A Randomized Multicenter Study for Isolated Skin Vasculitis

JRCT ID: jRCTs051190112

Registered date:26/02/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Skin vasculitis, IgA vasculitis
• Date of first enrollment: 05/06/2020
• Target sample size: 90
• Countries of recruitment: USA,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

Experimental:Stage 1
Eligible patients will be initially randomized (1:1:1) to receive one of the 3 medications under investigation (colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint is response to treatment at month 6 (stage 1).

Experimental: Stage 2
If the patient has to discontinue the study drug within the (stage 1) 6 month study period or during the subsequent follow-up period (up to month 12) because of a lack of response (or failure), flare or side effect, he/she will be randomized again to receive one of the remaining two study drugs (stage 2, with a 1:1 randomization ratio, colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint in this second stage will again be the response to treatment at 6 months.

Outcome(s)

Primary Outcome

Efficacy of the study drugs for the treatment of skin vasculitis. [ Time Frame: Response to therapy at month 6 of the pooled study stages 1 and 2. ]
Compare response to therapies.

Secondary Outcome

1. Proportion of patients with complete response to therapy at months 3, 6 and 12
2. Proportion of patients with significant response to therapy at months 3, 6 and 12
3. Time to achieve complete or significant response
4. Time to failure for patients who achieved complete or significant response before or at month 6 but subsequently relapsed
5. Frequency of flares or new lesions per month compared to baseline
6. Physician's global assessment of response
7. Patient's global assessment of response
8. Prednisone use during study period
9. Skindex score at months 1, 3, 6, 9 and 12
10. Patient reported outcome and/or disease burden at month 1, 3, 6, 9 and 12
11. Response according to patient and disease characteristics
12. Grading of standardized photographs by blinded investigators

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patients with primary skin vasculitis, not associated with any significant extra-cutaneous involvement that would require specific immunosuppressive therapy. Eligible patients will have a diagnosis of either:
1-1. Isolated cutaneous small vessel or medium-sized vessel vasculitis or cutaneous polyarteritis nodosa.
1-2. IgA vasculitis (Henoch-Schonlein purpura), without active and/or progressing renal involvement.
2. The diagnosis of vasculitis must have been confirmed by skin biopsy prior to enrollment .
3. Patients must have active cutaneous vasculitis lasting for at least 1 month continuously and/or have had 2 or more flares over the six months preceding enrollment.
4. Patients must have active / ongoing cutaneous vasculitis lesions at the time of enrollment.
5. Patients may have a contra-indication to one of the study drug or have been treated prior to enrollment with one of the study medications but failed to respond to it or had to stop it because of an adverse event. .
6. Patients may have received systemic glucocorticoids for their cutaneous vasculitis before enrollment.
7. Participant age 18 years or greater.

Exclude criteria

1. Systemic vasculitis or more diffuse condition.
2. Known systemic and/or non-skin-isolated vasculitis.
3. Hypocomplementemic urticarial vasculitis, cryoglobulinemic vasculitis, and other known secondary skin vasculitides such as those secondary to systemic lupus erythematosus, Sjogren syndrome, another auto-immune condition, a cancer, a hematological disorder, an ongoing active infection, or an ongoing medication.
4. History of significant intolerance, allergy or serious adverse events to any of the study medications: such patients can be enrolled directly in the second stage of the study and be randomized to receive one of the two other study drugs.
5. Patients who have contra-indications to two or three of the study drugs (azathioprine, colchicine, or dapsone), or have been treated prior to enrollment with two or three of the study drugs but failed to respond to them, or had to stop two or three of them because of adverse events.
6. Deficit in glucose-6-phosphate dehydrogenase (G6PD) or history of hemolytic anemia: such patients can be enrolled directly in the second stage of the study and be randomized to receive one of the two other study drugs (azathioprine or colchicine).
7. Low or absent thiopurine methyltransferase (TPMT) activity: Patients known to have low or absent TPMT can be enrolled directly in the second stage of the study and be randomized to receive one of the two other study drugs (dapsone or colchicine).
8. Evidence of significant hepatic insufficiency or liver function tests > 2 times the upper limit of normal.
9. Evidence of significant renal insufficiency or creatinine clearance < 60 mL/min.
10. Evidence of significant or symptomatic anemia or Hb < 10 g/dL.
11. Comorbid condition that has moderate or high likelihood of requiring intermittent courses of prednisone within the study period, according to the investigator (e.g. chronic obstructive pulmonary disease (COPD), unstable or severe asthma).
12. Active cancer or history of malignancy within the previous 5 years (patient in remission of a cancer >5 years, or with non-metastatic prostate cancer or treated basal or squamous cell carcinoma of the skin can be enrolled).
13. Active uncontrolled or serious infection that may compromise or contra-indicate the use of the study medications.
14. Patient unable to consent.
15. Pregnant or lactating women.

Related Information

• Primary Sponsor: Kawakami Tamihiro
• Secondary ID(s): NCT02939573