U-MDT: Uniform Multidrug Therapy Regimen for Leprosy Patients

Sponsor

University of Brasilia (Other)

Overall Status

Completed

CT.gov ID

NCT00669643

Collaborator

Conselho Nacional de Desenvolvimento Científico e Tecnológico (Other), Ministry of Science and Technology, Brazil (Other), Ministry of Health, Brazil (Other), Fundação Alfredo da Matta, Manaus, Brazil (Other), Instituto de Dermatologia Dona Libania, Fortaleza, Brazil (Other)

859

Enrollment

Locations

Arms

119

Duration (Months)

429.5

Patients Per Site

3.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Leprosy	Drug: PB 6 doses - Rifampicin and Dapsone Drug: PB 6 doses - Rifampicin, Clofazimine and Dapsone Drug: MB 12 doses - Rifampicin, Clofazimine and Dapsone Drug: MB 6 doses - Rifampicin, Clofazimine and Dapsone	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

859 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Dec 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: R-MDT PB 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 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 Other Names: PB 6 doses of 2 drugs
Experimental: U-MDT PB 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 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 Other Names: PB 6 doses of 3 drugs
Experimental: R-MDT MB 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 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 Other Names: MB 12 doses of 3 drugs
Experimental: U-MDT MB 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 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 Other Names: MB 6 doses of 3 drugs

Outcome Measures

Primary Outcome Measures

Relapse [5 years]

Secondary Outcome Measures

Type I Reaction - Reversal Reactions [6 years]
Type II Reaction - Erythema nodosum leprosum [6 years]
Neurological damage [6 years]
Neuritis [6 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centro de Referência Nacional Alfredo da Matta - FUAM	Manaus	Amazonas	Brazil	69.065-130
2	Centro de Referência Nacional Dona Libânia - CDERM	Fortaleza	Ceará	Brazil	60.101-035