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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)

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ClinicalTrials.gov Identifier: NCT01877915
Recruitment Status : Completed
First Posted : June 14, 2013
Results First Posted : May 10, 2019
Last Update Posted : May 10, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE June 12, 2013
First Posted Date  ICMJE June 14, 2013
Results First Submitted Date  ICMJE April 18, 2019
Results First Posted Date  ICMJE May 10, 2019
Last Update Posted Date May 10, 2019
Actual Study Start Date  ICMJE September 10, 2013
Actual Primary Completion Date April 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • Event Rate of All-Cause Mortality, Myocardial Infarction (MI), or Stroke [ Time Frame: Up to Global treatment end date (approximately 54 months) ]
    Event Rate of all-cause mortality (ACM), MI, or stroke were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 patient [pt]-year [yr]) = 100*n/(total risk exposure), where n is the number of events.
  • Event Rate of Either Fatal Bleeding or Bleeding Into a Critical Space With Potential for Permanent Disability [ Time Frame: Up to 227 Weeks ]
    Event rate of either fatal bleeding or bleeding into critical space with potential for permanent disability were assessed. Fatal bleeding event was death within 7 days after a bleeding event which required hospitalization or met International Society on Thrombosis and Haemostasis(ISTH) major bleeding definition criteria. Fatal bleeding events included those met criteria in 3 categories: 1: Any ISTH major bleeding event consider primary cause of death by investigator; 2: Any ISTH major bleeding event not considered to be primary cause of death by investigator but resulted in death within 7 days;3: Any bleeding event resulted in hospital stay and death within 7 days. Bleeding into critical space with potential for permanent disability included 7 critical spaces: intracranial, intraspinal, intraocular. Event rate estimated based on time to first occurrence of event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Original Primary Outcome Measures  ICMJE
 (submitted: June 12, 2013)
  • 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 ]
  • 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 ]
Change History Complete list of historical versions of study NCT01877915 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • Event Rate of Cardio Vascular Death or Re-Hospitalization for Worsening of Heart Failure (RHHF) [ Time Frame: Up to Global treatment end date (approximately 54 months) ]
    Event rate of cardio vascular (CV) death or re-hospitalization for worsening of heart failure were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
  • Event Rate of Cardio Vascular Death [ Time Frame: Up to Global treatment end date (approximately 54 months) ]
    Event rate of cardio vascular death were assessed. CV death included deaths due to spontaneous bleeding, MI, stroke, worsening HF and arrhythmias, death due to CV procedures and sudden death. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
  • Event Rate of Re-Hospitalization for Worsening of Heart Failure [ Time Frame: Up to Global treatment end date (approximately 54 months) ]
    Event rate of re-hospitalization for worsening of heart failure were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
  • Event Rate of Re-Hospitalization for Cardio Vascular Events (RHCV) [ Time Frame: Up to Global treatment end date (approximately 54 months) ]
    Event rate due to cardio vascular events were assessed. Hospitalization for a CV Event required that participants be hospitalized (in-patient or emergency department) for greater than 24 hours and must have met the following criterion:Discharge summary with primary reason for admission listed as CV in nature (example, bleeding, arrhythmia, ACS, MI) other than HF which was captured in the HF re-hospitalization. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
  • Event Rate of All-Cause Mortality (ACM) or Re-Hospitalization for Worsening Heart Failure [ Time Frame: Up to Global treatment end date (approximately 54 months) ]
    Event rate of all-Cause Mortality (ACM) or re-Hospitalization for worsening heart failure were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
  • Event Rate of Bleeding Events That Requiring Hospitalization [ Time Frame: Up to 227 Weeks ]
    Event rate of bleeding events and required Hospitalization were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
  • Event Rate of International Society on Thrombosis and Haemostasis (ISTH) Major Bleeding Event [ Time Frame: Up to 227 Weeks ]
    Event rate of ISTH major bleeding event were assessed. Event rate estimated based on the time to the first occurrence of the event were reported in the study. Event Rate / (100 pt-yr) = 100*n/(total risk exposure), where n is the number of events.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2013)
  • 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 ]
  • Time to death due to a cardiovascular cause [ Time Frame: Day 1 up to approximately Month 30 ]
  • Time to rehospitalization for worsening of heart failure [ Time Frame: Day 1 up to approximately Month 30 ]
  • Time to rehospitalization for cardiovascular events [ Time Frame: Day 1 up to approximately Month 30 ]
  • Time to bleeding requiring hospitalization [ Time Frame: Day 1 up to approximately Month 30 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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.
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 1200 primary efficacy outcome events are predicted to have occurred). The double-blind treatment phase is estimated to last for 6 to 54 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 average study duration for participants is expected to be approximately 29 months. The study drug, rivaroxaban, is approved in the United States and in multiple countries around the world for the prevention and treatment of a number of thrombosis-mediated conditions.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Heart Failure
  • Coronary Artery Disease
Intervention  ICMJE
  • 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 1200 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).
  • 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.
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Rivaroxaban
    • Other: Standard of care for heart failure and coronary artery disease
  • 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).
    Interventions:
    • Drug: Placebo
    • Other: Standard of care for heart failure and coronary artery disease
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 7, 2018)
5081
Original Estimated Enrollment  ICMJE
 (submitted: June 12, 2013)
5000
Actual Study Completion Date  ICMJE April 19, 2018
Actual Primary Completion Date April 19, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 95 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Argentina,   Australia,   Brazil,   Bulgaria,   China,   Czechia,   Denmark,   Estonia,   France,   Germany,   Greece,   Hungary,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Netherlands,   Poland,   Portugal,   Romania,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01877915
Other Study ID Numbers  ICMJE CR101940
RIVAROXHFA3001 ( Other Identifier: Janssen Research & Development, LLC )
2013-000046-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Bayer
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP