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

Idiopathic Venous Thromboembolism Clinical Trial

— REVERSEII  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00967304
• Other study ID #: 2008039-01H
• Status: Completed
• Phase: Phase 4
• First received: August 26, 2009
• Last updated: August 31, 2016
• Start date: November 2008
• Est. completion date: July 2016

Study information

• Verified date: August 2016
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2779
• Est. completion date: July 2016
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Idiopathic Venous Thromboembolism
• Thromboembolism
• Venous Thromboembolism

Intervention

Other:
• Application of the"Men continue and HER DOO2" rule
Consecutive patients will have the"Men 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.

Locations

Country	Name	City	State
Australia	Prince of Wales Hospital	Sydney	New South Wales
Belgium	CUB Hopital Erasme	Brussels
Canada	CDHA-Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Center	Hamilton	Ontario
Canada	Hamilton Health Sciences Corporation	Hamilton	Ontario
Canada	Victoria Hospital	London	Ontario
Canada	Hopital Sacre Coeur	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	SMBD Jewish General Hospital	Montreal	Quebec
Canada	St. Mary's Hospital - CHUM	Montreal	Quebec
Canada	Ottawa Health Research Institute	Ottawa	Ontario
Canada	Hopital Enfant Jesus	Quebec
Canada	Saskatchewan Drug Research Institute	Saskatoon	Saskatchewan
Canada	University Health Network	Toronto	Ontario
France	Centre Hospitalier Regional Universitaire de Brest	Brest
India	Orange Lifesciences	Nirmaya
India	Sahyadri Speciality Hospital	Pune
India	Shefali Centre	Shefali
India	Jashvant Patel Clinic	Surat
Switzerland	Hopitaux Universitaires de Geneve	Geneva
United States	Duke University	Durham	North Carolina
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	UC Davis	Santa Monica	California

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	BioMérieux, Centre Hospitalier Régional et Universitaire de Brest

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  India,  Switzerland, 

References & Publications (1)

Rodger MA, Kahn SR, Wells PS, Anderson DA, Chagnon I, Le Gal G, Solymoss S, Crowther M, Perrier A, White R, Vickars L, Ramsay T, Betancourt MT, Kovacs MJ. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ. 2008 Aug 26;179(5):417-26. doi: 10.1503/cmaj.080493. — View Citation

Outcome

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