Trial of Colchicine Versus Prednisone for the Treatment of Acute CPPD Arthritis

Study Overview
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Brief Summary
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Chondrocalcinosis, recently renamed the calcium pyrophosphate deposition (CPPD) disease, is a very frequent affection of the elderly and causes very painful arthritis. International recommendations for the treatment of patients suffering from CPPD are based upon rare studies, not randomized, with small samples, and thus very weak scientific evidence. The treatment of CPPD arthritis is extrapolated from the experience of gout treatment, another crystal deposition disease. Among recommended treatments, colchicine and oral steroids are recommended as first-line treatments, while NSAIDs are used with caution in elderly populations of patients. Colchicine utilization is not risk-free, in particular with old patients and patients with renal impairment. Drug interactions of colchicine can have serious consequences, especially in a polymedicated old patient's population. Oral steroids are an interesting alternative in this indication with a potential of being better tolerated, but comparative efficacy with colchicine needs to be studied. From a broader point of view, colchicine and oral steroids have never been compared in any crystal related arthritis. This is the first large randomized controlled trial for CPPD acute arthritis.

Detailed Description
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Chondrocalcinosis, recently renamed the calcium pyrophosphate deposition (CPPD) disease, is a very frequent affection of the elderly and causes very painful arthritis. International recommendations for the treatment of patients suffering from CPPD are based upon rare studies, not randomized, with small samples, and thus very weak scientific evidence. Some factors are known to trigger CPPD arthritis (trauma, surgery, infection, hospitalization). Prevalence increases with age, and case series estimate the presence of chondrocalcinosis in over 20% of 80 plus years population. International recommendations for the treatment of patients suffering from CPPD are based upon rare studies, not randomized, with small samples, and thus very weak scientific evidence. The treatment of CPPD arthritis is extrapolated from the experience of gout treatment, another crystal deposition disease (this one related to monosodium urate crystals that deposit after long-standing hyperuricemia. Among recommended treatments, colchicine and oral steroids are recommended as first-line treatments, while NSAIDs are used with caution in elderly populations of patients. Colchicine utilization is not risk-free, in particular with old patients and patients with renal impairment. Drug interactions of colchicine can have serious consequences, especially in a polymedicated old patient's population. Oral steroids offer an interesting alternative with the potential of being better tolerated. However, even oral steroids are recommended, their efficacy in CPPD arthritis isn't demonstrated. Interesting comparative results with NSAIDs were shown for the treatment of gout flares. These results may not be fully extrapolated to CPPD which holds differences with gout. In addition, oral steroids were not compared to colchicine which is the benchmark treatment in many countries for CPPD. The aim of this study is to compare the efficacy of colchicine and oral steroids for the treatment of CPPD acute arthritis and compare their tolerance profile. It is the first large randomized controlled trial comparing two treatments of CPPD acute arthritis.

Official Title
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Colchicine or Prednisone for the Treatment of Acute Calcium Pyrophosphate Deposition (CPPD) Arthritis: Open-label, Randomized, Multicenter, Equivalence Trial of Efficacy and Safety

Conditions
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Chondrocalcinosis

