Clinical trial NCT03128905: Trial of Colchicine Versus Prednisone for the Treatment of Acute CPPD Arthritis
Official title: Colchicine or Prednisone for the Treatment of Acute Calcium Pyrophosphate Deposition (CPPD) Arthritis: Open-label, Randomized, Multicenter, Equivalence Trial of Efficacy and Safety
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chondrocalcinosis
Keywords: Colchicine
Corticoids
Prednisone
CPPD
Calcium Pyrophosphate Deposition Disease
Lead sponsor: Lille Catholic University
Sponsor class: OTHER
Collaborators: name: University Hospital, Lille
name: Hopital Lariboisière
name: Bichat Hospital
name: Valenciennes Hospital Centre
name: Armentières Hospital Centre
name: Dunkerque Hospital Centre
First posted: 2017-04-25
Enrollment: 111
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in the pain VAS at 24 hours
timeFrame: From the first treatment administration to 24 hours after.
Secondary outcomes:
measure: Proportion of patients with at least one adverse event within 48 hours
timeFrame: 48 hours following the first administration
measure: Change from baseline of biological inflammatory syndrome at 48 hours
timeFrame: From the first treatment administration to 48 hours after.
measure: Number of joints affected and their localizations
timeFrame: Before, 24 hours and 48 hours after the first administration
measure: Need of emergency morphinic treatment
timeFrame: 24 hours after the first administration
measure: Analgesic consumption
timeFrame: From 24 hours to 48 hours after the first treatment administration
measure: Proportion of patients with an efficacy response of at least 50%
timeFrame: 24 hours and 48 hours after the first administration.
measure: Proportion of patients with an efficacy response of at least 20%
timeFrame: 8, 12 and 24 hours after the first administration.
measure: Complete crisis resolution within 7 days
timeFrame: 7 days after 1st administration
measure: Initial crisis resolution delay
timeFrame: 7 days after 1st administration
measure: Absence of crisis recidivism within 7 days
timeFrame: Within the 7 days following the 1st administration
Other outcomes:
Locations:
city: Valenciennes
country: France
facility: CH Valenciennes
state: Hauts-de-France
city: Paris
country: France
facility: Hôpital Bichat
state: Ile De France
city: Lille
country: France
facility: CHRU Lille
state: Nord Pas De Calais
city: Lille
country: France
facility: Lille Catholic Hospital
state: Nord Pas De Calais
city: Armentières
country: France
facility: Dr Nicolas SEGAUD
city: Dunkerque
country: France
facility: Dr Rémi LEROY
city: Paris
country: France
facility: Hôpital de Lariboisière
state: Île De France
Study officials:
affiliation: Lille Catholic University
name: Eric Houvenagel, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Lille Catholic University
name: Tristan Pascart, Dr
role: STUDY_CHAIR
References: