Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism (REVERSEII)

Ottawa Hospital Research Institute

Status and phase: Completed; Phase 4

Conditions: Idiopathic Venous Thromboembolism

Treatments: Other: Application of the"Men continue and HER DOO2" rule

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00967304

2008039-01H

Details and patient eligibility

About

The main objective of this study is to verify whether a new clinical decision rule identifying patients diagnosed with unprovoked blood clots who have a low risk of recurrence can safely stop oral anticoagulant therapy after 5-7 months of treatment.

Full description

Up to 50% of patients with a first episode of venous thromboembolism (VTE) have no identifiable cause (i.e. are unprovoked VTEs). The risk of recurrent VTE in this large group of patients with unprovoked VTE after 3-6 months of anticoagulant therapy is 5-10.8% in the year following discontinuation of oral anticoagulant therapy. One in six to one in twenty recurrences of a new VTE are fatal. Given the intermediate risks of recurrence in unselected unprovoked VTE patients, clinicians do not have clear guidance on whether to continue or discontinue anticoagulants in patients with unprovoked VTE. Recently attention has turned to the concept of risk stratification to identify subgroups of patients with unprovoked VTE who could safely discontinue oral anticoagulation therapy (OAT).

In the REVERSE I study, a clinical decision rule derivation study conducted from 2001 to 2006, we developed and internally validated the clinical decision rule "Men continue and HER DOO2" that identifies patients with a first unprovoked VTE who likely have a low risk of recurrent VTE and could safely discontinue OAT subsequent to 5-7 months of OAT. The present study will evaluate if the "Men continue and HER DOO2" rule (comprised of gender, elevated D-dimer levels, post-thrombotic signs, obesity, and older age) is safe, clinically useful, and reproducible when prospectively implemented in multiple centers and a variety of settings. If this clinical decision rule is validated, it will provide physicians with important information to allow them to more confidently identify unprovoked VTE patients at low risk of VTE recurrence who may not need to continue OAT.

Enrollment: 2,779 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• First episode of major unprovoked VTE
• VTE objectively proven
• VTE treated for 5-12 months with anticoagulant therapy authorized for the REVERSE II study (initial or ongoing therapy)
• Absence of recurrent VTE during the treatment period

Exclusion criteria

• Less than 18 years of age
• Patients who have already discontinued anticoagulant therapy
• Patients requiring ongoing anticoagulation for reasons other than VTE
• Being treated for a recurrent unprovoked VTE
• Patients with high risk thrombophilia
• patients who plan on using exogenous estrogen(OCP,HRT)if anticoagulant therapy is discontinued
• Patients with pregnancy associated VTE
• Geographically inaccessible for follow-up
• Patients unable or unwilling to provide informed consent

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,779 participants in 2 patient groups

1 Discontinue OAT or AAA

Experimental group

Description:

Patients classified as being at low risk of recurrent VTE by the "HER DOO2"rule. If the clinical decision rule indicates that a patient is at low recurrence risk (\<3% per year); anticoagulant therapy will be withdrawn and the participant will then be followed for 1 year for any VTE recurrence and/or bleeding.

Treatment:

Other: Application of the"Men continue and HER DOO2" rule

2 Observation arm

No Intervention group

Description:

Men and patients classified as being at high risk of recurrent VTE by the "HER DOO2"rule. If the clinical decision rule indicates that a patient is at high recurrence risk then the decision to continue or discontinue anticoagulant therapy will be left to the discretion of physicians and patients as per current standard of care and this decision recorded. High risk patients (females classified as being at high risk of recurrent VTE by the CDR, and all males) will then be followed as an observational cohort for 1 year for any VTE recurrence and/or bleeding.