Clinical trial NCT03050138: Prevalence of Post-Thrombotic Syndrome in Deep-Vein Thrombosis (DVT) Patients Treated With Dabigatran
Official title: The Prevalence of Post-Thrombotic Syndrome in Deep-Vein Thrombosis (DVT) Patients Treated With Dabigatran- a Cross-Sectional Assessment of RE-COVER Study Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postthrombotic Syndrome
Keywords: Postthrombotic Syndrome
Venous Thrombosis
Quality of Life
Hemorrhage
Recurrence
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Ostfold Hospital Trust
name: St. Olavs Hospital
name: Vestre Viken Hospital Trust
name: Sahlgrenska University Hospital
name: Kristianstad University
name: Jewish General Hospital
name: McMaster University
First posted: 2017-02-10
Enrollment: 351
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients participating in the RE-COVER- and RE-COVER II studies in Canada, Norway, Sweden, and Denmark will be invited to participate in this investigator initiated follow-up study. In the original studies patients with DVT and/or PE were randomized to receive 6 months of treatment with either dabigatran (150 mg twice daily) or warfarin (once daily to maintain international normalized ratio (INR) 2.0-3.0). All patients received an initial 5-7 day phase of parenteral anticoagulant treatment. The studies were designed as double blind, double dummy trials. RE-COVER was conducted between April 2006 to November 2008 and RE-COVER II between June 2008 and October 2010; they were completed in 2009 and 2011, respectively. The present study is a cross-sectional study.

Brief summary: The primary objective in this cross-sectional study is to assess the prevalence of post-thrombotic syndrome (PTS) in the two treatment arms of the RE-COVER studies (warfarin versus dabigatran). PTS will be assessed by the recently developed Patient Reported Villalta (PRV) Score.

Secondary objectives: to assess in both treatment arms the

1. Prevalence of recurrent venous thromboembolism (VTE) after the discontinuation of study treatment.
2. Prevalence of PTS determined by the standard Villalta score.
3. Health related Quality of Life (HRQoL).

Detailed description: In the RE-COVER- and RE-COVER II studies, 5109 patients with deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) were randomized to receive 6 months of treatment with either dabigatran (150 mg twice daily) or warfarin (once daily to maintain international normalized ratio (INR) 2.0-3.0). All patients received an initial 5-7 day phase of parenteral anticoagulant treatment. The studies were designed as double blind, double dummy trials. RE-COVER was conducted between April 2006 to November 2008 and RE-COVER II between June 2008 and October 2010; they were completed in 2009 and 2011, respectively. A substantial number of patients are expected to have developed post-thrombotic syndrome (PTS). However, since dabigatran provides a stable level of anticoagulation throughout the treatment period and knowing that the quality of anticoagulation is an important factor in the development of PTS, we anticipate that a lower rate of PTS will be seen in the dabigatran treated patients compared to warfarin.

Patients will be interviewed and examined by the investigator if they accept to attend a clinic visit. Otherwise, a telephone interview will be performed if the patient refuses to meet up. PTS will be determined using Patient Reported Villalta (PRV) Score form. However, those who will meet for consultation will in addition be assessed for PTS by the standard Villalta score.

The primary endpoint will be the prevalence of PTS determined by Patient Reported Villalta (PRV) score. The secondary endpoints are 1- objectively verified DVT or PE after the discontinuation of treatment, 2- prevalence of PTS determined by the standard Villalta score, 3- health related quality of life (HRQOL) determined by EQ-5D (www.euroqol.org) and Venous Insufficiency Epidemiological and Economic Study quality of life and symptom (VEINES-QOL/Sym) questionnaires.

The investigators will recruit the subpopulation of patients who were included into the RE-COVER studies in the Norway, Sweden and Canada.

Eligibility criteria: Inclusion Criteria:

1. Patients with DVT (±PE) treated in the RE-COVER studies.
2. Signed written informed consent.

Exclusion Criteria:

1. Patients who refuse to participate
2. Deceased patients

Primary outcomes:
measure: Post-thrombotic syndrome (PTS)
timeFrame: April 2016 - December 2017
Secondary outcomes:
measure: Recurrent venous thromboembolism
timeFrame: April 2016 - December 2017
measure: Post-thrombotic syndrome (PTS) determined by the standard Villalta score
timeFrame: April 2016 - December 2017
measure: Generic health related Quality of Life (HRQoL)
timeFrame: April 2016 - December 2017
measure: Disease specific health related Quality of Life (HRQoL)
timeFrame: April 2016 - December 2017
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Oslo
country: Norway
facility: Oslo University Hospital Rikshospitalet
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset/Östra
Study officials:
affiliation: Oslo University Hospital
name: Hilde S Wik, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Utne KK, Ghanima W, Foyn S, Kahn S, Sandset PM, Wik HS. Development and validation of a tool for patient reporting of symptoms and signs of the post-thrombotic syndrome. Thromb Haemost. 2016 Jan;115(2):361-367. doi: 10.1160/th15-04-0318. Epub 2015 Sep 17.
citation: Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. doi: 10.1056/NEJMoa0906598.
citation: Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. doi: 10.1161/CIRCULATIONAHA.113.004450. Epub 2013 Dec 16.