The Effect of ColcHicine on the Incidence of Knee or Hip Replacements

NCT06578182 | Recruiting Phase 3

• 3 other identifiers: SMaartenskliniek101402622100122024-511359-16-00
• Study Type: interventional
• Target: 1,410
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the effect of treatment with colchicine 0.5mg once daily as compared to placebo in patients with knee or hip osteoarthritis on the incidence of first occurrence of knee or hip replacement. The main question it aims to answer is: Does colchicine lower the number of knee or hip replacements in participants with osteoarthritis? Researchers will compare colchicine to a placebo (a look-alike substance that contains no drug) to see if colchicine works to treat osteoarthritis. Participants will:

• take colchicine every day for 3 tot 4.5 years
• visit the clinic every year for check-up and tests such as blood samples and x-rays
• fill in questionnaires every 3 months

Conditions

Osteoarthritis, Knee; Osteoarthritis, Hip

Keywords

Colchicine; Knee replacement; Hip replacement

Outcome Measures

Primary Outcomes (1)

• Time to first knee or hip replacement

  From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

Secondary Outcomes (11)

• Course of pain as assessed by NRS (numeric rating scale)

  From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

• Course of pain as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index)

  From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

• Course of physical function as assessed by WOMAC (Western Ontario and McMaster Universities Arthritis Index)

  From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

• Course of joint space narrowing on X-ray

  From baseline until the date of first documented knee or hip replacement or study end, whichever comes first, assessed up to 4.5 years

• Course of low-grade inflammation as assessed by hs-CRP

  At enrolment, at baseline, 1 year thereafter, and at study completion (approximately 4.5 years)

Other Outcomes (3)

• The number of (serious) adverse events

  From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

• The number of withdrawals due to (serious) adverse events

  From randomization until the date of first documented knee or hip replacement, date of death, date of lost to follow-up, or study end-date, whichever comes first, assessed up to 4.5 years

• Changes in laboratory data (i.e. serum creatinine, estimated glomerular filtration rate, and alanine transferase)

  At enrolment, at baseline, 1 year thereafter, and at study completion (approximately 4.5 years)

Study Arms (2)

Colchicine

EXPERIMENTAL

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Colchicine DRUG

Colchicine 0.5mg tablets once a day for 3 to 4.5 years

Colchicine

Placebo DRUG

Placebo tablets once a day for 3 to 4.5 years

Placebo

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical diagnosis of knee or hip OA
• ≤ age ≤ 80 (upper age limit is similar to that in the LoDoCo2 trial and takes in consideration the lower number of joint replacements in people older than 80 years)
• documented radiographic changes typical for advanced knee/hip OA (Kellgren \& Lawrence score ≥ 2), or at least 2-year history of complaints due to OA in the hip and/or knee

You may not qualify if:

• On a waiting list for primary joint replacement surgery of the hip or knee, irrespective of cause
• Any absolute contraindication for knee or hip replacement in the future
• More than one previous hip or knee replacements
• Other known medical disease that may affect joints
• Known generalized pain syndromes such as fibromyalgia
• Renal impairment as evidenced by serum creatinine \>150µmol/l or estimated glomerular filtration rate (eGFR) \<50mL/min/1.73m2
• Liver function impairment as evidenced by serum alanine transferase (ALAT) \> 3 ULN (upper limit of normal)
• Blood dyscrasia
• High frailty (clinical frailty scale ≥ 7) or predicted life expectancy \< 5 years
• Peripheral neuritis, myositis or marked myo-sensitivity to statins
• Current use of colchicine for another indication
• Intolerance to colchicine
• use of macrolide antibiotics (i.e. clarithromycin, erythromycin, azithromycin), antimycotics (i.e. ketoconazole, itraconazole and voriconazole), protease inhibitors \& anti-retroviral drugs (i.e. ritonavir, lopinavir, tipranavir, atazanavir, darunavir, indinavir, saquinavir, and cobicistat), anti-arrhythmic drugs (i.e. verapamil, diltiazem), or immunosuppressant (i.e. cyclosporine)
• Current enrollment in another trial
• Incapacitated patients

Sponsors & Collaborators

• Sint Maartenskliniek: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• RSMK: collaborator
• Tiofarma: collaborator
• Dutch Arthritis Foundation Reuma Nederland: collaborator

Study Sites (1)

Sint Maartenskliniek

Nijmegen, Netherlands

RECRUITING

Related Publications (1)

• Heijman MWJ, van den Ende CHM, Cornel JH, Smolders JMH, Schers HJ, Kievit W, Koeter S, van den Bemt BJF, Popa CD. Design of a randomised, placebo-controlled, double-blind multicentre study assessing the effect of colchicine on the incidence of knee or hip replacements in symptomatic knee or hip osteoarthritis: the ECHO trial. BMJ Open. 2025 Apr 14;15(4):e098096. doi: 10.1136/bmjopen-2024-098096.

  PMID: 40228852 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis, Hip

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Central Study Contacts

Tim Massa

CONTACT

+31633036353; t.massa@maartenskliniek.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: August 29, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: February 20, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)