Efficacy of Dapsone as a Steroid Sparing Agent in Pemphigus Vulgaris - Full Text View

Sponsored by:	Jacobus Pharmaceutical
Information provided by:	Jacobus Pharmaceutical
ClinicalTrials.gov Identifier:	NCT00429533

Purpose

The purpose of this 12-month study was to determine the efficacy of dapsone as a glucocorticoid-sparing agent in maintenance phase pemphigus vulgaris.

Condition	Intervention	Phase
Pemphigus Vulgaris	Drug: Dapsone	Phase II

MedlinePlus related topics: Pemphigus

Drug Information available for: Dapsone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	A Prospective Randomized Placebo-Controlled Clinical Trial of Dapsone as a Glucocorticoid-Sparing Agent in Maintenance Phase Pemphigus Vulgaris

Further study details as provided by Jacobus Pharmaceutical:

Primary Outcome Measures:

The ability of patients to taper to ≤7.5mg/day within one year of reaching the maximum dosage of the study drug.

Secondary Outcome Measures:

Steroid dosage reduced by more than 25% within 4 months after completing the upward titration of the study drug.

Estimated Enrollment:	48
Study Start Date:	November 1996
Estimated Study Completion Date:	February 2004

Detailed Description:

Patients were entered into the trial on steroids in combination with cytotoxic agents as needed. The steroid dose was the lowest dose at which the patient’s disease was controlled before the last flare (see eligibility criteria). The patients were randomized to receive either Dapsone or placebo.

Treatment was to be started at a dose of 50 mg and increased by 25 mg increments each week once the hemoglobin was shown not to have dropped by more than 2 gm/dl. The target dose was 150 mg and patients who did not respond could be advanced to 200 mg daily. After beginning treatment, a standardized steroid taper was commenced. A standardized steroid taper was suggested with tapering by 10 mg/wk for doses above 40 mg/day or more slowly if warranted. A slower taper thereafter or an every other day dosing schedule would be elected according to the individual investigator’s preference.

Flares were treated by increasing the dose of steroids - in the case of a mild flare to the last dose preceding the flare, in the case of a moderate flare by 20 mg/day and in the case of a severe flare by 40 mg/day. Tapering was to be resumed once the disease had stabilized. Disease activity was assessed by a simple scoring system for skin, mucosa, and sites involved. Laboratory assessments initially weekly became monthly once the study medication dosage was stabilized.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologic evidence compatible with pemphigus vulgaris and direct immunofluorescence evidence of pemphigus vulgaris.
Chronic disease that has been controlled with steroids and/or cytotoxics, e.g. maintenance phase.
On prednisone 15 or more mg/day to around 40 mg/day or on prednisone 15 or more mg every other day (qod) to around 40 mg qod.
Failure to taper steroids below a range of 15 mg/day to around 40 mg/day or 15 mg/qod to around 40 qod without flaring the disease.
The steroid dosage at which the most recent flare occurred should not be less than 85% of the last (within 30 days) dosage which controlled the disease, i.e. 85% of the baseline steroid dosage. This is to ensure that patients will not have had a recent acute flare at the time of entry into the study, and be in the rapid steroid taper portion of their disease after such a flare.
Two baseline steroid dosages as determined by prior flares. It is common that patients will be repetitively unable to taper below a certain baseline steroid dose without experiencing a mild flare of their disease. This baseline dose will be determined on two occasions during attempted tapers, and the baseline number then averaged to determine the dose of steroid the patient is on at the time of entry into the study.
No pulse steroids, pulse cyclosphosphamide, or plasmapheresis within two months of beginning the protocol. This will exclude patients who had recent acute flares of their disease and may be on the rapid steroid taper portion of their disease. The patient must be in maintenance phase, as defined in the criteria listed in e.
Patient understands the procedures and agrees to participate in the study program by giving written informed consent.

Exclusion Criteria:

Patients able to taper steroids without recurrence of disease.
Patients with early, severe disease that have not responded to high doses of prednisone, cytotoxics, plasmapheresis, or other modalities.
Contraindications to the use of Dapsone, including severe anemia or G6PD deficiency.
Patient has behavioral problems that might interfere with compliance.
Pregnancy or breast-feeding.
Younger than 18 or older than 80 years of age. Since PV is rare in patients younger than 18, it was decided to exclude this potentially different population. It is unlikely that this will exclude many patients. Dapsone induces a hemolytic anemia, which would be a particular problem for patients over age 80, who are more likely to have ischemic heart disease or other atherosclerotic vascular disease.
History of allergy to dapsone.
Ischemic heart disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429533

Locations

United States, Illinois
Northwestern University Medical Center
Chicago, Illinois, United States, 60611-3010
Rush-Presbyterian-St. Luke's Medical Center
Chicago, Illinois, United States, 60612
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, New Jersey
Cooper Hospital/University Medical Center
Camden, New Jersey, United States, 08103
United States, New York
The New York VA Medical Center, New York University
New York, New York, United States, 10010
United States, Ohio
Case Western Reserve University School of Medicine
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas
Dallas, Texas, United States, 75235

Sponsors and Collaborators

Jacobus Pharmaceutical

Investigators

Study Chair:	Victoria P. Werth, MD	University of Pennsylvania
Principal Investigator:	Victoria P. Werth, MD	University of Pennsylvania
Principal Investigator:	Diana Chen, MD	Northwestern University
Principal Investigator:	Warren R Heymann, MD	Cooper Hospital/University Medical Center
Principal Investigator:	Neil Korman, MD	Case Western Reserve University School of Medicine
Principal Investigator:	Amit Pandya, MD	University of Texas
Principal Investigator:	M J Rico, MD	The New York VA Medical Center - New York University
Principal Investigator:	Michael D Tharp, MD	Rush University Medical Center

More Information

No publications provided by Jacobus Pharmaceutical

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Werth VP, Fivenson D, Pandya AG, Chen D, Rico MJ, Albrecht J, Jacobus D. Multicenter randomized, double-blind, placebo-controlled, clinical trial of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris. Arch Dermatol. 2008 Jan;144(1):25-32.

Study ID Numbers:	51,988
Study First Received:	January 29, 2007
Last Updated:	February 1, 2007
ClinicalTrials.gov Identifier:	NCT00429533 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Folic Acid
Anti-Bacterial Agents
Antimalarials
Pemphigus Vulgaris
Autoimmune Diseases
Skin Diseases, Vesiculobullous

Skin Diseases
Dapsone
Folic Acid Antagonists
Glucocorticoids
Pemphigus

Additional relevant MeSH terms:

Anti-Infective Agents
Antiprotozoal Agents
Autoimmune Diseases
Molecular Mechanisms of Pharmacological Action
Skin Diseases, Vesiculobullous
Skin Diseases
Immune System Diseases
Enzyme Inhibitors
Folic Acid Antagonists

Pharmacologic Actions
Pemphigus
Anti-Bacterial Agents
Antimalarials
Antiparasitic Agents
Therapeutic Uses
Dapsone
Leprostatic Agents

ClinicalTrials.gov processed this record on May 07, 2009