Clinical trial NCT00967304: Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Idiopathic Venous Thromboembolism
Keywords: Unprovoked Venous thromboembolism
Clinical decision rule
Anticoagulants
Recurrence
Prognostic
Risk stratification
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: BioMérieux
name: Centre Hospitalier Régional et Universitaire de Brest
First posted: 2009-08-27
Enrollment: 2779
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: One year
Secondary outcomes:
measure: Any VTE 1 year event rate in low risk patients
timeFrame: One year
measure: Major bleeding 1 year event rate in un-anticoagulated low risk patients
timeFrame: One year
measure: Major VTE 1 year event rate in high risk patients who continue anticoagulant therapy
timeFrame: One year
measure: Major VTE 1 year event rate in high risk patients who discontinue anticoagulant therapy
timeFrame: One year
measure: Major Bleeding 1 year event rate in high risk patients
timeFrame: One year
measure: Clinical utility of the rule
timeFrame: One year
measure: Inter-observer reliability of the clinical decision rule
timeFrame: One year
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UC Davis
state: California
city: Rockport
country: United States
facility: Penobscot Bay Medical Center
state: Maine
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Brussels
country: Belgium
facility: CUB Hopital Erasme
city: Halifax
country: Canada
facility: CDHA-Queen Elizabeth II Health Science Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Center
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: SMBD Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sacre Coeur
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montreal
country: Canada
facility: St. Mary's Hospital - CHUM
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatchewan Drug Research Institute
state: Saskatchewan
city: Quebec
country: Canada
facility: Hopital Enfant Jesus
city: Brest
country: France
facility: Centre Hospitalier Regional Universitaire de Brest
city: Nirmaya
country: India
facility: Orange Lifesciences
city: Pune
country: India
facility: Sahyadri Speciality Hospital
city: Shefali
country: India
facility: Shefali Centre
city: Surat
country: India
facility: Jashvant Patel Clinic
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Marc Rodger, MD, MSc
role: STUDY_CHAIR
References:
citation: 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.
citation: Rodger MA, Le Gal G, Anderson DR, Schmidt J, Pernod G, Kahn SR, Righini M, Mismetti P, Kearon C, Meyer G, Elias A, Ramsay T, Ortel TL, Huisman MV, Kovacs MJ; REVERSE II Study Investigators. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ. 2017 Mar 17;356:j1065. doi: 10.1136/bmj.j1065.