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Trial record 5 of 5 for:    "Hansen's Disease" | "Prednisolone"

Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum (MaPs)

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ClinicalTrials.gov Identifier: NCT03775460
Recruitment Status : Not yet recruiting
First Posted : December 14, 2018
Last Update Posted : August 13, 2019
Sponsor:
Collaborators:
Dr. Soetomo General Hospital
The Leprosy Mission Trust, India
Alert Hospital, Ethiopia
The Leprosy Mission Bangladesh
Bombay Leprosy Project, India
Oswaldo Cruz Foundation
Leprosy Research Initiative
The Leprosy Mission Nepal
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Tracking Information
First Submitted Date  ICMJE November 29, 2018
First Posted Date  ICMJE December 14, 2018
Last Update Posted Date August 13, 2019
Estimated Study Start Date  ICMJE January 1, 2020
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2019)
  • Proportion of individuals free from Erythema Nodosum Leprosum (ENL) flares in 24 weeks [ Time Frame: During the first 24 weeks ]
    Proportion of individuals who have not required additional prednisolone during the first 24 weeks. The aim is to evaluate if individuals in the methotrexate regimen will need less prednisolone than the control arm.
  • Proportion of individuals free from ENL flares in 48 weeks [ Time Frame: During first 48 weeks ]
    Proportion of individuals who have not required additional prednisolone during the first 48 weeks. To evaluate if methotrexate will be more efficient to control ENL than only prednisolone
Original Primary Outcome Measures  ICMJE
 (submitted: December 13, 2018)
  • Proportion of individuals free from ENL flares in 24 weeks [ Time Frame: During the first 24 weeks ]
    Proportion of individuals who have not required additional prednisolone during the first 24 weeks. The aim is to evaluate if individuals in the methotrexate regimen will need less prednisolone than the control arm.
  • Proportion of individuals free from ENL flares in 48 weeks [ Time Frame: During first 48 weeks ]
    Proportion of individuals who have not required additional prednisolone during the first 48 weeks. To evaluate if methotrexate will be more efficient to control ENL than only prednisolone
Change History Complete list of historical versions of study NCT03775460 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2019)
  • Change in ENLIST ENL severity scale score (EESS) [ Time Frame: 60 weeks ]
    ENLIST group (Erythema Nodosum Leprosum International STudy) developed and validated a severity scale for ENL, which consist 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the change in ENLIST ENL Severity Scale score from baseline to the first flare of ENL requiring additional prednisolone
  • Quality of life changes: 36- Item Short Form (SF-36) questionnaire [ Time Frame: at 24 and 48 weeks ]
    Change in patient reported health-related quality of life at 24 and 48 weeks from baseline. This will be measured by 36- Item Short Form (SF-36) questionnaire developed by RAND, validated worldwide. The SF-36 consists of 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. If the score is 0 is equivalent to maximum disability. The 8 sections are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, emotional role functioning, social role functioning and mental health.
  • Quality of life changes regarding skin condition: Dermatology life quality Index (DLQI) [ Time Frame: at 24 and 48 weeks ]
    Change in patient reported health-related quality of life at 24 and 48 weeks, specific to skin condition, such as ENL. It will be used the Dermatology life quality Index (DLQI),which is a questionnaire of 10 questions to specific evaluate quality of life in dermatologic conditions.The score can range from 0 to 30, meaning 0 no effect at all on patient's life to 30 extremely large effect on patient's life.
  • Proportion of individuals free from ENL flares at 60 weeks [ Time Frame: 60 weeks ]
    Proportion of individuals who do not require prednisolone at 60 weeks
  • ENL flares per individual up to 60 weeks [ Time Frame: 60 weeks ]
    Number of flares of ENL per individual requiring additional prednisolone up to 60 weeks
  • Severity of ENL flares [ Time Frame: 60 weeks ]
    As stated on outcome 3, the severity of ENL will be measured by ENLIST ENL severity scale. The scale is composed by 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the maximum severity of flares of ENL requiring additional prednisolone up to 60 weeks
  • Time to the first flare of ENL [ Time Frame: 60 weeks ]
    How long it takes to a participant who has an ENL flare to present with first episode of flare after enrolment
  • Adverse effects [ Time Frame: 60 weeks ]
    Proportion of individuals with treatment related adverse effects
  • Quality of life at 60 weeks: SF-36 questionnaire [ Time Frame: 60 weeks ]
    As described on outcome 4. We will use SF-36 questionnaire to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline
  • Quality of life at 60 weeks regarding skin condition: Dermatology Life Quality Index (DLQI) questionnaires [ Time Frame: 60 weeks ]
    As described on outcome 5. We will use DLQI questionnaires to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline, specific to skin conditions such as ENL.
