Design and Rationale of the COLT Study

Phase 3Not Yet RecruitingNCT07432529

Azienda Sanitaria Locale ASL 6, Livorno940 enrolled

Overview

Deep vein thrombosis (DVT) is a condition in which a blood clot forms in the deep veins of the leg and can lead to long-term problems such as leg pain, swelling, and reduced quality of life. Standard treatment with blood-thinning medication lowers the risk of complications, but some patients still develop long-term damage to the veins. Inflammation is thought to play an important role in these complications. This study will evaluate whether adding colchicine, an anti-inflammatory medication already used for other conditions, to standard anticoagulant therapy can improve outcomes in patients with acute DVT. Participants will be randomly assigned to receive either colchicine or a placebo, in addition to usual blood-thinning treatment, and will be followed for one year. The main goal of the study is to determine whether colchicine reduces the risk of developing long-term vein problems after DVT. The study will also assess the risk of new blood clots, vein recovery, quality of life, and the safety of colchicine treatment.

Deep vein thrombosis (DVT) of the lower limbs is a serious condition in which a blood clot forms in the deep veins of the leg. DVT can lead to long-term complications such as post-thrombotic syndrome (PTS), chronic leg swelling, pain, skin changes, and impaired quality of life. Standard treatment with anticoagulants helps prevent clot progression and reduces the risk of recurrent venous thromboembolism (VTE), but many patients still develop long-term vein damage. Inflammation is believed to play a key role in clot development, vein-wall injury, and delayed resolution of DVT. Colchicine is an anti-inflammatory medication that has been widely used in other cardiovascular and inflammatory conditions and has a favorable safety profile when used in low doses. Preliminary studies suggest colchicine may help reduce inflammation associated with DVT and promote vein recovery. The COLT-DVT study is a multicenter, randomized, double-blind, placebo-controlled clinical trial being conducted in Italy. The study will enroll approximately 940 adult patients with a first episode of acute proximal DVT of the lower limbs. Participants will be randomly assigned in a 1:1 ratio to receive either low-dose colchicine or a matching placebo, in addition to standard anticoagulant therapy. Colchicine treatment will be administered as 0.5 mg twice daily for the first month, followed by 0.5 mg once daily for the subsequent five months. Participants will be followed for a total of 12 months. The main goal of the study is to determine whether the addition of colchicine reduces the incidence of post-thrombotic syndrome one year after DVT. Secondary objectives include assessing recurrent VTE, vein reopening and valve function via duplex ultrasound, health-related quality of life using validated questionnaires, and the safety and tolerability of colchicine treatment. This study aims to provide new evidence on whether targeting inflammation in DVT can improve patient outcomes, reduce long-term complications, and potentially change standard care practices. Participants will be closely monitored for safety, and any side effects will be recorded and managed according to standard clinical practice.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥18 years at the time of screening. 2. Objectively confirmed first, symptomatic acute proximal lower-limb deep vein thrombosis (DVT), involving the popliteal vein or more proximal veins, diagnosed within the previous 48 hours. 3. Planned initiation of standard anticoagulation therapy, including: * Low-molecular-weight heparin (LMWH) bridging to vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs), * DOAC monotherapy according to local guidelines, * Fondaparinux or other guideline-recommended regimens. Note: Standard anticoagulation regimens include dose reduction of apixaban or rivaroxaban at the sixth month, as per local practice. 4. Ability and willingness to provide written informed consent and comply with all study procedures. Exclusion Criteria: Participants meeting any of the following criteria will be excluded: 1. History of prior DVT in the same limb. 2. Known contraindications to anticoagulation or anticipated inability to comply with study procedures. 3. Current use of colchicine or clinical indication requiring colchicine therapy. 4. Known hypersensitivity or allergy to colchicine. 5. Severe hepatic impairment, defined as ALT or AST \>3× upper limit of normal, or severe renal impairment (creatinine clearance \<30 mL/min). 6. Active malignancy with an estimated life expectancy \<12 months. 7. History of active or chronic gastrointestinal disease that may interfere with colchicine tolerance, including: 1. Inflammatory bowel disease (Crohn's disease or ulcerative colitis), 2. Collagenous colitis, 3. Irritable bowel syndrome, 4. Chronic or recurrent diarrhea. 8. Recent (\<30 days) or ongoing use of systemic immunosuppressive therapy, including but not limited to corticosteroids, cyclosporine, or tumor necrosis factor-alpha inhibitors. 9. Pregnancy or breastfeeding, or unwillingness to use effective contraception during the study period. 10. Concomitant use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors contraindicated with colchicine. 11. Major bleeding event within the past 30 days or assessed as high bleeding risk by the investigator. 12. Inability or unwillingness to provide informed consent or to comply with study procedures.

Outcomes

Primary Outcomes

Post-thrombotic syndrome (PTS)

To determine whether addition of low-dose colchicine to standard anticoagulation reduces the incidence of PTS at 12 months in patients with acute proximal lower-limb DVT. PTS is defined as: chronic clinical condition that occurs after DVT, presenting with symptoms such as leg pain, heaviness, cramps, pruritus, and paresthesia, and signs such as edema, skin hyperpigmentation, venous ectasia, lipodermatosclerosis, or venous ulcer, in the previously thrombosed limb, between 3 to 12 months after the acute event, and not explained by other causes \[31\]. A Villalta score \> 5 is considered diagnostic for PTS.