Azathioprine Versus Placebo in Pemphigus Vulgaris Treated With Prednisolone

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

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.

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

Intervention(s) in this Clinical Trial

• Drug: Azathioprine
  • It is given in a consistent dosage of 2.5 mg/kg/day throughout the study
• Drug: Prednisone
  • 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.
• Drug: Placebo
  • Placebo given in place of Azathioprine 2.5 mg/kg/day throughout the study

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Oral administration of prednisone and azathioprine throughout study
• Placebo Comparator: 2
  • Oral administration of prednisone and placebo throughout study

Primary Measures

• • Disease activity index
  • Time Frame: Throughout study; first two weeks every day, then weekly for two weeks, then monthly for eleven months
    Safety Issue?: No

Secondary Measures

• Total dose of corticosteroid
  • Time Frame: At the end of study
    Safety Issue?: No
• Occurence of any adverse event
  • Time Frame: Throughout study
    Safety Issue?: Yes
• Occurence of Grade 3 or higher treatment-related adverse event
  • Time Frame: Throughout study
    Safety Issue?: Yes
• Adverse events resulting in discontinuation and assessed by the investigators as at least possibly related to treatment
  • Time Frame: Throughout study
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 10 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Tehran University of Medical Sciences Other

Overall Clinical Trial Officials and Contacts

Cheyda Chams-Davatchi, MD Study Chair Tehran University of Medical Sciences  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00626678

Study ID Number: 87- 01-30 - 6907

ClinicalTrials.gov Identifier: NCT00626678

Health Authority: Iran: Ethics Committee