Clinical trial NCT04735523: Replication of the RECOVER-II Anticoagulant Trial in Healthcare Claims Data
Official title: Replication of the RECOVER-II Anticoagulant Trial in Healthcare Claims Data
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Venous Thromboembolism
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-02-03
Enrollment: 5350
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will involve a new user, parallel group, propensity score-matched, retrospective cohort study design comparing dabigatran to warfarin users. The patients will be required to have continuous enrollment during a baseline period of 180 days before initiation of dabigatran to warfarin (index date). We will restrict the analyses to patients with a diagnosis of proximal DVT or PE.

Brief summary: Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Detailed description: This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates through standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Eligibility criteria: Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

Eligible cohort entry dates:

Market availability of dabigatran in the U.S. for treatment of deep vein thrombosis and pulmonary embolism started on April 7, 2014

* For Medicare: April 7, 2014 - December 31, 2017 (end of available data)
* For Marketscan: April 7, 2014 - December 31, 2018 (end of available data)
* For Optum: April 7, 2014 - March 31, 2020 (end of available data)

Inclusion Criteria:

* Acute deep vein thrombosis (DVT) of the leg involving proximal veins, and/or pulmonary embolism (PE) iin patients for whom at least 6 months of anticoagulant therapy is considered appropriate.
* Men and women ages 18 years or greater

Exclusion Criteria:

* PE satisfying at least one of the following criteria:

  * Haemodynamic instability
  * OR Embolectomy is indicated or performed
  * OR thrombolytic therapy is indicated or performed
  * OR suspected source of PE is other than blood clots from the legs
* Actual or anticipated use of vena cava filter
* Patients who in the investigators judgement are perceived as having an excessive risk of bleeding
* Known anaemia
* Need of anticoagulant treatment for disorders other than VTE
* Recent unstable cardiovascular disease
* Elevated AST or ALT \> 3x ULN
* Liver disease expected to have any potential impact on survival (severe liver conditions)
* Severe renal impairment
* Contraindications to anticoagulant therapy (not specified)
* Recent or active major bleeding
* Recent brain, eye, or spinal cord injury or surgery
* Malignant or severe, uncontrolled hypertension
* Active infective endocarditis
* Mechanical prosthetic heart valve (recently implanted - RE-ALIGN trial)
* Women who are pregnant, nursing, or of childbearing potential who refuse to use a medically acceptable form of contraception
* Patients who have developed transaminase elevations upon exposure to ximelagatran
* Patients considered unsuitable for inclusion by the investigator

Primary outcomes:
measure: VTE and cause-specific mortality
timeFrame: Through study completion (a median of 84-89 days)
Secondary outcomes:
measure: Hospital admission for VTE
timeFrame: Through study completion (a median of 84-89 days)
measure: Cause-specific mortality
timeFrame: Through study completion (a median of 84-89 days)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shirley Wang, PhD, ScM
role: PRINCIPAL_INVESTIGATOR
References: