Venous Thromboembolism
Conditions
Keywords
Proximal Lower Extremity Deep Vein Thrombosis, Randomized Trial, Colchicine, Post Thrombotic Syndrome, Inflammation
Brief summary
This trial seeks to assess the feasibility of a full-scale, double-blind, placebo-controlled, randomized trial assessing whether low-dose colchicine (0.5 mg daily) reduces the risk of post-thrombotic syndrome (PTS) in patients with proximal lower extremity deep vein thrombosis (DVT).
Detailed description
Eligible and consenting patients will be randomized via a central web-based randomization system (1:1 ratio) to receive one tablet of colchicine 0.5 mg or identical matching placebo daily starting within 7 days of initiation of anticoagulation for acute, symptomatic, proximal lower extremity Deep Vein Thrombosis (DVT) for a treatment course of 180 days (+/- 7 days). Study drug will start within 24 hours of randomization. The type, dose, and duration of anticoagulant therapy : unfractionated heparin, Low Molecular Weight Heparin (LMWH), fondaparinux, Direct Oral Anticoagulation (DOAC) or Vitamin K Agonist (VKA) will be left to the discretion of the treating physician or local investigator. The study drug will be continued until the end of the treatment period (180 days +/- 7 days). All patients will be observed until the end of study follow-up (365 days +/- 7 days).
Interventions
DRUGColchicine 0.5 mg po
Colchicine 0.5 mg po once daily for 180 days.
DRUGPlacebo 0.5 mg po
Placebo 0.5 mg po once daily for 180 days.
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized Controlled Pilot Trial comparing two groups - Colchicine 0.5 mg po once daily for 180 days vs Placebo 0.5 mg po once daily for 180 days.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Consenting patients 18 years of age or older with a first, acute, symptomatic proximal (popliteal vein or more proximal) objectively confirmed DVT of the lower extremity will be eligible to participate in the study.
Exclusion criteria
1. History of an allergic reaction or significant sensitivity to colchicine. 2. Requirement of colchicine for other indications. 3. Active or chronic diarrhea, or documented inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis), collagenous colitis or irritable bowel syndrome or existing blood dyscrasias. 4. Known or suspected, recent (\<30 days) or active infections (acute or chronic). 5. History of cirrhosis, chronic active hepatitis, or severe liver disease. 6. Recent (\<30 days) or chronic use of systemic (oral, intravenous) immunosuppressive drugs (including but not limited to steroids, tumor necrosis factor-alpha blockers, cyclosporine). 7. Known active cancer. 8. Any of the following as measured within the past 1-3 months or at screening: alanine, or aspartate aminotransferase \>3 times the upper limit of normal, total bilirubin \>2 times the upper limit of normal and a creatinine clearance by Cockcroft-Gault formula \<30 mL/min. 9. Pregnancy, breast feeding or may be considering pregnancy during the study period or women of childbearing potential unwilling to use appropriate contraception during sex; 10. The use of medication with known drug-to-drug interactions (including but not limited to erythromycin or clarithromycin). 11. Unable or unwilling to provide consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pilot Trial Primary Outcome: Recruitment Rate | 12 months | Mean number of participants recruited per site per month |
| Full-Scale Trial Primary Outcome: Post Thrombotic Syndrome | 180 days | VILLALTA scale score ≥5 signifies clinically meaningful Post Thrombotic Syndrome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pilot Trial Secondary Outcome: Eligibility Rate | 12 months | Proportion of screened patients who are eligible |
| Pilot Trial Secondary Outcome: Consent Rate | 12 months | Proportion of eligible patients who provide consent |
| Pilot Trial Secondary Outcome: Retention Rate | 12 months | Proportion of participants retained at follow-up |
| Pilot Trial Secondary Outcome: Study Completion Rate | 12 months | Proportion of participants who completed all study procedures |
| Pilot Trial Secondary Outcome: Adherence Rate | 12 months | Adherence to study drug measured by pill count at the end of follow-up |
| Pilot Trial Secondary Outcome: Reasons for declining participation | 12 months | Pilot Trial Secondary Outcome: Reasons for declining participation |
| Full-Scale Trial Secondary Outcome: Post Thrombotic Syndrome | 365 days | VILLALTA scale score ≥5 signifies clinically meaningful Post Thrombotic Syndrome |
| Full-Scale Trial Secondary Outcome: Severe Post Thrombotic Syndrome | 180 and 365 days | VILLALTA scale score ≥ 15 signifies significant clinically meaningful Post Thrombotic Syndrome or presence of ulcer will be collected |
| Full-Scale Trial Secondary Outcome: Severity of Post Thrombotic Syndrome | 180 and 365 days | Continuous VILLALTA score (VILLALTA scale score ≥5 signifies clinically meaningful Post Thrombotic Syndrome) |
| Full-Scale Trial Secondary Outcome: Patient Reported VILLALTA Scale | 180 and 365 days | Full-Scale Trial Secondary Outcome: Patient Reported VILLALTA Scale (VILLALTA scale score ≥5 signifies clinically meaningful Post Thrombotic Syndrome) |
| Full-Scale Trial Secondary Outcome: Recurrent Venous Thromboembolism | 180 and 365 days | Full-Scale Trial Secondary Outcome: Recurrent Venous Thromboembolism |
| Full-Scale Trial Secondary Outcome: Major Bleeding | 180 and 365 days | As per International Society on Thrombosis and Haemostasis (ISTH) definition |
| Full-Scale Trial Secondary Outcome: Clinically Relevant Non-Major Bleeding | 180 and 365 days | As per ISTH definition |
| Full-Scale Trial Secondary Outcome: Overall Mortality | 180 and 365 days | Full-Scale Trial Secondary Outcome: Overall Mortality |
| Full-Scale Trial Secondary Outcome: Venous disease Specific Quality of Life | 180 and 365 days | Scoring using VEINES-QOL/Sym (The VEINES-QOL summary score (based on 25 items) estimates the impact of chronic venous disease upon QOL) |
| Full-Scale Trial Secondary Outcome: Health-Related Quality of Life | 180 and 365 days | Scoring using EuroQoL-EQ-5D-5L (EQ-5D-5L index scores range from -0.59 to 1, where 1 is the best possible health state) |
| Full-Scale Trial Secondary Outcome: Incremental Cost-Effectiveness Ratio (ICER) | 180 and 365 days | Full-Scale Trial Secondary Outcome: Incremental Cost-Effectiveness Ratio (ICER) |
Countries
Canada
Contacts
CONTACTMarc Carrier, MD,MSc,FRCPC
PRINCIPAL_INVESTIGATORMarc Carrier, MD,MSc,FRCPC
Ottawa Hospital Research Institute / Division of Hematology- The Ottawa Hospital
Outcome results
None listed