Osteoarthritis, Hip, Osteoarthritis, Knee
Conditions
Keywords
Colchicine, Knee replacement, Hip replacement
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
Interventions
DRUGColchicine
Colchicine 0.5mg tablets once a day for 3 to 4.5 years
DRUGPlacebo
Placebo tablets once a day for 3 to 4.5 years
Sponsors
ZonMw: The Netherlands Organisation for Health Research and Development
RSMK
Tiofarma
Dutch Arthritis Foundation Reuma Nederland
Sint Maartenskliniek
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* clinical diagnosis of knee or hip OA * 45 ≤ 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
Exclusion criteria
* 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 * Pregnant or breastfeeding female * Fertile female participants not taking sufficient anti-conception * Male participants unwilling to use effective contraception during the study to prevent pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Number of participants using pain medication during the study registered per drug type (e.g. paracetamol, NSAIDs, opioids) | 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 | — |
| Onset of new cardiovascular events, defined as myocardial infarction, peripheral artery disease, ischemia-driven coronary revascularization, ischemic stroke, or cardiovascular death | 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 | — |
| Direct and indirect costs related to treatment and disease burden due osteoarthritis | 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 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 | The 11-point NRS ranges from '0' (no pain) to '10' (worst pain imaginable) |
| 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 | 5 items are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). Higher scores indicate more pain |
| 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 | 17 items are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). Higher scores indicate more functional limitations |
| 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 quality of life as assessed by EQ-5D-5L (European Quality of Life 5 Dimensions) | 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 EQ-5D-5L comprises 5 dimensions with each dimension having 5 response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), unable to/extreme problems (5). EQ-5D-5L health states can be represented by a single summary number (index value) (range -0.624 to 1.000). Higher scores equals better quality of life |
| Number of participants with clinical or radiological onset of OA in new joint group other than present at baseline over the trial period | 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 | — |
| Time to clinical or radiological onset of OA in new joint group other than present at baseline over the trial period | 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 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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 | Adverse events are defined as any untoward medical occurrence in a subject to whom a medicinal product is administered, and which does not necessarily have a causal relationship with this treatment. Serious adverse event is any untoward medical occurrence in a patient or trial subject that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect |
| 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 | Adverse events are defined as any untoward medical occurrence in a subject to whom a medicinal product is administered, and which does not necessarily have a causal relationship with this treatment. Serious adverse event is any untoward medical occurrence in a patient or trial subject that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect |
Countries
Netherlands
Contacts
Primary ContactTim Massa
Outcome results
None listed