Clinical trial NCT03775460: Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum
Official title: Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum (MaPS in ENL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Erythema Nodosum Leprosum
Keywords: Erythema Nodosum Leprosum
ENL
corticosteroids
Methotrexate
ENL severity scale
quality of life
Leprosy
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Dr. Soetomo General Hospital
name: The Leprosy Mission Trust, India
name: Alert Hospital, Ethiopia
name: The Leprosy Mission Bangladesh
name: Bombay Leprosy Project, India
name: Oswaldo Cruz Foundation
name: Leprosy Research Initiative
name: The Leprosy Mission Nepal
First posted: 2018-12-14
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Erythema Nodosum Leprosum (ENL) is a painful, debilitating complication of leprosy. Patients often require high doses of corticosteroids for prolonged periods. Thalidomide is expensive and not available in most countries. The use of corticosteroids for long periods is associated with adverse effects and mortality. It is a priority to identify alternative agents to treat ENL. Methotrexate (MTX) is a cheap, widely used medication which has been reported to be effective in ENL resistant to steroids and thalidomide.

Detailed description: This is a double blind randomized controlled trial (RCT) to test the efficacy of MTX for managing ENL. Patients diagnosed with moderate or severe ENL at ENLIST Group centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal will be randomly allocated to receive a 15 or 20 mg of oral MTX each week for 48 weeks and prednisolone 40 mg per day reducing to zero over 20 weeks. The control group will receive an identical prednisolone scheme. The participants will be stratified into two groups, those with acute ENL, those with chronic/recurrent ENL. The interventions for both populations are the same, although analysed separately. Adverse effects (AE) will be closely monitored clinically and using laboratory tests. Participants will receive folic acid, 5mg daily for 52 weeks except on the day of MTX to prevent AEs, and nausea will be managed with ondansetron.

Eligibility criteria: Inclusion Criteria:: ALL OF THE FOLLOWING SIX CRITERIA MUST BE MET IN ORDER FOR AN INDIVIDUAL TO BE ELIGIBLE (ONLY ONE OF 6A TO 6D NEED BE MET):

1. Individuals who diagnosed with leprosy complicated by ENL
2. Individuals with ENL aged 18-60 years old
3. Individuals with ENL deteriorating symptoms
4. Individuals with 10 or more tender, papular or nodular ENL skin lesions
5. Individuals with an EESS score of at least 9
6. Individuals with ENL on:

   1. No current anti- ENL treatment
   2. Prednisolone up to 30mg per day (if ACUTE) or Prednisolone 10-30mg (inclusive) per day (if RECURRENT/ CHRONIC) or equivalent alternative corticosteroid dose OR
   3. Thalidomide or other non-steroidal anti-ENL medication OR
   4. A combination of prednisolone (up to 30mg) and another non-steroidal anti-ENL medication (thalidomide, clofazimine, azathioprine, pentoxifylline, ciclosporin, minocycline)

Exclusion criteria:

1. Individuals who were first diagnosed with ENL more than 4 years prior to enrolment
2. Individuals less than 18 years old or older than 60 years
3. Individuals weighing less than 35kg
4. Individuals with 9 or fewer tender, popular or nodular ENL skin lesions
5. Individuals with an EESS score of 8 or less
6. Women of child bearing capacity who decline to use two forms of adequate contraception and men who decline to use two forms of adequate contraception
7. Pregnant or breastfeeding women
8. Individuals with recurrent or chronic ENL who deteriorate on a dose of prednisolone less than 10 mg or more than 30 mg
9. Individuals who have taken methotrexate by any route for the last 12 weeks
10. Individuals with a hypersensitivity to methotrexate or a recognised contraindication ( please see Methotrexate information sheet)
11. Individuals currently diagnosed with Type 1 reaction or Lucio's phenomenon
12. Individuals with the severe abnormalities in screening investigations
13. Positive serology for HIV, Hepatitis B or C
14. Evidence of tuberculosis or pulmonary fibrosis
15. A history of chronic liver disease or excessive alcohol or illicit substance consumption
16. Individuals with severe inter-current infections, uncontrolled diabetes, active peptic ulcer disease, untreated malignancy
17. Individuals unable to attend regularly for assessment or monitoring

Primary outcomes:
measure: Proportion of individuals free from Erythema Nodosum Leprosum (ENL) flares in 24 weeks
timeFrame: During the first 24 weeks
measure: Proportion of individuals free from ENL flares in 48 weeks
timeFrame: During first 48 weeks
Secondary outcomes:
measure: Change in ENLIST ENL severity scale score (EESS)
timeFrame: 60 weeks
measure: Quality of life changes: 36- Item Short Form (SF-36) questionnaire
timeFrame: at 24 and 48 weeks
measure: Quality of life changes regarding skin condition: Dermatology life quality Index (DLQI)
timeFrame: at 24 and 48 weeks
measure: Proportion of individuals free from ENL flares at 60 weeks
timeFrame: 60 weeks
measure: ENL flares per individual up to 60 weeks
timeFrame: 60 weeks
measure: Severity of ENL flares
timeFrame: 60 weeks
measure: Time to the first flare of ENL
timeFrame: 60 weeks
measure: Adverse effects
timeFrame: 60 weeks
measure: Quality of life at 60 weeks: SF-36 questionnaire
timeFrame: 60 weeks
measure: Quality of life at 60 weeks regarding skin condition: Dermatology Life Quality Index (DLQI) questionnaires
timeFrame: 60 weeks
measure: Individuals free from ENL flares in 60 weeks
timeFrame: 60 weeks
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: TMLI Bangladesh/ DBLM hospital
city: Rio De Janeiro
country: Brazil
facility: FIOCRUZ
city: Addis Ababa
country: Ethiopia
facility: ALERT
city: Delhi
country: India
facility: The Leprosy Mission Trust
city: Mumbai
country: India
facility: Bombay Leprosy Project
city: Surabaya
country: Indonesia
facility: Soetomo Hospital
city: Kathmandu
country: Nepal
facility: Anandaban Hospital
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Stephen Walker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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