| CTRI Number |
CTRI/2024/07/070083 [Registered on: 05/07/2024] Trial Registered Prospectively |
| Last Modified On: |
28/06/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A study to compare the safety and side effect profile of Thalidomide versus Methotrexate in patients of type 2 Lepra Reaction |
|
Scientific Title of Study
|
The Efficacy and Safety of Thalidomide versus Methotrexate in Erythema Nodosum Leprosum (ENL): A Randomized Controlled Trial |
| Trial Acronym |
nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Bhini Ameta |
| Designation |
Junior Resident |
| Affiliation |
All India Institute of Medical Sciences, Bhubaneswar |
| Address |
Room 139, Department of Dermatology, Venereology and Leprosy
All India Institute of Medical Sciences,Bhubaneswar, Patrapada, Sijua, Bhubaneswar, Odisha 751019
Khordha
ORISSA
751019
India |
| Phone |
90799239817 |
| Fax |
|
| Email |
ametabhini@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Biswanath Behera |
| Designation |
Associate Professor |
| Affiliation |
All India Institute of Medical Sciences, Bhubaneswar |
| Address |
Room 139, Department of Dermatology, Venereology and Leprosy ,
All India Institute of Medical Sciences, Bhubaneswar, Patrapada, Sijua
Khordha
ORISSA
751019
India |
| Phone |
7978351200 |
| Fax |
|
| Email |
biswanathbehera61@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Biswanath Behera |
| Designation |
Associate Professor |
| Affiliation |
All India Institute of Medical Sciences, Bhubaneswar |
| Address |
Room 139, Department of Dermatology, Venereology and Leprosy ,
All India Institute of Medical Sciences, Bhubaneswar, Patrapada, Sijua
Khordha
ORISSA
751019
India |
| Phone |
7978351200 |
| Fax |
|
| Email |
biswanathbehera61@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences, Bhubaneswar
Patrapada, Sijua, Bhubaneswar, Odisha, India 751019 |
|
|
Primary Sponsor
|
| Name |
Dr Bhini Ameta |
| Address |
Room 139, Department of Dermatology, Venereology and Leprosy, All India Institute of Medical Sciences, Bhubaneswar, Patrapada, Sijua, Odisha 751019 |
| Type of Sponsor |
Other [Self] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Bhini Ameta |
All India Institute of Medical Sciences, Bhubaneswar |
Department of Dermatology, Venereology and Leprosy
All India Institute of Medical Sciences, Bhubaneswar, Patrapada, Sijua, Odisha, 751019
Khordha
ORISSA |
9079923817
ametabhini@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee , All India Institute of Medical Sciences, Bhubaneswar |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: A305||Lepromatous leprosy, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Methotrexate |
The patients will receive prednisolone 1mg/kg/day or a maximum dose of 60mg at baseline along with methotrexate.
Methotrexate 15 mg once weekly will be continued till the last follow-up of 6 months.
Patients will be advised contraception till three month after the stop of therapy.
Tapering schedule of prednisolone: Week 1-2 (60mg), Week 3-4 (50mg), Week 5-6 (40mg), Week 7-8 (30mg), Week 9-10 (20mg), Week 11-12 (15mg), Week 13-14 (10mg), Week 15-16 (5mg), stop
|
| Comparator Agent |
Thalidomide |
The patients will receive prednisolone 1mg/kg/day or a maximum dose of 60mg at baseline along with thalidomide 100mg four times daily for one week followed by 100mg three times daily till prednisolone is stopped. Following this thalidomide will be given by 100mg twice daily for two months and followed by 100mg once daily till the last follow up or 6 months whichever is later. Counselling of the patients taking thalidomide will be done by the following the system for thalidomide education and prescribing safety (STEPS) protocol. Women in the reproductive age group will be tested for pregnancy before the start of the drug and counselled to adopt dual contraceptive methods comprising of a highly effective method along with a barrier method 4 weeks before, throughout and for 4 weeks after the end of therapy. Male patients will also be advised to use a barrier contraceptive method at the initiation of treatment and up to 1 month after the completion of treatment.
Tapering schedule of prednisolone: Week 1-2 (60mg), Week 3-4 (50mg), Week 5-6 (40mg), Week 7-8 (30mg), Week 9-10 (20mg), Week 11-12 (15mg), Week 13-14 (10mg), Week 15-16 (5mg), stop |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
1.Patients with severe ENL of any gender and age more than 18 years
2.Patients willing to participate and willing to follow up for six months
Definitions:
Erythema nodosum leprosum (ENL): It is defined as the sudden appearance of transient painful erythematous cutaneous nodules mostly on the extensor aspects of legs and arms, face along with occasional involvement of the trunk.
