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NCT01776424: COMPASS

Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease

Completed Phase 3 Results posted Last updated 28 November 2022
What this trial tests

Phase 3 trial testing Rivaroxaban (Xarelto, BAY59-7939) in Prevention & Control in 27,395 participants. Completed in 15 June 2021.

Timeline
28 February 2013
Primary endpoint
21 July 2017
15 June 2021

Quick facts

Lead sponsorBayer
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment27,395
Start date28 February 2013
Primary completion21 July 2017
Estimated completion15 June 2021
Sites565 locations across Italy, Colombia, Finland, Japan, Ecuador, Malaysia, Ireland, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with Prevention & Control. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

The First Occurrence of the Composite Primary Efficacy Outcome, Myocardial Infarction (MI), Stroke, or Cardiovascular (CV) Death Primary · For each participant, the first occurrence of the composite primary efficacy outcome after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.

Count of participants and time from randomization to the first occurrence of the composite primary efficacy outcome, MI, stroke, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis.

GroupValue95% CI
Rivaroxaban 2.5mg + Aspirin 100mg379
Rivaroxaban 5mg + Aspirin Placebo448
Rivaroxaban Placebo + Aspirin 100mg496
The First Occurrence of the Primary Safety Outcome Major Bleeding Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria Primary · For each participant, the first occurrence of modified ISTH major bleeding after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.

Modified ISTH major bleeding is defined as: i) Fatal bleeding, or ii) Symptomatic bleeding in a critical area or organ, such as intraarticular, intracranial, intramuscular with compartment syndrome, intraocular, intraspinal, liver, pancreas, pericardial, respiratory, retroperitoneal, adrenal gland or kidney; or bleeding into the surgical site requiring reoperation, or iii) Bleeding leading to hospitalization (major bleeding also includes presentation to an acute care facility with discharge on the same day). Count of participants and time from randomization to the first occurrence of the prim

GroupValue95% CI
Rivaroxaban 2.5mg + Aspirin 100mg288
Rivaroxaban 5mg + Aspirin Placebo255
Rivaroxaban Placebo + Aspirin 100mg170
The First Occurrence of Myocardial Infarction (MI), Ischemic Stroke, Acute Limb Ischemia (ALI), or Coronary Heart Disease (CHD) Death Secondary · For each participant, the first occurrence of MI, ALI, or CHD death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.

Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CHD death were evaluated. Hazard ratios were calculated and reported as statistical analysis.

GroupValue95% CI
Rivaroxaban 2.5mg + Aspirin 100mg329
Rivaroxaban 5mg + Aspirin Placebo397
Rivaroxaban Placebo + Aspirin 100mg450
The First Occurrence of MI, Ischemic Stroke, ALI, or Cardiovascular (CV) Death Secondary · For each participant, the first occurrence of MI, ischemic stroke, ALI, or CV death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.

Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis.

GroupValue95% CI
Rivaroxaban 2.5mg + Aspirin 100mg389
Rivaroxaban 5mg + Aspirin Placebo453
Rivaroxaban Placebo + Aspirin 100mg516
All-cause Mortality Secondary · For each participants, death by any cause after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.

Count of participants and time from randomization to death by all cause were evaluated. Hazard ratios were calculated and reported as statistical analysis.

GroupValue95% CI
Rivaroxaban 2.5mg + Aspirin 100mg313
Rivaroxaban 5mg + Aspirin Placebo366
Rivaroxaban Placebo + Aspirin 100mg378
The First Occurrence of the Composite Primary Efficacy Outcome, Myocardial Infarction (MI), Stroke, or Cardiovascular (CV) Death in LTOLE Part Secondary · For each participant, the first occurrence of the composite primary efficacy outcome after from COMPASS LTOLE initiation visit up until last LTOLE part contact date was considered. The mean time in follow-up was 428 days.

Count of participants from COMPASS LTOLE initiation visit to the first occurrence of the composite primary efficacy outcome, MI, stroke, or CV death were evaluated. LTOLE: long-term open-lable extension

GroupValue95% CI
LTOLE Part: Rivaroxaban 2.5mg + Aspirin 100mg353
The First Occurrence of the Primary Safety Outcome Major Bleeding Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria in LTOLE Part Secondary · For each participant, the first occurrence of modified ISTH major bleeding from COMPASS LTOLE initiation visit up until 2 days after the last treatment in LTOLE part was considered. The mean time in follow-up was 421 days.

Modified ISTH major bleeding is defined as: i) Fatal bleeding, or ii) Symptomatic bleeding in a critical area or organ, such as intraarticular, intracranial, intramuscular with compartment syndrome, intraocular, intraspinal, liver, pancreas, pericardial, respiratory, retroperitoneal, adrenal gland or kidney; or bleeding into the surgical site requiring reoperation, or iii) Bleeding leading to hospitalization (major bleeding also includes presentation to an acute care facility with discharge on the same day). Count of participants from COMPASS LTOLE initiation visit to the first occurrence of

GroupValue95% CI
LTOLE Part: Rivaroxaban 2.5mg + Aspirin 100mg138
All-cause Mortality in LTOLE Part Secondary · For each participants, death by any cause after COMPASS LTOLE initiation visit up until the the last LTOLE part contact date was considered. The mean time in follow-up until that date was 428 days.

