Uniform Multidrug Therapy Regimen for Leprosy Patients

NCT00669643 | Completed Phase 4 DMC

• 1 other identifier: CNPq / DECIT 403293/2005-7
• Study Type: interventional
• Target: 859
• Locations: 1 country
• Sites: 2

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.

Conditions

Leprosy

Keywords

Leprosy; Communicable Diseases; Skin Diseases; Multidrug Therapy; MDT; Uniform Multidrug Therapy; U-MDT

Outcome Measures

Primary Outcomes (1)

• Relapse

  5 years

Secondary Outcomes (4)

• Type I Reaction - Reversal Reactions

  6 years

• Type II Reaction - Erythema nodosum leprosum

  6 years

• Neurological damage

  6 years

• Neuritis

  6 years

Study Arms (4)

R-MDT PB

ACTIVE COMPARATOR

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

Drug: PB 6 doses - Rifampicin and Dapsone

U-MDT PB

EXPERIMENTAL

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

Drug: PB 6 doses - Rifampicin, Clofazimine and Dapsone

R-MDT MB

EXPERIMENTAL

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

Drug: MB 12 doses - Rifampicin, Clofazimine and Dapsone

U-MDT MB

EXPERIMENTAL

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

Drug: MB 6 doses - Rifampicin, Clofazimine and Dapsone

Interventions

PB 6 doses - Rifampicin and Dapsone DRUG

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

Also known as: PB 6 doses of 2 drugs

R-MDT PB

PB 6 doses - Rifampicin, Clofazimine and Dapsone DRUG

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

Also known as: PB 6 doses of 3 drugs

U-MDT PB

MB 12 doses - Rifampicin, Clofazimine and Dapsone DRUG

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

Also known as: MB 12 doses of 3 drugs

R-MDT MB

MB 6 doses - Rifampicin, Clofazimine and Dapsone DRUG

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

Also known as: MB 6 doses of 3 drugs

U-MDT MB

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Brasilia: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Ministry of Science and Technology, Brazil: collaborator
• Ministry of Health, Brazil: collaborator
• Fundação Alfredo da Matta, Manaus, Brazil: collaborator
• Instituto de Dermatologia Dona Libania, Fortaleza, Brazil: collaborator

Study Sites (2)

Centro de Referência Nacional Alfredo da Matta - FUAM

Manaus, Amazonas, 69.065-130, Brazil

Location

Centro de Referência Nacional Dona Libânia - CDERM

Fortaleza, Ceará, 60.101-035, Brazil

Location

Related Publications (13)

• 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.

  PMID: 1474281 BACKGROUND

• Britton WJ, Lockwood DN. Leprosy. Lancet. 2004 Apr 10;363(9416):1209-19. doi: 10.1016/S0140-6736(04)15952-7.

  PMID: 15081655 BACKGROUND

• 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.

  PMID: 12734239 BACKGROUND

• 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.

  PMID: 9207751 BACKGROUND

• 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.

  PMID: 7602214 BACKGROUND

• 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.

  PMID: 8690971 BACKGROUND

• 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.

  PMID: 9251596 BACKGROUND

• 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.

  PMID: 9251597 BACKGROUND

• 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.

  PMID: 15798849 BACKGROUND

• Penna GO, Pontes MAA, Talhari S, Goncalves HS, Talhari C, Pessoa AS, Pedroza V, Buhrer-Sekula S, Stefani MMA, Penna MLF. Late relapses in leprosy patients in Brazil: 10-year post-trial of uniform multidrug therapy (U-MDT/CT-BR). Braz J Infect Dis. 2024 Mar-Apr;28(2):103745. doi: 10.1016/j.bjid.2024.103745. Epub 2024 Apr 30.

  PMID: 38697216 DERIVED

• 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.

  PMID: 29867930 DERIVED

• 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.

  PMID: 28704363 DERIVED

• 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.

  PMID: 28222139 DERIVED

MeSH Terms

Conditions

Leprosy; Communicable Diseases; Skin Diseases

Interventions

Rifampin; Dapsone; Clofazimine

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Sulfones; Sulfur Compounds; Organic Chemicals; Phenazines; Heterocyclic Compounds, 3-Ring

Study Officials

• Gerson O Penna, MD, PhD

  University of Brasilia

  PRINCIPAL INVESTIGATOR

• Samira Buhrer, PhD

  Federal University of Goiás

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 30, 2008
• Study Start: February 1, 2007
• Primary Completion: September 1, 2012
• Study Completion: December 31, 2016
• Last Updated: June 1, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2)