Clinical trial NCT00669643: Uniform Multidrug Therapy Regimen for Leprosy Patients
Official title: Independent Study to Establish the Efficacy of the Six Doses Uniform MDT Regimen (U-MDT) for Leprosy Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Leprosy
Keywords: Leprosy
Communicable Diseases
Skin Diseases
Multidrug Therapy
MDT
Uniform Multidrug Therapy
U-MDT
Lead sponsor: University of Brasilia
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
name: Ministry of Science and Technology, Brazil
name: Ministry of Health, Brazil
name: Fundação Alfredo da Matta, Manaus, Brazil
name: Instituto de Dermatologia Dona Libania, Fortaleza, Brazil
First posted: 2008-04-30
Enrollment: 859
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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.

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.

Primary outcomes:
measure: Relapse
timeFrame: 5 years
Secondary outcomes:
measure: Type I Reaction - Reversal Reactions
timeFrame: 6 years
measure: Type II Reaction - Erythema nodosum leprosum
timeFrame: 6 years
measure: Neurological damage
timeFrame: 6 years
measure: Neuritis
timeFrame: 6 years
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Centro de Referência Nacional Alfredo da Matta - FUAM
state: Amazonas
city: Fortaleza
country: Brazil
facility: Centro de Referência Nacional Dona Libânia - CDERM
state: Ceará
Study officials:
affiliation: University of Brasilia
name: Gerson O Penna, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal University of Goiás
name: Samira Buhrer, PhD
role: STUDY_DIRECTOR
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