Intervention / Treatment
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* Drug: Colchicine opocalcium 1mg
* Drug: Prednisone : Cortancyl 20mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged 65 and older Patient with mono/polyarticular CPPD acute arthritis Hospitalized patient (without infectious syndrome considered insufficiently controlled by the clinicians and diabetic decompensation) Diagnosis confirmed : By the evidence of CPP crystals on synovial fluid examination. By the existence of a typical clinical arthritis (joint pain, erythema, swelling, maximal intensity in less than 24h) AND presence of chondrocalcinosis signs in knee, wrists, or pubic symphysis on plain X-rays or crowned tooth in cervical rachis scan. Pain VAS ≥ 40/100 at the enrollment Duration of symptoms evolution for less than 36h. No prior intake of oral steroids, colchicine or NSAIDs for this acute arthritis. Signed patient's consent. Affiliation to a social security scheme. Exclusion Criteria: Contraindication to colchicine (creatinine clearance below 30ml/min, severe hepatic dysfunction, macrolide or ongoing pristinamycin or macrolid treatment, …) or corticoids utilization (uncontrolled diabetes, uncontrolled progressive infection, uncontrolled arterial hypertension…) Severe cognitive disorders that does not allow patient to evaluate his pain. Patient under guardianship, curatorship Patient receiving morphinic analgesia. Gout history or presence of monosodium urate crystals at the examination of the synovial fluid.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colchicine<br>Patients assigned to this group will receive the Colchicine opocalcium 1mg treatment. | Drug: Colchicine opocalcium 1mg<br>* International non-proprietary name: Colchicine Molecule owner: Mayoly-Spindler Laboratory, 1mg scored tablet for oral administration, authorized 03/02/1995. Composition : Active principle : Crystallized colchicine Excipients: Erythrosine aluminium lake, lactose, saccharose, magnesium stearate and povidone.<br>* Other names: Mayoly-Spindler laboratory;|
| Experimental: Prednisone (corticoids)<br>Patients assigned to this group will receive Prednisone : Cortancyl 20mg. | Drug: Prednisone : Cortancyl 20mg<br>* International non-proprietary name: Prednisone Molecule owner : SANOFI AVENTIS France 20 mg scored tablet for oral administration, authorized since 02/05/1990, generic drug available. Composition : Active principle : Prednisone Excipients: Maize starch, lactose, talc, magnesium stearate.<br>* Other names: Sanofi Aventis France;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the pain VAS at 24 hours | Evolution of the pain Visual Analog Scale (VAS), between baseline and 24 hours after the first treatment administration, without any recourse to other anti-inflammatory treatments. | From the first treatment administration to 24 hours after. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with at least one adverse event within 48 hours | Proportion of patients with at least one adverse event within 48 hours following the first drug intake (diarrhea, abdominal pain, nausea, vomiting, a 50% fasting blood glucose increase, excitability, sleep disorders, high blood pressure apparition [above 140/90mmHg], change in creatinine clearance) | 48 hours following the first administration | 
| Change from baseline of biological inflammatory syndrome at 48 hours | C Reactive Protein change from baseline 48 hours after the first treatment intake. | From the first treatment administration to 48 hours after. | 
| Number of joints affected and their localizations | Number of affected articulations and their localization before the first intake, after 24 hours and after 48 hours. | Before, 24 hours and 48 hours after the first administration | 
| Need of emergency morphinic treatment | Proportion of patients requiring analgesia with morphine within the first 24 hours. | 24 hours after the first administration | 
| Analgesic consumption | Proportion of patients requiring additional analgesics between the 24th and 48th hour following the 1st intake. | From 24 hours to 48 hours after the first treatment administration | 
| Proportion of patients with an efficacy response of at least 50% | Proportion of patients with at least a 50% decrease in pain VAS at 24 and 48 hours after the first intake. | 24 hours and 48 hours after the first administration. | 
| Proportion of patients with an efficacy response of at least 20% | Proportion of patients with at least a 20% decrease in pain VAS at 8, 12 and 24 hours after the first administration. | 8, 12 and 24 hours after the first administration. | 
| Complete crisis resolution within 7 days | Proportion of patient with a complete resolution of the arthritis within the 7 days after 1st intake (defined by a ≤3/10 VAS score) | 7 days after 1st administration | 
| Initial crisis resolution delay | Delay to the complete resolution of the arthritis from the first drug intake | 7 days after 1st administration | 
| Absence of crisis recidivism within 7 days | Relapse rate within the 7 days following the 1st intake (defined by the recurrence of pain with a >3/10 VAS score) | Within the 7 days following the 1st administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colchicine, Corticoids, Prednisone, CPPD, Calcium Pyrophosphate Deposition Disease