E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of death, heart attack and stroke in patients with heart failure and significant coronary artery disease following an episode of decompensated HF (index event). |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with heart failure following an index event. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
|
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 |
The primary objective is to demonstrate that rivaroxaban is superior to placebo in subjects with HF and significant CAD, who are receiving standard care, in reducing the risk of the composite of ACM, MI, or stroke following an index event. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare rivaroxaban with placebo in addition to standard care in subjects with HF and significant CAD following an index event in reducing the risk of the following outcomes:
•Composite of cardiovascular mortality and re-hospitalization for worsening heart failure
•Cardiovascular mortality
•Re-hospitalization for worsening of heart failure
•Re-hospitalization for cardiovascular events
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Must have symptomatic heart failure for at least 3 months prior to Screening
- Participants must have an episode of decompensated heart failure (index event) requiring:
a) an overnight stay [that is, staying past midnight] in a hospital, emergency department, or medical facility with the capability of treating with intravenous medications and observing heart failure patients before randomization or;
b) an unscheduled outpatient visit to a heart failure management center, where parenteral therapy is required for heart failure stabilization. An episode of decompensated heart failure is defined as symptoms of worsening dyspnea or fatigue, objective signs of congestion such as peripheral edema or ascites, and/or adjustment of pre-hospitalization/outpatient visit heart failure medications. Participants are eligible for randomization at discharge from the facility treating the index event and up to 30 days after discharge if they are in stable condition
- Must have a documented left ventricular ejection fraction (LVEF) of less than or equal to 40 percent (%) within 1 year before randomization
- Must have evidence of significant coronary artery disease
- Must be medically stable in terms of heart failure clinical status at the time of randomization
- Must have a brain natriuretic peptide (BNP) level greater than or equal to (>=) 200 picogram per milliliter (pg/ml) or N-terminal-proBNP (NT-proBNP) level >=800 pg/ml (preferred assay) during the Screening period and before randomization |
|
E.4 | Principal exclusion criteria |
- Any condition that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an unacceptable risk of bleeding, such as, but not limited to, active internal bleeding, clinically significant bleeding, bleeding at noncompressible site, or bleeding diathesis within 28 days of randomization
- Severe concomitant disease such as:
a) atrial fibrilation (AFib) or another condition that requires chronic anticoagulation (participants with isolated transient AFib may be allowed at the discretion of the treating physician investigator) and;
b) Documented acute myocardial infarction (MI) during index event
- Prior stroke within 90 days of randomization
- Has been hospitalized for longer than 21 days during the index event
- Planned intermittent outpatient treatment with positive inotropic drugs administered intravenously |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Time to the first occurence of any of the following: death from any cause, myocardial infarction, or stroke
- Time to the first occurence of either fatal bleeding or bleeding into a critical space with potential for permanent disability |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Day 1 up to approximately Month 30
- Day 1 up to approximately Month 30
|
|
E.5.2 | Secondary end point(s) |
- Time to the first occurence of either death due to a cardiovascular cause or re-hospitalization for worsening of heart failure
- Time to death due to a cardiovascular cause
- Time to rehospitalization for worsening of heart failure
- Time to rehospitalization for cardiovascular events
- Bleeding requiring hospitalization |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Day 1 up to approximately Month 30
- Day 1 up to approximately Month 30
- Day 1 up to approximately Month 30
- Day 1 up to approximately Month 30
- Day 1 up to approximately Month 30
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 142 |
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 | No |
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 |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
China |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
Poland |
Romania |
Russian Federation |
Spain |
Turkey |
Ukraine |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |