Clinical trial NCT04008316: Efficacy of Colchicine to Prevent Skin Relapses in Adult's IgA Vasculitis
Official title: Evaluation of Efficacy of Colchicine to Prevent Skin Relapses in Adult's IgA Vasculitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: IgA Vasculitis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, controlled, double blind, randomized clinical trial: colchicine 1mg/day versus placebo for 6 months, with a 12 months total follow-up.
Primary purpose: TREATMENT

Brief summary: Immunoglobulin A vasculitis (IgA-V), formerly called Henoch-Schönlein purpura, is an immune vasculitis. Relapses are frequent (30%) and most of the time cutaneous (90%). Cutaneous involvement in adults is more severe (haemorrhagic blister or necrotic skin lesions) and more extensive than in children. Quality of life can be significantly altered by frequent cutaneous relapses. Colchicine, historically used for gout flares, is known to be an " old " low cost drug inducing very few adverse events. This molecule inhibits polymorphonuclear cell-chemotaxis to the site of inflammation explaining colchicine clinical efficacy in diseases such as Familial Mediterranean Fever or Behçet disease. Efficacy of colchicine has also been reported in cutaneous leukocytoclastic vasculitis including IgA-V, but without clinical studies supporting this attitude.

Detailed description: Immunoglobulin A vasculitis (IgA-V), formerly called Henoch-Schönlein purpura, is an immune vasculitis. Relapses are frequent (30%) and most of the time cutaneous (90%). Cutaneous involvement in adults is more severe (haemorrhagic blister or necrotic skin lesions) and more extensive than in children. Quality of life can be significantly altered by frequent cutaneous relapses. Colchicine, historically used for gout flares, is known to be an " old " low cost drug inducing very few adverse events. It inhibits polymorphonuclear cell-chemotaxis to the site of inflammation explaining colchicine clinical efficacy in diseases such as Familial Mediterranean Fever or Behçet disease. Efficacy of colchicine has also been reported in cutaneous leukocytoclastic vasculitis including IgA-V, but without clinical studies supporting this attitude To assess efficacy of colchicine in adult's cutaneous IgA-V, the investigators conduct a prospective, controlled, double blind, randomized clinical trial, national, multicenter and multidisciplinary (internal medicine, nephrology and dermatology): colchicine 1mg/day versus placebo for 6 months, with a 12 months total follow-up. The primary objective is to evaluate efficacy of colchicine versus placebo to prevent cutaneous relapses, 6 months after inclusion, in adult patients with cutaneous IgA vasculitis alone or associated with non-severe digestive or renal involvement.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years and \< 85 years
2. IgA-V recently diagnosed (\< 20 days since skin biopsy) and defined by :

   * Histologically proven small vessels vasculitis with IgA deposits IgA Vasculitis
   * Purpura and/or involvement of at least one organ among kidney, joint, or intestinal tract

Exclusion Criteria:

1. Severe renal IgA vasculitis:

   * impaired renal function, defined as an eGFR \< 60 ml per minute per 1.73 m2 (MDRD or CKD-EPI formula)
   * proteinuria/creatinuria\> 1g/g
   * Uncontrolled blood pressure (Systolic blood pressure \> 170 mmHg, diastolic blood pressure \> 100 mmHg)
2. Severe digestive IgA vasculitis:

   * intussusception
   * massive gastrointestinal haemorrhage (requiring transfusion)
   * intestinal ischemia
   * perforation
   * abdominal pain persisting more than one day (EVA \> 5) and unresponsive to standard analgesics (level 1 or 2).
3. Prior (\< 3 months) immunosuppressive or corticosteroid therapy
4. Additional cutaneous, and/or digestive and/or chronic renal diseases.
5. HIV and B and C Chronic hepatitis
6. Pregnancy or breast feeding or women without sufficient contraception among women of childbearing
7. Known allergy or intolerance to study medication or any of its excipients (lactose, saccharose)
8. Contraindication to colchicine such as:

   * severe hepatic insufficiency
   * combination with a macrolide (except spiramycin),
   * combination with pristinamycin
9. Participation in another interventional trial
10. Patient having not signed an informed consent
11. Patient without Social Security System Insurance

Primary outcomes:
measure: the occurrence of the first cutaneous skin relapse
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Saint Louis Hospital
Study officials:
affiliation: APHP
name: Evangeline PILLEBOUT, MD
role: PRINCIPAL_INVESTIGATOR
References: