| CTRI Number |
CTRI/2018/12/016531 [Registered on: 05/12/2018] Trial Registered Prospectively |
| Last Modified On: |
28/11/2019 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Biological |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
To assess by a randomised,pilot study which of the two treatment regimens i.e. Rituximab infusion or Dexamethasone pulse therapy is more efficacious in the treatment of pemphigus vulgaris and relationship of various immunological parameters in skin and blood |
|
Scientific Title of Study
|
A randomized controlled pilot trial to compare the efficacy of Rituximab infusion versus intravenous Dexamethasone Pulse therapy in Pemphigus vulgaris and its correlation with phenotypic and functional determinants of B and T cells |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr SUJAY KHANDPUR |
| Designation |
PROFESSOR |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
4071, TEACHING BLOCK, DEPARTMENT OF DERMATOLOGY AND VENEREOLOGY, AIIMS, NEW DELHI
New Delhi
DELHI
110029
India |
| Phone |
01126594442 |
| Fax |
|
| Email |
sujay_khandpur@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
PREETI SHARMA |
| Designation |
PhD SCHOLAR |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
4071, TEACHING BLOCK, DEPARTMENT OF DERMATOLOGY AND VENEREOLOGY, AIIMS, NEW DELHI
New Delhi
DELHI
110029
India |
| Phone |
8467997961 |
| Fax |
|
| Email |
preeti.s1008@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr SUJAY KHANDPUR |
| Designation |
PROFESSOR |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
4071, TEACHING BLOCK, DEPARTMENT OF DERMATOLOGY AND VENEREOLOGY, AIIMS, NEW DELHI
New Delhi
DELHI
110029
India |
| Phone |
01126594442 |
| Fax |
|
| Email |
sujay_khandpur@yahoo.com |
|
|
Source of Monetary or Material Support
|
| ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI |
|
|
Primary Sponsor
|
| Name |
DR SUJAY KHANDPUR |
| Address |
4071, TEACHING BLOCK, DEPARTMENT OF DERMATOLOGY AND VENEREOLOGY, AIIMS, NEW DELHI |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| PREETI SHARMA |
4071, TEACHING BLOCK, DEPARTMENT OF DERMATOLOGY AND VENEREOLOGY, AIIMS, NEW DELHI |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DR SUJAY KHANDPUR |
DEPARTMENT OF DERMATOLOGY AND VENEREOLOGY |
AIIMS, NEW DELHI
New Delhi
DELHI |
01126594442
sujay_khandpur@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| AIIMS NEW DELHI |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: L100||Pemphigus vulgaris, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
DEXAMETHASONE |
Each pulse will consist of 3 days cycle of intravenous dexamethasone 100mg given in 500ml of 5% dextrose. This cycle will be repeated every 28 days.
Dexamethasone pulse therapy will be administered in two phases:
a) Phase I – DP administered for 3 days every month until patient attains disease control
b) Phase II – After disease control (completion of phase I), 6 cycles of DP will be administered
|
| Intervention |
RITUXIMAB |
INTRAVENOUS INFUSION OF 2 DOSES, 1 g EACH AT DAY 1 AND 15. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
Subject with active PV fulfilling any of the two criteria mentioned below:
-Clinical signs typical of pemphigus vulgaris and
-Histological features of suprabasal acantholysis on hematoxylin and eosin staining
-Positive ELISA test for anti dsg1 and dsg3 antibodies
2. Patients giving consent for obtaining blood and skin biopsy samples for various investigations
3. Patients who can obtain i.v. Rituximab (1g 2 doses)
|
|
| ExclusionCriteria |
| Details |
1.Pure mucosal pemphigus vulgaris
2.Age <18 or > 70 years
3.Has received prior biological therapy in past 2 months
4.Pregnant or lactating women.
5.Patients with severe renal or hepatic disease
6.Evidence of paraneoplastic pemphigus
7.Autoimmune blistering disease other than PV
8.Active, unhealed peptic ulcer within 3 months prior to randomization
9.Inherited or acquired immune deficiency
10.Malignancy, lymphoproliferative diseases or previous total lymphoid irradiation
11.Chronic or frequent drug resistant, bacterial infections or presence of severe active infection
12.Bone marrow insufficiency
13.Frequent and / or serious viral infections.
14.Systemic or invasive fungal disease within 2 years prior to randomization
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
An Open list of random numbers |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Median time to achieve complete disease remission in Rituximab infusion versus intravenous Dexamethasone pulse therapy group |
24months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Median time to achieve disease control in the 2 groups
|
24months |
| Number of patients in complete remission at 6 months and one year |
24months |
Percentage change in PDAI score and functional disability score
|
24months |
Number of patients with relapse in both groups
|
32months |
Cumulative dose of prednisolone in both groups
|
32months |
Cost effectiveness analysis between the two groups
|
32months |
Clinical adverse events in both groups assessed in terms of causality, severity and seriousness
|
32months |
| Median time to develop relapse in both groups |
32months |
Comparison of levels of circulating and lesional T-regulatory and B-regulatory cells between the 2 groups
|
32months |
Determination of biomarkers that would predict disease relapse in two groups:
a) levels of BAFF and APRIL ligands and BAFF R, TACI and BCMA receptors to predict relapse of disease
b) levels of CD4 T cells, CD19 B cell and anti desmoglein1 and desmoglein3 auto-antibodies in circulation
|
32months |
|
|
Target Sample Size
|
Total Sample Size="50"
Sample Size from India="50"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
15/12/2018 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NOT APPLICABLE |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Pemphigus vulgaris is a chronic autoimmune muco-cutaneous blistering disease which presents as a dermatological emergency as it predisposes to widespread secondary infection and sepsis, thermal dysregulation, electrolyte imbalance and even death. Treatment of pemphigus vulgaris remains a challenge because of the chronic, persistent nature and high rate of disease recurrence. Dexamethasone pulse therapy has been the mainstay of treatment for PV in India with long term remissions, cost-effective and a good safety profile. However, certain limitations such as long duration of supervised treatment (1-2 years) left scope for an alternative treatment with better efficacy in shorter time with fewer side effects. Rituximab is anti CD 20 monoclonal antibody and has been successfully used as intravenous infusion to treat recalcitrant pemphigus vulgaris, with good safety profile and clinical remission rates approaching 75%. We propose to compare clinical efficacy of the standard pulse therapy with rituximab treatment, safety profile of the two regimens and cost-effectiveness between the two regimens in a randomized trial. In addition, we also propose to compare changes in various biochemical and immunological parameters both in skin and blood during different periods of disease activity to assess efficacy of the two regimens and predict disease relapse. These biomarkers will help us in identification of patients at risk of relapse to avoid unnecessary infusions and significant cost savings. |