Azathioprine Versus Placebo in Pemphigus Vulgaris Treated With Prednisolone

Sponsor

Tehran University of Medical Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT00626678

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pemphigus Vulgaris	Drug: Azathioprine Drug: Prednisone Drug: Placebo	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Sep 1, 2008

Actual Study Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Oral administration of prednisone and azathioprine throughout study	Drug: Azathioprine It is given in a consistent dosage of 2.5 mg/kg/day throughout the study Other Names: Imuran 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. Other Names: Meticorten ® Deltasone® Orasone®
Placebo Comparator: 2 Oral administration of prednisone and placebo throughout 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. Other Names: Meticorten ® Deltasone® Orasone® Drug: Placebo Placebo given in place of Azathioprine 2.5 mg/kg/day throughout the study Other Names: Vehicle

Arm

Intervention/Treatment

Experimental: 1

Oral administration of prednisone and azathioprine throughout study

Drug: Azathioprine

It is given in a consistent dosage of 2.5 mg/kg/day throughout the study

Other Names:

Imuran

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.

Other Names:

Meticorten ®

Deltasone®

Orasone®

Placebo Comparator: 2

Oral administration of prednisone and placebo throughout study

Drug: Prednisone

Other Names:

Meticorten ®

Deltasone®

Orasone®

Drug: Placebo

Placebo given in place of Azathioprine 2.5 mg/kg/day throughout the study

Other Names:

Vehicle

Outcome Measures

Primary Outcome Measures

• Disease activity index [Throughout study; first two weeks every day, then weekly for two weeks, then monthly for eleven months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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