Prevalence of Post-Thrombotic Syndrome in Deep-Vein Thrombosis (DVT) Patients Treated With Dabigatran (DABI-PTS)

The Prevalence of Post-Thrombotic Syndrome in Deep-Vein Thrombosis (DVT) Patients Treated With Dabigatran- a Cross-Sectional Assessment of RE-COVER Study Patients

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).

Study Overview

• Status: Completed
• Conditions: Postthrombotic Syndrome

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.

• Study Type: Observational
• Enrollment (Actual): 351

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L8E7
      • Hamilton Health Sciences Corporation
• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital Rikshospitalet
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset/Östra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Dabigatran; In the RE-COVER- and RE-COVER II studies, one group of DVT and/or PE patients were randomized to receive 6 months of treatment with dabigatran (150 mg twice daily). All patients received an initial 5-7 day phase of parenteral anticoagulant treatment.
Warfarin; In the RE-COVER- and RE-COVER II studies, the other group of DVT and/or PE patients were randomized to receive 6 months of treatment with 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-thrombotic syndrome (PTS)	The primary objective is to assess the prevalence of PTS in a subgroup of patients in the two treatment arms of the RE-COVER studies assessed by Patient Reported Villalta (PRV) Score.	April 2016 - December 2017

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent venous thromboembolism	Prevalence of recurrent VTE after the discontinuation of study treatment in a subgroup of patients in the two treatment arms of the RE-COVER studies.	April 2016 - December 2017
Post-thrombotic syndrome (PTS) determined by the standard Villalta score	Prevalence of PTS determined by the standard Villalta score in a subgroup of patients in the two treatment arms of the RE-COVER studies.	April 2016 - December 2017
Generic health related Quality of Life (HRQoL)	Generic health related Quality of Life (HRQoL) assessed by the EQ-5D in a subgroup of patients in the two treatment arms of the RE-COVER studies.	April 2016 - December 2017
Disease specific health related Quality of Life (HRQoL)	Disease specific health related Quality of Life (HRQoL) assessed by the VEINES-QOL/Sym score in a subgroup of patients in the two treatment arms of the RE-COVER studies.	April 2016 - December 2017

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Vestre Viken Hospital Trust; McMaster University; Ostfold Hospital Trust; Sahlgrenska University Hospital, Sweden; St. Olavs Hospital; Jewish General Hospital; Kristianstad University
• Investigators: Principal Investigator: Hilde S Wik, MD, PhD, Oslo University Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2016
• Primary Completion (ACTUAL): January 31, 2019
• Study Completion (ACTUAL): January 31, 2019

Study Registration Dates

• First Submitted: February 8, 2017
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (ACTUAL): February 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Quality of Life; Recurrence; Hemorrhage; Venous Thrombosis; Postthrombotic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease; Embolism and Thrombosis; Peripheral Vascular Diseases; Venous Insufficiency; Phlebitis; Syndrome; Thrombosis; Venous Thrombosis; Postthrombotic Syndrome; Postphlebitic Syndrome
• Other Study ID Numbers: 2014/151

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No