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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Biomerieux
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00967304
First received: August 26, 2009
Last updated: March 2, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Idiopathic Venous Thromboembolism
Other: Application of the"Men continue and HER DOO2" rule
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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.

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • 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. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Any VTE 1 year event rate in low risk patients [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Major bleeding 1 year event rate in un-anticoagulated low risk patients [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Major VTE 1 year event rate in high risk patients who continue anticoagulant therapy [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Major VTE 1 year event rate in high risk patients who discontinue anticoagulant therapy [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Major Bleeding 1 year event rate in high risk patients [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Clinical utility of the rule [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Inter-observer reliability of the clinical decision rule [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment: 3312
Study Start Date: November 2008
Estimated Study Completion Date: January 2016
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Discontinue OAT or AAA

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.

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.

Other Name: Clinical Decision Rule
No Intervention: 2 Observation arm

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.


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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967304

Locations
United States, California
UC Davis
Santa Monica, California, United States
United States, Maine
Penobscot Bay Medical Center
Rockport, Maine, United States
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
Australia, New South Wales
Prince of Wales Hospital
Sydney, New South Wales, Australia
Belgium
CUB Hopital Erasme
Brussels, Belgium
Canada, Nova Scotia
CDHA-Queen Elizabeth II Health Science Centre
Halifax, Nova Scotia, Canada, B3H2Y9
Canada, Ontario
Hamilton Health Sciences Center
Hamilton, Ontario, Canada
Hamilton Health Sciences Corporation
Hamilton, Ontario, Canada
Victoria Hospital
London, Ontario, Canada, N6A 4G5
Ottawa Health Research Institute
Ottawa, Ontario, Canada, K1Y 4E9
University Health Network
Toronto, Ontario, Canada
Canada, Quebec
St. Mary's Hospital - CHUM
Montreal, Quebec, Canada
McGill University Health Centre
Montreal, Quebec, Canada
SMBD Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Hopital Sacre Coeur
Montreal, Quebec, Canada
Canada, Saskatchewan
Saskatchewan Drug Research Institute
Saskatoon, Saskatchewan, Canada, S7N 0W8
Canada
Hopital Enfant Jesus
Quebec, Canada
France
Centre Hospitalier Regional Universitaire de Brest
Brest, France
India
Orange Lifesciences
Nirmaya, India
Sahyadri Speciality Hospital
Pune, India
Shefali Centre
Shefali, India
Jashvant Patel Clinic
Surat, India
Switzerland
Hopitaux Universitaires de Geneve
Geneva, Switzerland
Sponsors and Collaborators
Ottawa Hospital Research Institute
Biomerieux
Investigators
Study Chair: Marc Rodger, MD, MSc Ottawa Hospital Research Institute
  More Information

Publications:
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00967304     History of Changes
Other Study ID Numbers: 2008039-01H
Study First Received: August 26, 2009
Last Updated: March 2, 2015
Health Authority: Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
Unprovoked Venous thromboembolism
Clinical decision rule
Anticoagulants
Recurrence
Prognostic
Risk stratification

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Thrombosis
Vascular Diseases
Anticoagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 30, 2015