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 Hospitalization for Heart Failure (COMMANDER HF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01877915
First received: June 12, 2013
Last updated: April 24, 2014
Last verified: April 2014
  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 chronic heart failure and significant coronary artery disease following a recent hospitalization for exacerbation (worsening) of 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 Oral Rivaroxaban With Placebo for Reducing the Risk of Death, Myocardial Infarction or Stroke in Subjects With Chronic Heart Failure and Significant Coronary Artery Disease Following a Hospitalization for Exacerbation of 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 ]
  • Time to 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: February 2016
Estimated Primary Completion Date: February 2016 (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 chronic heart failure and significant coronary artery disease following hospitalization for exacerbation of 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 documented symptomatic chronic heart failure for at least 3 months prior to screening and must hospitalized for exacerbation of chronic heart failure (index hospitalization) before randomization
  • Must have a documented left ventricular ejection fraction of less than or equal to 40% within 3 months 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 be receiving appropriate treatment for heart failure or coronary artery disease at the appropriate dosing per guidelines

Exclusion Criteria:

  • Any condition that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an unacceptable risk of bleeding
  • Severe concomitant disease or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments
  • Prior stroke within 90 days of randomization
  • Has been hospitalized for longer than 21 days during the index hospitalization
  • 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 341 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
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: April 24, 2014
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
Ukraine: State Pharmacological Center - Ministry of Health
Germany: Ethics Commission
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines

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

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Failure
Infarction
Myocardial Infarction
Stroke
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ischemia
Pathologic Processes
Necrosis
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on July 28, 2014