Azathioprine Versus Placebo in Pemphigus Vulgaris Treated With Prednisolone

Study Overview
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Brief Summary
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Description: Pemphigus vulgaris is an autoimmune, chronic and recurrent blistering disease with unknown etiology that affects mucosa and skin of patients with significant morbidity and mortality. The treatment back-bone is based on prednisolone administration. There are controversies on the opportunity of adding immunosuppressive drugs. For some, they are just corticosteroid sparing drugs. For others, they are disease modifying drugs. The purpose of this trial is to compare efficacy and safety of azathioprine vs. placebo in new cases of pemphigus vulgaris treated with prednisolone.

Detailed Description
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The purpose of this trial is to compare efficacy and safety of azathioprine vs. placebo in new cases of pemphigus vulgaris treated with prednisolone. Official Title: Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Azathioprine in New Cases of Pemphigus Vulgaris Receiving Prednisolone Randomized Double Blind Controlled Trial of Azathioprine versus Placebo in new cases of Pemphigus Vulgaris treated with Prednisolone Study Type: Interventional Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Controlled, Parallel Assignment, Safety/Efficacy Study Condition Intervention Phase Pemphigus Vulgaris Drug: Azathioprine Drug: Prednisolone Other: Placebo Phase II

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Adjuvant Azathioprine Therapy in New Cases of Pemphigus Vulgaris Receiving Prednisone

Conditions
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Pemphigus Vulgaris

Intervention / Treatment
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* Drug: Azathioprine
* Drug: Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lesions clinically consistent with pemphigus vulgaris Diagnosis confirmed by histology in terms of acantholysis within past month Positive DIF Exclusion Criteria: Any nursing or pregnant woman Any history of chronic diseases including liver disease, Chronic Renal Failure, Chronic Heart Failure or Ischemic Heart Disease Present diagnosis of hepatitis confirmed by serology or elevated hepatic enzymes; Clinically significant concurrent medical disease or laboratory abnormalities evidenced by one or more of the following: Hepatobiliary AST or ALT ≥ 1.5 × upper limit of normal (ULN);alkaline phosphatase ≥ 1.5 × ULN; or, total bilirubin > 90% of the ULN; Renal serum creatinine > 1.5 mg/dL; or, significant proteinuria > 2+ on urinary dip test; Hematologic hemoglobin < 11 mg/dL; leukocytes < 3.5 × 109/L; neutrophils < 1.5 × 109/L; or, platelets < 100 × 109/L; Presence of anemia, leukopenia or thrombocytopenia Any sign of patient's non-compliance Known hypersensitivity to study drugs, prednisone or azathioprine Participating in another clinical trial at the time of screening and enrollment

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Oral administration of prednisone and azathioprine throughout study | Drug: Azathioprine<br>* It is given in a consistent dosage of 2.5 mg/kg/day throughout the study<br>* Other names: Imuran;Drug: Prednisone<br>* Oral corticosteroid initiated at 2 mg/kg/day dosage. Dosage may be tapered primarily by 1/3 total dosage if no new blister, then 5 mg every three days to reach the daily dosage of 30 mg then tapered by 1.25 mg every week to reach daily dosage of 20 mg/day, then tapered by 1.25 mg every two weeks to reach daily dosage of 10 mg, then tapered by 1.25 mg monthly to reach daily dosage of 7.5 mg and continue this dosage for six months then tapered to 5 mg/day if no new lesions are observed as determined by clinical assessment of the investigator.<br>* Other names: Orasone®;|
| Placebo Comparator: 2<br>Oral administration of prednisone and placebo throughout study | Drug: Prednisone<br>* Oral corticosteroid initiated at 2 mg/kg/day dosage. Dosage may be tapered primarily by 1/3 total dosage if no new blister, then 5 mg every three days to reach the daily dosage of 30 mg then tapered by 1.25 mg every week to reach daily dosage of 20 mg/day, then tapered by 1.25 mg every two weeks to reach daily dosage of 10 mg, then tapered by 1.25 mg monthly to reach daily dosage of 7.5 mg and continue this dosage for six months then tapered to 5 mg/day if no new lesions are observed as determined by clinical assessment of the investigator.<br>* Other names: Orasone®;Drug: Placebo<br>* Placebo given in place of Azathioprine 2.5 mg/kg/day throughout the study<br>* Other names: Vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Disease activity index |  | Throughout study; first two weeks every day, then weekly for two weeks, then monthly for eleven months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total dose of corticosteroid |  | At the end of study | 
| Occurence of any adverse event |  | Throughout study | 
| Occurence of Grade 3 or higher treatment-related adverse event |  | Throughout study | 
| Adverse events resulting in discontinuation and assessed by the investigators as at least possibly related to treatment |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pemphigus Vulgaris, Azathioprine, Prednisone