A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER HF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Janssen Research & Development, LLC
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01877915
First received: June 12, 2013
Last updated: March 13, 2015
Last verified: March 2015
  Purpose

The purpose of this study is to assess the effectiveness and safety of rivaroxaban compared with placebo (inactive medication), in reducing the risk of death, myocardial infarction or stroke in participants with heart failure and significant coronary artery disease following an episode of decompensated heart failure.


Condition Intervention Phase
Heart Failure
Coronary Artery Disease
Drug: Rivaroxaban
Drug: Placebo
Other: Standard of care for heart failure and coronary artery disease
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Event-driven, Multicenter Study Comparing the Efficacy and Safety of Rivaroxaban With Placebo for Reducing the Risk of Death, Myocardial Infarction or Stroke in Subjects With Heart Failure and Significant Coronary Artery Disease Following an Episode of Decompensated Heart Failure

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Time to the first occurrence of any of the following: death from any cause, myocardial infarction, or stroke [ Time Frame: Day 1 up to approximately Month 30 ] [ Designated as safety issue: No ]
  • Time to the first occurrence of either fatal bleeding or bleeding into a critical space with potential for permanent disability [ Time Frame: Day 1 up to approximately Month 30 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to the first occurrence of either death due to a cardiovascular cause or re-hospitalization for worsening of heart failure [ Time Frame: Day 1 up to approximately Month 30 ] [ Designated as safety issue: No ]
    If both events occur (re-hospitalization and death) they will be separately counted as per outcome measures below.

  • Time to death due to a cardiovascular cause [ Time Frame: Day 1 up to approximately Month 30 ] [ Designated as safety issue: No ]
  • Time to rehospitalization for worsening of heart failure [ Time Frame: Day 1 up to approximately Month 30 ] [ Designated as safety issue: No ]
  • Time to rehospitalization for cardiovascular events [ Time Frame: Day 1 up to approximately Month 30 ] [ Designated as safety issue: No ]
  • Bleeding requiring hospitalization [ Time Frame: Day 1 up to approximately Month 30 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 5000
Study Start Date: September 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban 2.5 mg
Each participant will receive 2.5 mg of rivaroxaban twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Drug: Rivaroxaban
Each participant, randomly allocated to the rivaroxaban arm, will receive one 2.5 mg tablet of rivaroxaban orally (by mouth) twice daily (once in the morning and once in the evening at approximately the same time each day) until the global treatment end date (GTED) (defined as the date when 984 primary efficacy outcome events have occurred). Rivaroxaban will be given with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Other: Standard of care for heart failure and coronary artery disease
Each participant's standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician) should be continued throughout the study.
Placebo Comparator: Placebo
Each participant will receive matching placebo twice daily with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Drug: Placebo
Each participant, randomly allocated to the placebo arm, will receive one matching placebo tablet orally twice daily (once in the morning and once in the evening at approximately the same time each day) until the GTED. Placebo will be given with standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician).
Other: Standard of care for heart failure and coronary artery disease
Each participant's standard of care for heart failure and coronary artery disease (as prescribed by the participant's managing physician) should be continued throughout the study.

Detailed Description:

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), parallel group (each participant group receives different treatments simultaneously), event driven (the study duration is determined by the time taken for a specific number of events to occur), multicenter study to assess the effectiveness and safety of rivaroxaban compared with placebo, in reducing the risk of death, myocardial infarction or stroke in participants with heart failure and significant coronary artery disease following an episode of decompensated heart failure. Participants will be randomly assigned in a 1:1 ratio to receive either rivaroxaban or placebo (each in addition to standard of care for heart failure and coronary artery disease as prescribed by their managing physician). The study will consist of a screening phase, a double-blind treatment phase, and a follow-up after the sponsor-announced global treatment end date (GTED, defined as the date when 984 primary efficacy outcome events are predicted to have occurred). The double-blind treatment phase is estimated to last for 6 to 30 months. Participants will discontinue study drug after taking both their morning and evening doses on the GTED and will return to the study center for the end-of-study visit (between 15 and 45 days but no sooner than 15 days after the GTED). Patient safety will be monitored throughout the study. The study duration for each participant is expected to be approximately 16 months. The study drug, rivaroxaban, is approved in the United States and in several countries around the world for the prevention and treatment of a number of thrombosis-mediated conditions.

  Eligibility

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 their 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

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 a noncompressible site, or bleeding diathesis within 28 days of randomization
  • Severe concomitant disease such as (a) atrial fibrillation (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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01877915

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 504 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Bayer
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01877915     History of Changes
Other Study ID Numbers: CR101940, RIVAROXHFA3001, 2013-000046-19
Study First Received: June 12, 2013
Last Updated: March 13, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Bulgaria: Bulgarian Drug Agency
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Ukraine: Ministry of Health
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Japan: Pharmaceuticals and Medical Devices Agency
Canada: Health Canada
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Ukraine: State Pharmacological Center - Ministry of Health
Germany: Ethics Commission

Keywords provided by Janssen Research & Development, LLC:
Rivaroxaban
Heart Failure
Coronary Artery Disease
Stroke
Myocardial Infarction
Anticoagulation

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Heart Failure
Myocardial Infarction
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Vascular Diseases
Rivaroxaban
Anticoagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015