Design and Rationale of the COLT Study (COLT)

Design and Rationale of the COLT Study: a Multicentre, Randomised, Double-blind, Placebo-controlled Trial of COLchicine as Adjunctive Therapy to Standard Anticoagulation in Acute Proximal Deep Vein Thrombosis of the Lower Limbs

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Venous Insufficiency; Venous Thromboembolism (VTE); Post-thrombotic Syndrome; Venous Thrombosis Deep (Limbs)
• Intervention / Treatment: Drug: Colchicine 0.5 MG Oral Tablet; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 940
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nicola Mumoli NM Dr; Phone Number: +39 0331699111; Email: nimumoli@tiscali.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Colchicine + Standard Anticoagulation; Participants in this arm will receive low-dose colchicine in addition to standard anticoagulant therapy for deep vein thrombosis. Colchicine 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 monitored for safety, efficacy, and outcomes including post-thrombotic syndrome, recurrent venous thromboembolism, vein recanalization, and quality of life over a 12-month follow-up period.	Drug: Colchicine 0.5 MG Oral Tablet; Low-dose colchicine added to standard anticoagulant therapy for acute proximal deep vein thrombosis. Colchicine is administered 0.5 mg twice daily for the first month, then 0.5 mg once daily for the next five months. Participants are monitored for post-thrombotic syndrome, recurrent venous thromboembolism, vein recanalization, quality of life, and safety over 12 months.
Placebo Comparator: Arm 2 - Placebo + Standard Anticoagulation; Participants in this arm will receive a matching placebo in addition to standard anticoagulant therapy for deep vein thrombosis. Placebo will be administered following the same schedule as colchicine (0.5 mg twice daily for one month, then 0.5 mg once daily for five months). Participants will be monitored for the same outcomes and safety measures over a 12-month follow-up period.	Drug: Placebo; Matching placebo administered alongside standard anticoagulant therapy on the same schedule as colchicine. Participants are monitored for the same outcomes and safety measures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From the start of treatment to the 12-month follow-up visit
Recurrent venous thromboembolism.	To evaluate the effect of low-dose colchicine added to standard anticoagulation on the incidence of recurrent venous thromboembolism (VTE), defined as objectively confirmed recurrent DVT and/or pulmonary embolism (PE), within 12 months of the index event.	From the start of treatment to the 12-month follow-up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal evaluation of PTS severity	Subgroup analysis evaluating differences in efficacy of low-dose colchicine added to standard anticoagulation in mild (5-9) to moderate (10-14) to severe PTS (> 15).	From the start of treatment to the 12-month follow-up visit
Venous healing and function on imaging	To assess the effect of colchicine on venous recanalization and valvular competence at 3 months using duplex ultrasound, including: vein compressibility,; residual vein obstruction,; presence of venous reflux.	From the start of treatment to the 12-month follow-up visit
Change From Baseline in Health-Related Quality of Life (HRQOL) as Measured by the VEINES-QOL/Sym Questionnaire	Change from baseline in health-related quality of life as measured by the Venous Insufficiency Epidemiological and Economic Study - Quality of Life/Symptoms (VEINES-QOL/Sym) questionnaire. The VEINES-QOL score ranges from 0 to 100, with higher scores indicating better quality of life. The VEINES-Sym score ranges from 0 to 100, with higher scores indicating fewer symptoms.	From the start of treatment to the 12-month follow-up visit
Adverse event and treatment discontinuation	To determine the 12-months safety profile of colchicine in this population (major and clinically relevant non-major bleeding, defined by ISTH definitions, gastrointestinal adverse events, neutropenia).	From the start of treatment to the 12-month follow-up visit
Adherence and persistence to colchicine therapy	To evaluate adherence and persistence to colchicine treatment and to explore their association with clinical outcomes, including PTS severity and recurrent VTE.	From the start of treatment to the 12-month follow-up visit

Collaborators and Investigators

• Sponsor: Azienda Sanitaria Locale ASL 6, Livorno

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 14, 2026
• First Submitted That Met QC Criteria: February 21, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 21, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Randomized controlled trial; Deep vein thrombosis; Venous thromboembolism; Colchicine; Post-thrombotic syndrome; Anticoagulation therapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Embolism and Thrombosis; Thromboembolism; Thrombosis; Pathological Conditions, Signs and Symptoms; Venous Thrombosis; Inflammation; Postthrombotic Syndrome; Venous Thromboembolism; Venous Insufficiency; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Alkaloids; Colchicine; Tablets
• Other Study ID Numbers: COLT123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in this study, including the analyzable dataset and data dictionary, will be made available.
• IPD Sharing Access Criteria: Data will be available upon reasonable request to the corresponding author, following approval of a research proposal and in compliance with institutional and ethical regulations. Data will be shared in a de-identified format to protect participant confidentiality.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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