Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid

Sponsor

All India Institute of Medical Sciences, Bhubaneswar (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05984381

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder most commonly affecting the older population between 60-80 years old. The characteristic feature of BP is itchy patches associated with blisters and erosions. BP significantly affects the patient's quality of life as it causes physical discomfort with itchy patches, blisters, and erosions. Several pieces of evidence from previous studies showed that the production of autoantibodies against the hemidesmosomal anchoring proteins BP180 (Bullous Pemphigoid antigen (BPAG 2)) and BP230 (BPAG 1) is the most common cause for bullous pemphigoid.

Therapeutic latency, lack of efficacy in many patients, and adverse drug reactions are the primary concerns in the current bullous pemphigoid treatment paradigm, including high-dose steroid treatment. To overcome these treatment challenges, combination therapy with agents having a steroid-sparing effect like mycophenolate mofetil, cyclophosphamide, azathioprine, and Methotrexate are tested as an add-on to low-dose steroids. 8So other immunosuppressive agents with better safety profiles and more efficacy, like Dapsone and Methotrexate as an add-on to low-dose steroids, can be used.

Investigator's literature search found no randomized controlled trial with Dapsone versus Methotrexate as an add-on to first-line steroid has been conducted to compare the efficacy and safety in bullous pemphigoid patients. So, a randomized controlled trial has been planned to evaluate the safety and efficacy of add-on methotrexate versus Dapsone in bullous pemphigoid patients.

Condition or Disease	Intervention/Treatment	Phase
Bullous Pemphigoid	Drug: Prednisolone Drug: Dapsone Drug: Methotrexate	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized, add-on, active-controlled, open-label, parallel-design clinical trialrandomized, add-on, active-controlled, open-label, parallel-design clinical trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid: A Randomized Controlled Trial

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Aug 31, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Prednisolone and Methotrexate (Control Arm) prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Methotrexate 15 mg weekly for 16 weeks.	Drug: Prednisolone prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally Drug: Methotrexate Methotrexate 15 mg weekly
Experimental: Prednisolone and Dapsone (Test Arm) prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Dapsone 100 mg/day for 16 weeks	Drug: Prednisolone prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally Drug: Dapsone Dapsone 100 mg/day

Arm

Intervention/Treatment

Active Comparator: Prednisolone and Methotrexate (Control Arm)

prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Methotrexate 15 mg weekly for 16 weeks.

Drug: Prednisolone

prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally

Drug: Methotrexate

Methotrexate 15 mg weekly

Experimental: Prednisolone and Dapsone (Test Arm)

prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Dapsone 100 mg/day for 16 weeks

Drug: Prednisolone

prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally

Drug: Dapsone

Dapsone 100 mg/day

Outcome Measures

Primary Outcome Measures

change in BPDAI (Bullous Pemphigoid Disease Area Index) score [8 weeks and 16 weeks]
change in BPDAI (Bullous Pemphigoid Disease Area Index) score after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone Score range from 0-360 (Minimum 0 and maximum 360) higher scores indicating greater disease activity

Secondary Outcome Measures

change in serum BP180 [16 weeks]
change in serum BP180 after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
the remission rate [8 weeks and 16 weeks]
remission is defined as complete subsidence of all lesions without prednisolone or minimal prednisolone dose of 10 mg or less
the cumulative prednisolone dose [16 weeks]
cumulative prednisolone dose after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
time to the initial flare [16 weeks]
time to the initial flare after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
number of flares in study groups [16 weeks]
number of flares in study groups after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
change in the Dermatological life quality index (DLQI) [8 weeks and 16 weeks]
change in the Dermatological life quality index (DLQI) after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone maximum of 30 and a minimum of 0 The higher the score, the more quality of life is impaired.
treatment-emergent adverse events [16 weeks]
treatment-emergent adverse events in both the groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged ≥18 of either sex with the clinical diagnosis of Bullous pemphigoid.
Patients with BPDAI score ≥ 20 (moderate and severe BP).
Patients must have characteristic clinical features of bullous pemphigoid at the screening and baseline visits. (Urticaria, bullae, pruritis).
Patients who are willing to give informed written consent.

Exclusion Criteria:

Patients on any steroid-sparing agents within one month of recruitment.
Treatment with a systemic corticosteroid, sulfones, within the last week.
Patients with Glucose 6 phosphate dehydrogenase deficiency.
Decreased liver or renal function (creatinine > 2.0mg/dl, total bilirubin > 2.5 mg/dl).
Severe acute infection, severe diabetes mellitus, untreated glaucoma, congenital or acquired immunodeficiency, active gastroduodenal ulcer, severe osteoporosis, severe cardiac disease (NYHA grade IV), MI in the last four weeks, severe schizophrenia or depression.
Malignancies treated by cytotoxic or immunosuppressive medications.
Anaemia (Hb <9 gm/dl), leucopenia (< 3 ×10 9 cells /L) or thrombocytopenia (< 100 × 10 9 cells/ L), and H/O porphyria.
Patient with a history of hypersensitivity to Methotrexate or Dapsone.
Vaccination in the last two weeks.
Patients with HIV, Hepatitis B, and C infection.
Pregnancy and lactation, women of childbearing age without effective contraception.