New ENL: is defined as ENL occurring 1st time in a patient.
Nature of ENL classified as:
Acute ENL- one ENL episode lasting for less than 24 weeks while the patient is on corticosteroid treatment.
Recurrent ENL- if a patient develops ENL again after 28 days of stoppage of treatment.
Chronic ENL- ENL lesions persist for greater than or 24 weeks while the patient is on treatment continuously/having treatment free period for 27 days or less
Mild ENL: It affects only the skin along with low grade fever and ENLIST ENL severity score is less than or equal to 8.
Severe ENL: It is characterized by multiple cutaneous nodules which may ulcerate, along with the inflammation of other organs such as the nerves, eyes, joints, testes, and lymph nodes. The ENLIST ENL score more than 8.
|
|
| ExclusionCriteria |
| Details |
1.Patients with known immunosuppression or on immunosuppressive therapy
2.Patients with severe ENL on any steroid-sparing agents within the last one month
3.Pregnancy and lactation
4.Patients with a history of hypersensitivity to thalidomide or methotrexate.
5.Patients with haemoglobin less than 10 gm/dl, Leukopenia (total leukocyte count less than 4000/mm3), or thrombocytopenia (Platelets less than 1lakh/mm3), active liver disease (AST, ALT more han 35 IU/L), eGFR less than 30 ml/min/1.73 m2
6.Patients with HIV 1 and or 2, Hepatitis B and C infection.
7.Patients on therapy that interacts with interventional drugs
8.Patients with a self-declared history of alcohol consumption.
9.Patients who will deny giving consent to the study
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Case Record Numbers |
|
Blinding/Masking
|
Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To compare the proportion of patients achieving remission at three and six months (Remission is defined as subsidence of all features of ENL with ENL International Study Group Severity Scale score of zero when the patient is off prednisolone or minimal prednisolone dose of 10mg or less) between the Thalidomide group and Methotrexate group |
Baseline, 3 month, 6 month |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
i. The number of ENL flares
ii. The mean time for ENL flare
iii. Cumulative dose of steroids in both groups
iv. Percentage change in DLQI
v. The correlation between ENLIST ENL severity score and serum IL 6 levels
vi. The correlation between ENLIST ENL severity score and pretibial tenderness
vii. Histopathological-dermoscopic correlation of skin lesions
|
6 month |
|
|
Target Sample Size
|
Total Sample Size="46"
Sample Size from India="46"
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 4 |
|
Date of First Enrollment (India)
|
20/07/2024 |
| 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="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
- What data in particular will be shared?
Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
- What additional supporting information will be shared?
Response - Study Protocol
Response - Statistical Analysis Plan
Response - Informed Consent Form
Response - Clinical Study Report
- Who will be able to view these files?
Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
- For what types of analyses will this data be available?
Response - To achieve aims in the approved proposal.
- By what mechanism will data be made available?
Response - Proposals should be directed to [ametabhini@gmail.com].
- For how long will this data be available start date provided 20-09-2026 and end date provided 20-06-2031?
Response - Beginning 3 months and ending 5 years following article publication.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL
|
|
Brief Summary
|
This is a single-blinded, randomized, controlled, non-inferiority trial being conducted at a tertiary care institute in Eastern India. The primary objective of this trial is to assess the safety and efficacy of methotrexate in erythema nodosum leprosum and compare it with thalidomide. A total of 46 patients meeting the inclusion and exclusion criteria will be recruited and randomized into two groups (23 each) using computer-generated randomization sequences. One group will receive oral methotrexate with prednisolone, and another group will receive oral thalidomide with prednisolone. Both the groups will be followed up for a period of 6 months and will be assessed for response to treatment (using EESS score) and adverse effects of the drugs, if any. Routine lab monitoring will be done as per protocol. Data will be recorded in hard copy in the form of pre-designed proforma and soft copy in the form of an Excel sheet. Statistical analysis will be done using SPSS software version 27. Approval is taken from the Institute Ethics Committee, All India Institute of Medical Sciences, Bhubaneswar. Informed consent will be taken from all participants and the study will follow ICMR and GCP guidelines |