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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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REVERSEII: Validation of the Men and HERDOO2- A Clinical Decision Rule to Identify Patients With Unprovoked Venous Thromboembolism Who Can Discontinue Anticoagulants After 6 Months of Treatment.

Conditions
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Idiopathic Venous Thromboembolism

Intervention / Treatment
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* Other: Application of theMen continue and HER DOO2 rule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Discontinue OAT or AAA<br>Patients classified as being at low risk of recurrent VTE by the HER DOO2rule. 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. | Other: Application of theMen continue and HER DOO2 rule<br>* Consecutive patients will have theMen continue and HER DOO2 rule applied by the attending physician between 5 - 12 months after treatment for a first unprovoked objectively proven major VTE. Men continue and HER DOO2 rule: all men continue oral anticoagulants and women with 2 or more of the following features after 5-7 months of OAT should continue oral anticoagulants:1) HER - any Hyperpigmentation, Edema and Redness of either lower extremity, 2) Vidas D-dimer ≥250ug/L, 3) Obesity - BMI ≥30 kg/m2 and 4) Older age - Age ≥65 years.<br>* Other names: Clinical Decision Rule;|
| No Intervention: 2 Observation arm<br>Men and patients classified as being at high risk of recurrent VTE by the HER DOO2rule. 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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary study outcome is the incidence of adjudicated recurrent major VTE at 1 year in patients deemed by the Men and HER DOO2 CDR to be at low risk of recurrent VTE. |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any VTE 1 year event rate in low risk patients |  | One year | 
| Major bleeding 1 year event rate in un-anticoagulated low risk patients |  | One year | 
| Major VTE 1 year event rate in high risk patients who continue anticoagulant therapy |  | One year | 
| Major VTE 1 year event rate in high risk patients who discontinue anticoagulant therapy |  | One year | 
| Major Bleeding 1 year event rate in high risk patients |  | One year | 
| Clinical utility of the rule |  | One year | 
| Inter-observer reliability of the clinical decision rule |  | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unprovoked Venous thromboembolism, Clinical decision rule, Anticoagulants, Recurrence, Prognostic, Risk stratification