The DARE Warfarin CER Study

NCT03271450 | Unknown

• 1 other identifier: 2017P000215
• Study Type: observational
• Target: 416,000
• Locations: 1 country
• Sites: 1

Brief Summary

Approximately half a million Americans annually experience venous thromboembolic disease, including deep venous thrombosis (DVT) and pulmonary embolism (PE). Since 2010, four new oral anticoagulants have been approved for marketing in addition to the vitamin K antagonist warfarin. Very limited head-to-head data exists comparing these treatment options, leaving patients, clinicians, and other stakeholders with little guidance for selecting the best strategy that balances recurrence reduction with risk of bleeding. In the DARE Warfarin CER Study, the researchers compare all five currently available oral anticoagulant agents for the extended treatment of DVT and PE, as well as no extended treatment. This study also aims to evaluate whether treatment heterogeneity exists for specific populations, such as older patients or those with renal dysfunction. In a secondary aim, the study will also leverage a database of linked electronic health record-insurance claims to validate diagnosis definitions and account for potential residual confounding by factors unmeasured in claims data. As the patient population includes all Medicare novel anticoagulant users and large numbers of commercially insured and Medicaid patients, the results will likely be transportable to the majority of US patients experiencing a DVT or PE. Pursuant to the objectives of the Patient-Centered Outcomes Research Institute, a study advisory committee consisting of key stakeholders will be actively involved in the study design and dissemination of results.

Conditions

Deep Venous Thrombosis; Pulmonary Embolism

Keywords

dabigatran; warfarin; apixaban; edoxaban; extended treatment; oral anticoagulant; rivaroxaban; comparative safety; comparative effectiveness

Outcome Measures

Primary Outcomes (5)

• Composite Safety Outcome: Intracranial bleed, Gastrointestinal bleed, Other Major bleed

  Defined as a new episode of either Intracranial bleed, Gastrointestinal bleed or another Major bleed event during follow-up.

  1-2 Years

• Composite Effectiveness Outcome: Deep Venous Thrombosis, Pulmonary Embolism

  Defined as a new episode of either Deep Venous Thrombosis or Pulmonary Embolism during follow-up.

  1-2 Years

• Death

  Measured after index prescription date + 90 days and on date on which the event occurred and defined as hospitalization with discharge status code of: 20, 22-29, 40-42

  1-2 Years

• Composite safety and effectiveness outcome

  defined as earlier of safety or DVT/PE outcomes

  1-2 years

• Composite safety and effectiveness outcome, including death

  Measured after index prescription date + 90 days and on date on which the event occurred and defined as hospitalization with discharge status code of: 20, 22-29, 40-42

  1-2 years

Study Arms (30)

Continuer at 90 Days: Dabigatran

Drug: Dabigatran: extended treatment (e.g at least 90 days)

Continuer at 180 Days: Dabigatran

Drug: Dabigatran: extended treatment (e.g at least 180 days)

Continuer at 270 Days: Dabigatran

Drug: Dabigatran: extended treatment (e.g at least 270 days)

Continuer at 90 Days: Apixaban

Drug: Apixaban: extended treatment (e.g at least 90 days)

Continuer at 180 Days: Apixaban

Drug: Apixaban: extended treatment (e.g at least 180 days)

Continuer at 270 Days: Apixaban

Drug: Apixaban: extended treatment (e.g at least 270 days)

Continuer at 90 Days: Rivaroxaban

Drug: Rivaroxaban: extended treatment (e.g at least 90 days)

Continuer at 180 Days: Rivaroxaban

Drug: Rivaroxaban: extended treatment (e.g at least 180 days)

Continuer at 270 Days: Rivaroxaban

Drug: Rivaroxaban: extended treatment (e.g at least 270 days)

Continuer at 90 Days: Edoxaban

Drug: Edoxaban: extended treatment (e.g at least 90 days)

Continuer at 180 Days: Edoxaban

Drug: Edoxaban: extended treatment (e.g at least 180 days)

Continuer at 270 Days: Edoxaban

Drug: Edoxaban: extended treatment (e.g at least 270 days)

Continuer at 90 Days: Warfarin

Drug: Warfarin: extended treatment (e.g at least 90 days)

Continuer at 180 Days: Warfarin

Drug: Warfarin: extended treatment (e.g at least 180 days)

Continuer at 270 Days: Warfarin

Drug: Warfarin: extended treatment (e.g at least 270 days)

Discontinuer at 90 Days: Dabigatran

Drug: Dabigatran: extended treatment (e.g at least 90 days)

Discontinuer at 180 Days: Dabigatran

Drug: Dabigatran: extended treatment (e.g at least 180 days)

Discontinuer at 270 Days: Dabigatran

Drug: Dabigatran: extended treatment (e.g at least 270 days)

Discontinuer at 90 Days: Apixaban

Drug: Apixaban: extended treatment (e.g at least 90 days)

Discontinuer at 180 Days: Apixaban

Drug: Apixaban: extended treatment (e.g at least 180 days)

Discontinuer at 270 Days: Apixaban

Drug: Apixaban: extended treatment (e.g at least 270 days)

Discontinuer at 90 Days: Rivaroxaban

Drug: Rivaroxaban: extended treatment (e.g at least 90 days)

Discontinuer at 180 Days: Rivaroxaban

Drug: Rivaroxaban: extended treatment (e.g at least 180 days)

Discontinuer at 270 Days: Rivaroxaban

Drug: Rivaroxaban: extended treatment (e.g at least 270 days)

