Uniform Multidrug Therapy Regimen for Leprosy Patients

Leprosy Clinical Trial

— U-MDT  

Official title:

Independent Study to Establish the Efficacy of the Six Doses Uniform MDT Regimen (U-MDT) for Leprosy Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00669643
• Other study ID #: CNPq / DECIT 403293/2005-7
• Status: Completed
• Phase: Phase 4
• First received: April 24, 2008
• Last updated: May 31, 2017
• Start date: February 2007
• Est. completion date: December 31, 2016

Study information

• Verified date: May 2017
• Source: University of Brasilia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

1. determine the efficacy of the current R-MDT regimen with regard to relapse rates and acceptability to the patient.

2. determine the efficacy of the U-MDT regimen with regard to relapse rate and acceptability to the patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 859
• Est. completion date: December 31, 2016
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leprosy

Intervention

Drug:
• PB 6 doses - Rifampicin and Dapsone
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
• PB 6 doses - Rifampicin, Clofazimine and Dapsone
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
• MB 12 doses - Rifampicin, Clofazimine and Dapsone
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
• MB 6 doses - Rifampicin, Clofazimine and Dapsone
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

Locations

Country	Name	City	State
Brazil	Centro de Referência Nacional Dona Libânia - CDERM	Fortaleza	Ceará
Brazil	Centro de Referência Nacional Alfredo da Matta - FUAM	Manaus	Amazonas

Sponsors (6)

Lead Sponsor	Collaborator
University of Brasilia	Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Alfredo da Matta, Manaus, Brazil, Instituto de Dermatologia Dona Libania, Fortaleza, Brazil, Ministry of Health, Brazil, Ministry of Science and Technology, Brazil

Country where clinical trial is conducted

Brazil, 

References & Publications (9)

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. Review. — View Citation

Britton WJ, Lockwood DN. Leprosy. Lancet. 2004 Apr 10;363(9416):1209-19. Review. — View Citation

Bührer-Sékula 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse		5 years
Secondary	Type I Reaction - Reversal Reactions		6 years
Secondary	Type II Reaction - Erythema nodosum leprosum		6 years
Secondary	Neurological damage		6 years
Secondary	Neuritis		6 years