3 months prior to randomization.
Routinely scheduled IV infusions for HF (eg, inotropes, vasodilators [eg, nesiritide], diuretics).
Acute myocardial infarction or cerebrovascular accident within 3 months prior to randomization.
Percutaneous intervention (cardiac, cerebrovascular, aortic) within 8 weeks prior to randomization. Major surgery, including thoracic or cardiac surgery, within 3 months prior to randomization.
Symptomatic tachyarrhythmia with an uncontrolled ventricular response (> 100 bpm at rest) or an untreated symptomatic bradyarrhythmia within 1 month prior to randomization.
Hypertrophic obstructive cardiomyopathy, active myocarditis, or constrictive pericarditis.
Likely to receive cardiac transplant within 12 months after randomization.
Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow) or receiving renal replacement therapy.
Anemia that is due to acute or chronic bleeding.
Transferrin saturation (Tsat) < 15% at the time of screening (value rounded to the nearest full percentage point).
Serum vitamin B12 or folate level below the lower limit of normal.
Whole blood or red blood cell (RBC) transfusion within 8 weeks prior to randomization.
Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years.
Receiving or has received chemotherapy and/or radiation therapy for treatment of a malignancy within 6 months prior to randomization or clinical evidence of current malignancy, with the following exceptions: localized basal or squamous cell carcinoma of the skin or cervical intraepithelial neoplasia.
Known active systemic hematologic disease (eg, sickle cell anemia, myelodysplastic syndromes, hematologic malignancy, myeloma, hemolytic anemia), hemolysis due to any cause, thalassemia.
Untreated hypothyroidism or hyperthyroidism, adrenal insufficiency, active vasculitis due to collagen vascular disease.
Use of any erythropoietic protein (eg, rHuEPO) within 12 weeks prior to randomization.
Known hypersensitivity to any of the products to be administered during the study, including oral or IV iron.
Subject is pregnant (eg, positive human chorionic gonadotropin [HCG] test), is breast feeding, or is of child-bearing potential and not using adequate contraceptive precautions.
Currently enrolled in, or at least 30 days not yet elapsed since ending participation in other investigational device or drug trial(s) or receiving other investigational agent(s) or procedure(s).
Subject has a disorder that compromises the ability of the subject to give written informed consent or to comply with study procedures.
Patients with existing cancer (with the following exceptions: localized basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia) are excluded from enrollment into the RED-HF Trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to death from any cause or first hospital admission for worsening HF, whichever is first.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 300 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study is an event-driven trial and will conclude when approximately 1150 events occur that meet criteria for the adjudicated primary endpoint.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |