Efficacy of Colchicine to Prevent Skin Relapses in Adult's IgA Vasculitis (COLCHIVAS)

Evaluation of Efficacy of Colchicine to Prevent Skin Relapses in Adult's IgA Vasculitis

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.

Study Overview

• Status: Recruiting
• Conditions: IgA Vasculitis
• Intervention / Treatment: Drug: Colchicine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 264
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Evangeline PILLEBOUT, MD; Phone Number: +33 1 42 49 96 05; Email: evangeline.pillebout@aphp.fr
• Study Contact Backup: Name: Alexandra AUDMARD-VERGER, MD; Phone Number: +33 2 31 06 45 79; Email: alexandra.audemard-verger@chu-caen.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Saint Louis Hospital
    • Contact: Alexandra AUDMARD-VERGER, MD; Phone Number: +33 2 31 06 45 79; Email: alexandra.audemard-verger@chu-caen.fr
    • Contact: Evangeline PILLEBOUT, MD; Phone Number: +33 1 42 49 96 053; Email: evangeline.pillebout@aphp.fr
    • Principal Investigator: Alexandra AUDMARD-VERGER, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: colchicine 1mg/day; Colchicine per os: 1 tablet (1mg) / day during 6 months	Drug: Colchicine; colchicine 1mg/day
Placebo Comparator: placebo; placebo 1 tablet / day during 6 months	Drug: Colchicine; colchicine 1mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the occurrence of the first cutaneous skin relapse	Cutaneous skin relapse is defined by reappearance of palpable purpura with lower limb predominance and not related to thrombocytopenia.	6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Evangeline PILLEBOUT, MD, APHP

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Anticipated): November 12, 2022
• Study Completion (Anticipated): May 12, 2023

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Hemostatic Disorders; Hypersensitivity; Blood Coagulation Disorders; Skin Manifestations; Immune Complex Diseases; Purpura; Vasculitis; Purpura, Schoenlein-Henoch; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: P170910J; 2018-002114-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No