Discontinuer at 90 Days: Edoxaban

Drug: Edoxaban: extended treatment (e.g at least 90 days)

Discontinuer at 180 Days: Edoxaban

Drug: Edoxaban: extended treatment (e.g at least 180 days)

Discontinuer at 270 Days: Edoxaban

Drug: Edoxaban: extended treatment (e.g at least 270 days)

Discontinuer at 90 Days: Warfarin

Drug: Warfarin: extended treatment (e.g at least 90 days)

Discontinuer at 180 Days: Warfarin

Drug: Warfarin: extended treatment (e.g at least 180 days)

Discontinuer at 270 Days: Warfarin

Drug: Warfarin: extended treatment (e.g at least 270 days)

Interventions

Dabigatran: extended treatment (e.g at least 90 days) DRUG

90 days

Continuer at 90 Days: Dabigatran; Discontinuer at 90 Days: Dabigatran

Dabigatran: extended treatment (e.g at least 180 days) DRUG

180 days

Continuer at 180 Days: Dabigatran; Discontinuer at 180 Days: Dabigatran

Dabigatran: extended treatment (e.g at least 270 days) DRUG

270 days

Continuer at 270 Days: Dabigatran; Discontinuer at 270 Days: Dabigatran

Apixaban: extended treatment (e.g at least 90 days) DRUG

90 days

Continuer at 90 Days: Apixaban; Discontinuer at 90 Days: Apixaban

Apixaban: extended treatment (e.g at least 180 days) DRUG

180 days

Continuer at 180 Days: Apixaban; Discontinuer at 180 Days: Apixaban

Apixaban: extended treatment (e.g at least 270 days) DRUG

270 days

Continuer at 270 Days: Apixaban; Discontinuer at 270 Days: Apixaban

Rivaroxaban: extended treatment (e.g at least 90 days) DRUG

90 days

Continuer at 90 Days: Rivaroxaban; Discontinuer at 90 Days: Rivaroxaban

Rivaroxaban: extended treatment (e.g at least 180 days) DRUG

180 days

Continuer at 180 Days: Rivaroxaban; Discontinuer at 180 Days: Rivaroxaban

Rivaroxaban: extended treatment (e.g at least 270 days) DRUG

270 days

Continuer at 270 Days: Rivaroxaban; Discontinuer at 270 Days: Rivaroxaban

Edoxaban: extended treatment (e.g at least 90 days) DRUG

90 days

Continuer at 90 Days: Edoxaban; Discontinuer at 90 Days: Edoxaban

Edoxaban: extended treatment (e.g at least 180 days) DRUG

180 days

Continuer at 180 Days: Edoxaban; Discontinuer at 180 Days: Edoxaban

Edoxaban: extended treatment (e.g at least 270 days) DRUG

270 days

Continuer at 270 Days: Edoxaban; Discontinuer at 270 Days: Edoxaban

Warfarin: extended treatment (e.g at least 90 days) DRUG

90 days

Continuer at 90 Days: Warfarin; Discontinuer at 90 Days: Warfarin

Warfarin: extended treatment (e.g at least 180 days) DRUG

180 days

Continuer at 180 Days: Warfarin; Discontinuer at 180 Days: Warfarin

Warfarin: extended treatment (e.g at least 270 days) DRUG

270 days

Continuer at 270 Days: Warfarin; Discontinuer at 270 Days: Warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cohort derived from a commercial database, MarketScan, and Medicare Research Identifiable Files using data from 2009-2015. Cohort data will be updated as new data come in through 2019.

You may qualify if:

• Inpatient stay with diagnosis code of DVT/PE (see Appendix A), 1/1/2010 - 9/30/2015 for which the patient has at least 365 days continuous medical and pharmacy eligibility prior and no other inpatient stays with DVT/PE diagnosis. Set discharge date as index diagnosis date. Take only the first eligible episode for a patient, if multiple.
• Prescription fill for an anticoagulant \[generic name=dabigatran (150mg), apixaban (2.5mg, 5mg, 10mg), rivaroxaban (15mg, 20mg), edoxaban (30mg, 60mg), or warfarin\] within 30 days of and including index diagnosis date. Set earliest anticoagulant prescription as index generic and date as index rx date.
• No anticoagulant prescription fill in the 365 days prior to index diagnosis date.
• Continuous enrollment and use of an anticoagulant for the first 90 days including and following the index rx date, defined as no gaps in therapy \>7 days. For each patient, assign a variable to indicate whether the patient filled an anticoagulant with a different generic name as index during this period.

You may not qualify if:

• Any safety outcome between index diagnosis date and index rx date + 90, defined as: intracranial bleed, gastrointestinal bleed, or other major bleed.
• Any DVT/PE between index diagnosis date and index rx date + 90.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Harvard Medical School (HMS and HSDM): collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• Krumme AA, Pawar A, Schneeweiss S, Glynn RJ, Choudhry NK, Kulldorff M, Ortiz AS, Avorn J, Gagne JJ. Study protocol for the dabigatran, apixaban, rivaroxaban, edoxaban, warfarin comparative effectiveness research study. J Comp Eff Res. 2018 Jan;7(1):57-66. doi: 10.2217/cer-2017-0053. Epub 2017 Dec 21.

  PMID: 29264930 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Pulmonary Embolism

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: September 5, 2017
• Study Start: July 1, 2017
• Primary Completion: October 30, 2021
• Study Completion: October 30, 2021
• Last Updated: June 23, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)