Idiopathic Venous ThromboembolismPhase 4REVERSEIINCT00967304
Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
A Phase 4 study testing Application of the"Men continue and HER DOO2" rule in people with Idiopathic Venous Thromboembolism, run by Ottawa Hospital Research Institute at 23 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Venous Thromboembolism
- What is being tested?
- Application of the"Men continue and HER DOO2" rule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,779 participants
- Where
- 23 sitesin 7 countries
- Study dates
- Nov 2008to Jul 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Patients with pregnancy associated VTE
- Geographically inaccessible for follow-up
- Patients unable or unwilling to provide informed consent
Trial locations and contacts
23 sites in 7 countries.
23 sites in 7 countries
Canada12 sites
CDHA-Queen Elizabeth II Health Science Centre
Halifax, Nova Scotia, B3H2Y9
Hamilton Health Sciences Center
Hamilton, Ontario
Hamilton Health Sciences Corporation
Hamilton, Ontario
Victoria Hospital
London, Ontario, N6A 4G5
SMBD Jewish General Hospital
Montreal, Quebec, H3T 1E2
Hopital Sacre Coeur
Montreal, Quebec
McGill University Health Centre
Montreal, Quebec
St. Mary's Hospital - CHUM
Montreal, Quebec
Ottawa Health Research Institute
Ottawa, Ontario, K1Y 4E9
Hopital Enfant Jesus
Québec, Quebec
Saskatchewan Drug Research Institute
Saskatoon, Saskatchewan, S7N 0W8
University Health Network
Toronto, Ontario
India4 sites
Orange Lifesciences
Nirmaya
Sahyadri Speciality Hospital
Pune
Shefali Centre
Shefali
Jashvant Patel Clinic
Surat
United States3 sites
Duke University
Durham, North Carolina, 27705
Penobscot Bay Medical Center
Rockport, Maine
UC Davis
Santa Monica, California
About this study
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.
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.
Read the 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.
- Conditions
- Idiopathic Venous Thromboembolism
- Being tested
- Application of the"Men continue and HER DOO2" rule
- Keywords
- Unprovoked Venous thromboembolism, Clinical decision rule, Anticoagulants, Recurrence, Prognostic, Risk stratification
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Application of the"Men continue and HER DOO2" ruleOther
Also called Clinical Decision 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.
| Study group | Role | What they receive |
|---|---|---|
| 1 Discontinue OAT or AAA | Experimental | 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. Receives: Other: Application of the"Men continue and HER DOO2" rule |
| 2 Observation arm | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: One year
Secondary outcomes (7)
Any VTE 1 year event rate in low risk patients
Measured: One year
Major bleeding 1 year event rate in un-anticoagulated low risk patients
Measured: One year
Major VTE 1 year event rate in high risk patients who continue anticoagulant therapy
Measured: One year
Major VTE 1 year event rate in high risk patients who discontinue anticoagulant therapy
Measured: One year
Major Bleeding 1 year event rate in high risk patients
Measured: One year
Clinical utility of the rule
Measured: One year
Inter-observer reliability of the clinical decision rule
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2009 (estimated)
- Study startNov 2008
- Primary completionJan 2015
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,779 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- BioMérieux, Centre Hospitalier Régional et Universitaire de Brest
- Responsible party
- Sponsor
- Investigators
- Marc Rodger, MD, MSc, Study chair, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00967304
- Sponsor's protocol ID
- 2008039-01H
- Acronym
- REVERSEII
- Status last verified
- Aug 2016
- First submitted
- 26 Aug 2009
- Last updated
- 1 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 18725614Rodger 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.
PubMed 28314711
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00967304
- Acronym / sponsor ID
- REVERSEII / 2008039-01H
- Conditions
- Idiopathic Venous Thromboembolism
- Keywords
- Unprovoked Venous thromboembolism, Clinical decision rule, Anticoagulants, Recurrence, Prognostic, Risk stratification
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,779 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- BioMérieux, Centre Hospitalier Régional et Universitaire de Brest
- Study start
- Nov 2008
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 27 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Discontinue OAT or AAA | Experimental | Other: Application of the"Men continue and HER DOO2" rulePatients 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. |
| 2 Observation arm | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Application of the"Men continue and HER DOO2" ruleAlso: Clinical Decision RuleConsecutive 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 | 1 Discontinue OAT or AAA |
Primary outcome
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
7 secondary outcomes
Any VTE 1 year event rate in low risk patients
Time frame: One year
Major bleeding 1 year event rate in un-anticoagulated low risk patients
Time frame: One year
Major VTE 1 year event rate in high risk patients who continue anticoagulant therapy
Time frame: One year
Major VTE 1 year event rate in high risk patients who discontinue anticoagulant therapy
Time frame: One year
Major Bleeding 1 year event rate in high risk patients
Time frame: One year
Clinical utility of the rule
Time frame: One year
Inter-observer reliability of the clinical decision rule
Time frame: One year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
- Background: PubMed 18725614Rodger 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.
- Derived from this study: PubMed 28314711Rodger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Rodger, MD, MSc study chair
Ottawa Hospital Research Institute
23 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Application of the"Men continue and HER DOO2" rule in people with Idiopathic Venous Thromboembolism, run by Ottawa Hospital Research Institute at 23 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Canada, India, United States, Australia, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00967304, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2016.