Count of participants from COMPASS LTOLE initiation visit to death by all cause were evaluated. LTOLE: long-term open-lable extension

GroupValue95% CI
LTOLE Part: Rivaroxaban 2.5mg + Aspirin 100mg282

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) are reported: from randomization until 2 days after the last antithrombotic study treatment or until LTOLE part initiation visit (including a mean of 478 days in between) for randomized groups (2 years on average); OR from LTOLE initiation visit up until 2 days after the last treatment for LTOLE group (421 days on average). All-Cause Mortality encompasses all death cases until the last contact (2 years on average for randomized groups; 428 days on average for LTOLE group).. Reporting threshold: 0.1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rivaroxaban 2.5mg + Aspirin 100mg
Serious: 692/9134 (8%)
Deaths: 529/9152
Rivaroxaban 5mg + Aspirin Placebo
Serious: 664/9109 (7%)
Deaths: 566/9117
Rivaroxaban Placebo + Aspirin 100mg
Serious: 630/9107 (7%)
Deaths: 566/9126
LTOLE Rivaroxaban Rivaroxaban 2.5mg + Aspirin 100mg
Serious: 292/12903 (2%)
Deaths: 283/12964

Serious adverse events (846 terms)

ReactionSystemRivaroxaban 2.5mg + Aspiri…Rivaroxaban 5mg + Aspirin …Rivaroxaban Placebo + Aspi…LTOLE Rivaroxaban Rivaroxa…
Acute kidney injuryRenal and urinary disorders
PneumoniaInfections and infestations
SepsisInfections and infestations
CataractEye disorders
Urinary tract infectionInfections and infestations
Lung neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Large intestine polypGastrointestinal disorders
Chest painGeneral disorders
AnaemiaBlood and lymphatic system disorders
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
CholecystitisHepatobiliary disorders
AngiocardiogramInvestigations
CellulitisInfections and infestations
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
Pancreatitis acuteGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PancreatitisGastrointestinal disorders
Cholecystitis acuteHepatobiliary disorders
UrosepsisInfections and infestations
Wound infectionInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders
Gastric cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal failureRenal and urinary disorders
Other adverse events (58 terms — click to expand)

ReactionSystemRivaroxaban 2.5mg + Aspiri…Rivaroxaban 5mg + Aspirin …Rivaroxaban Placebo + Aspi…LTOLE Rivaroxaban Rivaroxa…
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
Haemorrhage subcutaneousSkin and subcutaneous tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
ContusionInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Abdominal pain upperGastrointestinal disorders
Diabetes mellitusMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
HypertensionVascular disorders
Atrial fibrillationCardiac disorders
InfluenzaInfections and infestations
HaematuriaRenal and urinary disorders
PruritusSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
EczemaSkin and subcutaneous tissue disorders
GastritisGastrointestinal disorders
Herpes zosterInfections and infestations
RashSkin and subcutaneous tissue disorders
Abdominal discomfortGastrointestinal disorders
Large intestine polypGastrointestinal disorders
GastroenteritisInfections and infestations
VertigoEar and labyrinth disorders
CataractEye disorders
Dental cariesGastrointestinal disorders
DyspepsiaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
BronchitisInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
StomatitisGastrointestinal disorders
Oedema peripheralGeneral disorders
PeriodontitisInfections and infestations
Occult blood positiveInvestigations
HypoaesthesiaNervous system disorders

Most-reported serious reactions: Acute kidney injury, Pneumonia, Sepsis, Cataract, Urinary tract infection, Lung neoplasm malignant, Large intestine polyp, Chest pain.

Data from ClinicalTrials.gov NCT01776424 adverse events section.

Sponsor's own description

The primary objectives of this study are: * To determine whether rivaroxaban 2.5 mg twice daily (bid) + aspirin 100 mg once daily (od) compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke, or cardiovascular death in subjects with coronary artery disease (CAD) or peripheral artery disease (PAD); * To determine whether rivaroxaban 5 mg bid compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke or cardiovascular death in subjects with CAD or PAD.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.
    Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, et al · · 2017 · cited 1562× · PMID 28844192 · DOI 10.1056/nejmoa1709118
  2. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial.
    Anand SS, Bosch J, Eikelboom JW, Connolly SJ, et al · · 2018 · cited 569× · PMID 29132880 · DOI 10.1016/s0140-6736(17)32409-1
  3. Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.
    Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, et al · · 2019 · cited 323× · PMID 31152740 · DOI 10.1053/j.gastro.2019.05.056
  4. Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial.
    Anand SS, Caron F, Eikelboom JW, Bosch J, et al · · 2018 · cited 284× · PMID 29540326 · DOI 10.1016/j.jacc.2018.03.008
  5. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.
    Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, et al · · 2018 · cited 229× · PMID 29132879 · DOI 10.1016/s0140-6736(17)32458-3
  6. Multifunctional nanoparticle-mediated combining therapy for human diseases.
    Li X, Peng X, Zoulikha M, Boafo GF, et al · · 2024 · cited 207× · PMID 38161204 · DOI 10.1038/s41392-023-01668-1
  7. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials.
    Scally B, Emberson JR, Spata E, Reith C, et al · · 2018 · cited 161× · PMID 29475806 · DOI 10.1016/s2468-1253(18)30037-2
  8. The COMPASS Trial: Net Clinical Benefit of Low-Dose Rivaroxaban Plus Aspirin as Compared With Aspirin in Patients With Chronic Vascular Disease.
    Steffel J, Eikelboom JW, Anand SS, Shestakovska O, et al · · 2020 · cited 106× · PMID 32436455 · DOI 10.1161/circulationaha.120.046048

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01776424.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing