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Uniform Multidrug Therapy Regimen for Leprosy Patients (U-MDT)

Primary Purpose

Leprosy

Status
Completed
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
PB 6 doses - Rifampicin and Dapsone
PB 6 doses - Rifampicin, Clofazimine and Dapsone
MB 12 doses - Rifampicin, Clofazimine and Dapsone
MB 6 doses - Rifampicin, Clofazimine and Dapsone
Sponsored by
University of Brasilia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leprosy focused on measuring Leprosy, Communicable Diseases, Skin Diseases, Multidrug Therapy, MDT, Uniform Multidrug Therapy, U-MDT

Eligibility Criteria

6 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • All newly diagnosed leprosy cases with characteristic skin lesions, with or without systemic symptoms or confirmed by histopathological study previously untreated PB and MB leprosy patients.
  • Never treated or patient treated more than five years ago

Exclusion Criteria:

Safety concerns:

  • History of intolerance to one of the medications

Lack of suitability for the trial:

  • Absence of leprosy skin lesions
  • Pure neural leprosy (PNL)
  • Patient previously (defaulters and relapse) treated for leprosy less than 5 years ago
  • Association with other serious diseases such as HIV/AIDS, Tuberculosis, Malaria, American Cutaneous leishmaniasis, Visceral Leishmaniasis, Lymphoma, Leukaemia, Immunosuppression, etc.

Administrative reasons

  • Patients who are not permanent residents of the area or who are unable to come to the clinic every month during their treatment and in the first half year (the intensive follow-up period) after their treatment.
  • Patients who do not give informed consent or are not capable to give informed consent due to mental impairment.
  • Patients with overt signs of AIDS because it is unlikely that we can follow them up for the whole study period. As we will not be testing patients for HIV positivity, HIV-infected leprosy patients can be included in the study.

Sites / Locations

  • Centro de Referência Nacional Alfredo da Matta - FUAM
  • Centro de Referência Nacional Dona Libânia - CDERM

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Arm Label

R-MDT PB

U-MDT PB

R-MDT MB

U-MDT MB

Arm Description

R-MDT PB group: standard/regular treatment recommended by WHO - All patients presenting fewer than 6 skin lesions will receive the standard treatment regimen for paucibacillary patients as the intervention; Intervention - PB 6 doses of rifampicin and dapsone

U-MDT PB group: a unified treatment for all patients - All patients presenting fewer than 6 lesions (WHO PB) will receive 6 doses of rifampicin, clofazimine and dapsone as the intervention; Intervention - PB 6 doses of rifampicin, clofazimine and dapsone

R-MDT MB group: standard/regular treatment recommended by WHO - All patients presenting 6 skin or more lesions will receive the standard treatment regimen for multibacillary patients as the intervention; Intervention - MB 12 doses of rifampicin, clofazimine and dapsone

U-MDT MB group: a unified treatment for all patients - All patients presenting 6 lesions or more (WHO MB) will receive 6 doses of rifampicin, clofazimine and dapsone as the intervention; Intervention - MB 6 doses of rifampicin, clofazimine and dapsone

Outcomes

Primary Outcome Measures

Relapse

Secondary Outcome Measures

Type I Reaction - Reversal Reactions
Type II Reaction - Erythema nodosum leprosum
Neurological damage
Neuritis

Full Information

First Posted
April 24, 2008
Last Updated
May 31, 2017
Sponsor
University of Brasilia
Collaborators
Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministry of Science and Technology, Brazil, Ministry of Health, Brazil, Fundação Alfredo da Matta, Manaus, Brazil, Instituto de Dermatologia Dona Libania, Fortaleza, Brazil
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1. Study Identification

Unique Protocol Identification Number
NCT00669643
Brief Title
Uniform Multidrug Therapy Regimen for Leprosy Patients
Acronym
U-MDT
Official Title
Independent Study to Establish the Efficacy of the Six Doses Uniform MDT Regimen (U-MDT) for Leprosy Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
December 31, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Brasilia
Collaborators
Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministry of Science and Technology, Brazil, Ministry of Health, Brazil, Fundação Alfredo da Matta, Manaus, Brazil, Instituto de Dermatologia Dona Libania, Fortaleza, Brazil

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this randomized trial is to verify if leprosy patients, despite of their classification, can be treated with the same regimen without compromising patient cure and acceptability of the treatment. At present, patients classified as multibacillary leprosy are treated for 12 months with three drugs, and patients classified as paucibacillary leprosy are treated for 6 months with two drugs. The study is going to test a unified regimen for paucibacillary and multibacillary patients by treating leprosy patients with three drugs for 6 doses.
Detailed Description
In the past both the treatment of new leprosy patients and the classification criteria for treatment purposes have gone through major changes. At the moment, newly diagnosed leprosy patients are classified into PB and MB based on the number of lesions only. More than 5 lesions leads to a classification as MB patient and treatment for 12 months with MDT composed of three drugs, i.e. rifampicin, dapsone and clofazimine. One to 5 lesions leads to a classification as PB patient and treatment for 6 months with MDT composed of two drugs, i.e. rifampicin and dapsone. Despite all the favorable data from the point of view of practical application, this therapeutic regimen still presents some constraints, including the lengthy course of treatment. Especially in those situations where leprosy control is integrated into the general health services classification is a problem for the general health worker that has only received one or two days of training in leprosy. A uniform regimen for leprosy would simplify treatment in the field. Results from control programs and research projects have demonstrated that relapse rates after MDT are extremely low, approximately 0.2% annually among MB cases on the 24-dose regimen. The low relapse rates indicate that there was room to shorten the course of MDT to less than 24 monthly-supervised doses of rifampicin plus self-administered doses of dapsone and clofazimine. Although some papers have suggested that relapse rates after MDT may be significantly higher in MB patients with an initial bacterial index equals or bigger than 3, the present diagnostic universe of leprosy includes few such patients, and the total number of relapses caused by them would account for a minimal percentage of cases in a control program. Since 1998, a 12-month treatment course for MB leprosy is advised by WHO. The main problem when evaluating any new treatment regimen for leprosy, is that there are no good and reliable data available for the current treatment regimen: relapse rates have never been systematically determined and the same holds true for reaction and nerve function impairment rates, the major cause of the nerve damage that leads to handicaps and deformities in leprosy patients. Currently, WHO is exploring possibilities to introduce a short uniform treatment regimen for all types of leprosy patients called Uniform Multidrug Therapy (U-MDT), as a replacement for the present regular multidrug therapy (R-MDT). This U-MDT would consist of treatment of all patients for 6 months with a regimen consisting of three drugs: rifampicin, dapsone and clofazimine. The efficacy of this U-MDT is currently being studied in an open non-controlled treatment trial. Classification of patients is only done on clinical criteria: no skin smears or other lab tests are included. The diagnosis of relapse will rely on clinical diagnosis only. It will therefore not be possible to identify high-risk groups for relapse, such as highly skin smear positive patients. The objective of our study is to evaluate both the R-MDT and the U-MDT regimens in a randomised trial in order to: determine the efficacy of the current R-MDT regimen with regard to relapse rates and acceptability to the patient. determine the efficacy of the U-MDT regimen with regard to relapse rate and acceptability to the patient.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leprosy
Keywords
Leprosy, Communicable Diseases, Skin Diseases, Multidrug Therapy, MDT, Uniform Multidrug Therapy, U-MDT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
859 (Actual)

8. Arms, Groups, and Interventions

Arm Title
R-MDT PB
Arm Type
Active Comparator
Arm Description
R-MDT PB group: standard/regular treatment recommended by WHO - All patients presenting fewer than 6 skin lesions will receive the standard treatment regimen for paucibacillary patients as the intervention; Intervention - PB 6 doses of rifampicin and dapsone
Arm Title
U-MDT PB
Arm Type
Experimental
Arm Description
U-MDT PB group: a unified treatment for all patients - All patients presenting fewer than 6 lesions (WHO PB) will receive 6 doses of rifampicin, clofazimine and dapsone as the intervention; Intervention - PB 6 doses of rifampicin, clofazimine and dapsone
Arm Title
R-MDT MB
Arm Type
Experimental
Arm Description
R-MDT MB group: standard/regular treatment recommended by WHO - All patients presenting 6 skin or more lesions will receive the standard treatment regimen for multibacillary patients as the intervention; Intervention - MB 12 doses of rifampicin, clofazimine and dapsone
Arm Title
U-MDT MB
Arm Type
Experimental
Arm Description
U-MDT MB group: a unified treatment for all patients - All patients presenting 6 lesions or more (WHO MB) will receive 6 doses of rifampicin, clofazimine and dapsone as the intervention; Intervention - MB 6 doses of rifampicin, clofazimine and dapsone
Intervention Type
Drug
Intervention Name(s)
PB 6 doses - Rifampicin and Dapsone
Other Intervention Name(s)
PB 6 doses of 2 drugs
Intervention Description
Adult: 6 doses; 1 monthly supervised dose: 600 mg Rifampicin + 100 mg Dapsone; 27 days: p/day - 100 mg Dapsone; Children: 6 doses; 1 monthly supervised dose: 450 mg Rifampicin + 50 mg Dapsone; 27 days: p/day - 50 mg Dapsone
Intervention Type
Drug
Intervention Name(s)
PB 6 doses - Rifampicin, Clofazimine and Dapsone
Other Intervention Name(s)
PB 6 doses of 3 drugs
Intervention Description
Adult: 6 doses; 1 monthly supervised dose: 600 mg Rifampicin + 300 mg Clofazimine + 100 mg Dapsone; 27 days: p/day - 100 mg Dapsone + 50 mg Clofazimine; Children: 6 doses; 1 monthly supervised dose: Rifampicin 450 mg + 150 mg Clofazimine + 50 mg Dapsone; 27 days: p/day - 50 mg Dapsone + 25 mg Clofazimine
Intervention Type
Drug
Intervention Name(s)
MB 12 doses - Rifampicin, Clofazimine and Dapsone
Other Intervention Name(s)
MB 12 doses of 3 drugs
Intervention Description
Adult: 12 doses; 1 monthly supervised dose: 600 mg Rifampicin + 300 mg Clofazimine + 100 mg Dapsone; 27 days: p/day - 100 mg Dapsone + 50 mg Clofazimine; Children: 12 doses; 1 monthly supervised dose: Rifampicin 450 mg + 150 mg Clofazimine + 50 mg Dapsone; 27 days: p/day - 50 mg Dapsone + 25 mg Clofazimine
Intervention Type
Drug
Intervention Name(s)
MB 6 doses - Rifampicin, Clofazimine and Dapsone
Other Intervention Name(s)
MB 6 doses of 3 drugs
Intervention Description
Adult: 6 doses 1 monthly supervised dose: 600 mg Rifampicin + 300 mg Clofazimine + 100 mg Dapsone; 27 days: p/day - 100 mg Dapsone + 50 mg Clofazimine Children: 6 doses 1 monthly supervised dose: Rifampicin 450 mg + 150 mg Clofazimine + 50 mg Dapsone; 27 days: p/day - 50 mg Dapsone + 25 mg Clofazimine
Primary Outcome Measure Information:
Title
Relapse
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Type I Reaction - Reversal Reactions
Time Frame
6 years
Title
Type II Reaction - Erythema nodosum leprosum
Time Frame
6 years
Title
Neurological damage
Time Frame
6 years
Title
Neuritis
Time Frame
6 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All newly diagnosed leprosy cases with characteristic skin lesions, with or without systemic symptoms or confirmed by histopathological study previously untreated PB and MB leprosy patients. Never treated or patient treated more than five years ago Exclusion Criteria: Safety concerns: History of intolerance to one of the medications Lack of suitability for the trial: Absence of leprosy skin lesions Pure neural leprosy (PNL) Patient previously (defaulters and relapse) treated for leprosy less than 5 years ago Association with other serious diseases such as HIV/AIDS, Tuberculosis, Malaria, American Cutaneous leishmaniasis, Visceral Leishmaniasis, Lymphoma, Leukaemia, Immunosuppression, etc. Administrative reasons Patients who are not permanent residents of the area or who are unable to come to the clinic every month during their treatment and in the first half year (the intensive follow-up period) after their treatment. Patients who do not give informed consent or are not capable to give informed consent due to mental impairment. Patients with overt signs of AIDS because it is unlikely that we can follow them up for the whole study period. As we will not be testing patients for HIV positivity, HIV-infected leprosy patients can be included in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerson O Penna, MD, PhD
Organizational Affiliation
University of Brasilia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Samira Buhrer, PhD
Organizational Affiliation
Federal University of Goiás
Official's Role
Study Director
Facility Information:
Facility Name
Centro de Referência Nacional Alfredo da Matta - FUAM
City
Manaus
State/Province
Amazonas
ZIP/Postal Code
69.065-130
Country
Brazil
Facility Name
Centro de Referência Nacional Dona Libânia - CDERM
City
Fortaleza
State/Province
Ceará
ZIP/Postal Code
60.101-035
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data sharing was not previously requested to the Ethical Committee. Therefore, if there will be a request for it, new ethical approval must be obtained.
Citations:
PubMed Identifier
1474281
Citation
Becx-Bleumink M. Relapses among leprosy patients treated with multidrug therapy: experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia; practical difficulties with diagnosing relapses; operational procedures and criteria for diagnosing relapses. Int J Lepr Other Mycobact Dis. 1992 Sep;60(3):421-35.
Results Reference
background
PubMed Identifier
15081655
Citation
Britton WJ, Lockwood DN. Leprosy. Lancet. 2004 Apr 10;363(9416):1209-19. doi: 10.1016/S0140-6736(04)15952-7.
Results Reference
background
PubMed Identifier
12734239
Citation
Buhrer-Sekula S, Smits HL, Gussenhoven GC, van Leeuwen J, Amador S, Fujiwara T, Klatser PR, Oskam L. Simple and fast lateral flow test for classification of leprosy patients and identification of contacts with high risk of developing leprosy. J Clin Microbiol. 2003 May;41(5):1991-5. doi: 10.1128/JCM.41.5.1991-1995.2003.
Results Reference
background
PubMed Identifier
9207751
Citation
Dasananjali K, Schreuder PA, Pirayavaraporn C. A study on the effectiveness and safety of the WHO/MDT regimen in the northeast of Thailand; a prospective study, 1984-1996. Int J Lepr Other Mycobact Dis. 1997 Mar;65(1):28-36.
Results Reference
background
PubMed Identifier
7602214
Citation
Jamet P, Ji B. Relapse after long-term follow up of multibacillary patients treated by WHO multidrug regimen. Marchoux Chemotherapy Study Group. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):195-201.
Results Reference
background
PubMed Identifier
8690971
Citation
Jesudasan K, Vijayakumaran P, Manimozhi N, Jeyarajan T, Rao PS. Absence of relapse within 4 years among 34 multibacillary patients with high BIs treated for 2 years with MDT. Int J Lepr Other Mycobact Dis. 1996 Jun;64(2):133-5.
Results Reference
background
PubMed Identifier
9251596
Citation
Li HY, Hu LF, Wu PW, Luo JS, Liu XM. Fixed-duration multidrug therapy in multibacillary leprosy. Int J Lepr Other Mycobact Dis. 1997 Jun;65(2):230-7.
Results Reference
background
PubMed Identifier
9251597
Citation
Li HY, Hu LF, Huang WB, Liu GC, Yuan LC, Jin Z, Li X, Li JL, Yang ZM. Risk of relapse in leprosy after fixed-duration multidrug therapy. Int J Lepr Other Mycobact Dis. 1997 Jun;65(2):238-45.
Results Reference
background
PubMed Identifier
15798849
Citation
Lockwood DN, Suneetha S. Leprosy: too complex a disease for a simple elimination paradigm. Bull World Health Organ. 2005 Mar;83(3):230-5. Epub 2005 Mar 16.
Results Reference
background
PubMed Identifier
29867930
Citation
Hungria EM, Buhrer-Sekula S, Oliveira RM, Aderaldo LC, Pontes MAA, Cruz R, de Goncalves HS, Penna MLF, Penna GO, Stefani MMA. Mycobacterium leprae-Specific Antibodies in Multibacillary Leprosy Patients Decrease During and After Treatment With Either the Regular 12 Doses Multidrug Therapy (MDT) or the Uniform 6 Doses MDT. Front Immunol. 2018 May 14;9:915. doi: 10.3389/fimmu.2018.00915. eCollection 2018.
Results Reference
derived
PubMed Identifier
28704363
Citation
Penna GO, Buhrer-Sekula S, Kerr LRS, Stefani MMA, Rodrigues LC, de Araujo MG, Ramos AMC, de Andrade ARC, Costa MB, Rosa PS, Goncalves HS, Cruz R, Barreto ML, Pontes MAA, Penna MLF. Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): Results of an open label, randomized and controlled clinical trial, among multibacillary patients. PLoS Negl Trop Dis. 2017 Jul 13;11(7):e0005725. doi: 10.1371/journal.pntd.0005725. eCollection 2017 Jul.
Results Reference
derived
PubMed Identifier
28222139
Citation
Hungria EM, Buhrer-Sekula S, de Oliveira RM, Aderaldo LC, Pontes AA, Cruz R, Goncalves HS, Penna ML, Penna GO, Stefani MM. Leprosy reactions: The predictive value of Mycobacterium leprae-specific serology evaluated in a Brazilian cohort of leprosy patients (U-MDT/CT-BR). PLoS Negl Trop Dis. 2017 Feb 21;11(2):e0005396. doi: 10.1371/journal.pntd.0005396. eCollection 2017 Feb.
Results Reference
derived

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Uniform Multidrug Therapy Regimen for Leprosy Patients

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