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

Primary Purpose

Bullous Pemphigoid

Status
Recruiting
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Prednisolone
Dapsone
Methotrexate
Sponsored by
All India Institute of Medical Sciences, Bhubaneswar
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bullous Pemphigoid focused on measuring Bullous pemphigoid, Methotrexate, Dapsone, BP180, Blister, Erosions

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • AIIMS BhubaneswarRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Prednisolone and Methotrexate (Control Arm)

Prednisolone and Dapsone (Test Arm)

Arm Description

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

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

Outcomes

Primary Outcome Measures

change in BPDAI (Bullous Pemphigoid Disease Area Index) score
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
change in serum BP180 after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
the remission rate
remission is defined as complete subsidence of all lesions without prednisolone or minimal prednisolone dose of 10 mg or less
the cumulative prednisolone dose
cumulative prednisolone dose after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
time to the initial flare
time to the initial flare after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
number of flares in study groups
number of flares in study groups after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
change in the Dermatological life quality index (DLQI)
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
treatment-emergent adverse events in both the groups

Full Information

First Posted
July 24, 2023
Last Updated
October 4, 2023
Sponsor
All India Institute of Medical Sciences, Bhubaneswar
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1. Study Identification

Unique Protocol Identification Number
NCT05984381
Brief Title
Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid
Official Title
Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
All India Institute of Medical Sciences, Bhubaneswar

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bullous Pemphigoid
Keywords
Bullous pemphigoid, Methotrexate, Dapsone, BP180, Blister, Erosions

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
randomized, add-on, active-controlled, open-label, parallel-design clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Prednisolone and Methotrexate (Control Arm)
Arm Type
Active Comparator
Arm Description
prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Methotrexate 15 mg weekly for 16 weeks.
Arm Title
Prednisolone and Dapsone (Test Arm)
Arm Type
Experimental
Arm Description
prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) and Dapsone 100 mg/day for 16 weeks
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
prednisolone 0.75mg/kg/day (a maximum dose of 40mg at baseline) orally
Intervention Type
Drug
Intervention Name(s)
Dapsone
Intervention Description
Dapsone 100 mg/day
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Methotrexate 15 mg weekly
Primary Outcome Measure Information:
Title
change in BPDAI (Bullous Pemphigoid Disease Area Index) score
Description
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
Time Frame
8 weeks and 16 weeks
Secondary Outcome Measure Information:
Title
change in serum BP180
Description
change in serum BP180 after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
Time Frame
16 weeks
Title
the remission rate
Description
remission is defined as complete subsidence of all lesions without prednisolone or minimal prednisolone dose of 10 mg or less
Time Frame
8 weeks and 16 weeks
Title
the cumulative prednisolone dose
Description
cumulative prednisolone dose after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
Time Frame
16 weeks
Title
time to the initial flare
Description
time to the initial flare after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
Time Frame
16 weeks
Title
number of flares in study groups
Description
number of flares in study groups after treatment with prednisolone and methotraxate Vs Prednisolone and dapsone
Time Frame
16 weeks
Title
change in the Dermatological life quality index (DLQI)
Description
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.
Time Frame
8 weeks and 16 weeks
Title
treatment-emergent adverse events
Description
treatment-emergent adverse events in both the groups
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Monalisa Jena, MD
Phone
9438884193
Email
pharm_monalisa@aiimsbhubaneswar.edu.in
First Name & Middle Initial & Last Name or Official Title & Degree
Biswanath Behera, MD
Phone
7978351200
Email
Dermat_biswanath@aiimsbhubaneswar.edu.in
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rituparna Maiti, MD
Organizational Affiliation
Professor
Official's Role
Study Director
Facility Information:
Facility Name
AIIMS Bhubaneswar
City
Bhubaneswar
State/Province
Odisha
ZIP/Postal Code
751019
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monalisa Jena, MD
Phone
9438884193
Email
pharm_monalisa@aiimsbhubaneswar.edu.in
First Name & Middle Initial & Last Name & Degree
Biswanath Behera
First Name & Middle Initial & Last Name & Degree
Madhusmita Sethy
First Name & Middle Initial & Last Name & Degree
Richardson M

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35080093
Citation
Lu L, Chen L, Xu Y, Liu A. Global incidence and prevalence of bullous pemphigoid: A systematic review and meta-analysis. J Cosmet Dermatol. 2022 Oct;21(10):4818-4835. doi: 10.1111/jocd.14797. Epub 2022 Feb 1.
Results Reference
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PubMed Identifier
35427358
Citation
Chen X, Zhang Y, Luo Z, Wu Y, Niu T, Zheng J, Xie Y. Prognostic factors for mortality in bullous pemphigoid: A systematic review and meta-analysis. PLoS One. 2022 Apr 15;17(4):e0264705. doi: 10.1371/journal.pone.0264705. eCollection 2022.
Results Reference
background
PubMed Identifier
31312206
Citation
Genovese G, Di Zenzo G, Cozzani E, Berti E, Cugno M, Marzano AV. New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update. Front Immunol. 2019 Jul 2;10:1506. doi: 10.3389/fimmu.2019.01506. eCollection 2019.
Results Reference
background
PubMed Identifier
18665656
Citation
Patton T, Korman N. Role of methotrexate in the treatment of bullous pemphigoid in the elderly. Drugs Aging. 2008;25(8):623-9. doi: 10.2165/00002512-200825080-00001.
Results Reference
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PubMed Identifier
21497011
Citation
Tirado-Sanchez A, Diaz-Molina V, Ponce-Olivera RM. Efficacy and safety of azathioprine and dapsone as an adjuvant in the treatment of bullous pemphigoid. Allergol Immunopathol (Madr). 2012 May-Jun;40(3):152-5. doi: 10.1016/j.aller.2010.12.009. Epub 2011 Apr 14.
Results Reference
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PubMed Identifier
28494097
Citation
Sticherling M, Franke A, Aberer E, Glaser R, Hertl M, Pfeiffer C, Rzany B, Schneider S, Shimanovich I, Werfel T, Wilczek A, Zillikens D, Schmidt E. An open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone. Br J Dermatol. 2017 Nov;177(5):1299-1305. doi: 10.1111/bjd.15649. Epub 2017 Oct 29.
Results Reference
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PubMed Identifier
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Citation
Rashid H, Lamberts A, Diercks GFH, Pas HH, Meijer JM, Bolling MC, Horvath B. Oral Lesions in Autoimmune Bullous Diseases: An Overview of Clinical Characteristics and Diagnostic Algorithm. Am J Clin Dermatol. 2019 Dec;20(6):847-861. doi: 10.1007/s40257-019-00461-7.
Results Reference
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Citation
Reunala T, Salmi TT, Hervonen K. Dermatitis herpetiformis: pathognomonic transglutaminase IgA deposits in the skin and excellent prognosis on a gluten-free diet. Acta Derm Venereol. 2015 Nov;95(8):917-22. doi: 10.2340/00015555-2162.
Results Reference
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Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid

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