  • Individuals free from ENL flares in 60 weeks [ Time Frame: 60 weeks ]
    Proportion of individuals who have not required additional prednisolone in the 60 weeks of the trial
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2018)
  • Change in severity scale score [ Time Frame: 60 weeks ]
    ENLIST group (Erythema Nodosum Leprosum International STudy) developed and validated a severity scale for ENL, which consist 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the change in ENLIST ENL Severity Scale score from baseline to the first flare of ENL requiring additional prednisolone
  • Quality of life changes: 36- Item Short Form (SF-36) questionnaire [ Time Frame: at 24 and 48 weeks ]
    Change in patient reported health-related quality of life at 24 and 48 weeks from baseline. This will be measured by 36- Item Short Form (SF-36) questionnaire developed by RAND, validated worldwide. The SF-36 consists of 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. If the score is 0 is equivalent to maximum disability. The 8 sections are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, emotional role functioning, social role functioning and mental health.
  • Quality of life changes regarding skin condition: Dermatology life quality Index (DLQI) [ Time Frame: at 24 and 48 weeks ]
    Change in patient reported health-related quality of life at 24 and 48 weeks, specific to skin condition, such as ENL. It will be used the Dermatology life quality Index (DLQI),which is a questionnaire of 10 questions to specific evaluate quality of life in dermatologic conditions.The score can range from 0 to 30, meaning 0 no effect at all on patient's life to 30 extremely large effect on patient's life.
  • Proportion of individuals free from ENL flares at 60 weeks [ Time Frame: 60 weeks ]
    Proportion of individuals who do not require prednisolone at 60 weeks
  • ENL flares per individual up to 60 weeks [ Time Frame: 60 weeks ]
    Number of flares of ENL per individual requiring additional prednisolone up to 60 weeks
  • Severity of ENL flares [ Time Frame: 60 weeks ]
    As stated on outcome 3, the severity of ENL will be measured by ENLIST ENL severity scale. The scale is composed by 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the maximum severity of flares of ENL requiring additional prednisolone up to 60 weeks
  • Time to the first flare of ENL [ Time Frame: 60 weeks ]
    How long it takes to a participant who has an ENL flare to present with first episode of flare after enrolment
  • Adverse effects [ Time Frame: 60 weeks ]
    Proportion of individuals with treatment related adverse effects
  • Quality of life at 60 weeks: SF-36 questionnaire [ Time Frame: 60 weeks ]
    As described on outcome 4. We will use SF-36 questionnaire to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline
  • Quality of life at 60 weeks regarding skin condition: DLQI questionnaires [ Time Frame: 60 weeks ]
    As described on outcome 5. We will use DLQI questionnaires to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline, specific to skin conditions such as ENL.
  • Individuals free from ENL flares in 60 weeks [ Time Frame: 60 weeks ]
    Proportion of individuals who have not required additional prednisolone in the 60 weeks of the trial
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum
Official Title  ICMJE Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum (MaPS in ENL
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Erythema Nodosum Leprosum
Intervention  ICMJE
  • Drug: Methotrexate
    Participants in the intervention group will receive methotrexate along side prednisolone
  • Drug: Placebo
    Participants in the control arm will receive placebo along side prednisolone
  • Drug: Prednisolone
    Participants in both arm will receive prednisolone, which will be the same dosage: 40 mg (initial dose) decreasing dosage for 20 weeks
Study Arms  ICMJE
  • Placebo Comparator: control
    Participants will receive placebo+ prednisolone. Participants will start receiving 4 dummy tablets per week, than participants weighing less than 60 kg will receive 6 dummy tablets from week 8. The placebo will be prescribe weekly. Participants weighing 60 kg or more will receive 8 dummy tablets from week 8. Participants will receive dummy tablets for 52 weeks. Along with prednisolone. The start dose of prednisolone will be 40 mg per day decreasing dosage for 20 weeks.
    Interventions:
    • Drug: Placebo
    • Drug: Prednisolone
  • Experimental: intervention
    Participants will receive Methotrexate(MTX)+prednisolone. All participants in intervention arm will receive an initial dose of MTX 10 mg. The MTX will be increased to 15 mg the following week. Participants weighing less than 60 kg will continue to receive 15 mg of MTX weekly thereafter. Individuals weighing 60 kg or more will receive MTX 20 mg from week 8. At week 48 the MTX will be reduced to 10 mg for two weeks followed by 5 mg for two weeks and then stopped. In total participants will receive 52 weeks of MTX along side prednisolone, which will be the same as the control arm.
    Interventions:
    • Drug: Methotrexate
    • Drug: Prednisolone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 13, 2018)
550
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 1, 2022
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Barbara de Barros, M.D +44(0)2079272316 barbara.de-barros@lshtm.ac.uk
Listed Location Countries  ICMJE Bangladesh,   Brazil,   Ethiopia,   India,   Indonesia,   Nepal
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03775460
Other Study ID Numbers  ICMJE 15762
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party London School of Hygiene and Tropical Medicine
Study Sponsor  ICMJE London School of Hygiene and Tropical Medicine
Collaborators  ICMJE
  • Dr. Soetomo General Hospital
  • The Leprosy Mission Trust, India
  • Alert Hospital, Ethiopia
  • The Leprosy Mission Bangladesh
  • Bombay Leprosy Project, India
  • Oswaldo Cruz Foundation
  • Leprosy Research Initiative
  • The Leprosy Mission Nepal
Investigators  ICMJE
Principal Investigator: Stephen Walker, MD, PhD London School of Hygiene and Tropical Medicine
PRS Account London School of Hygiene and Tropical Medicine
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP