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

This study is ongoing, but not recruiting participants.
Sponsor:
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
Information provided by (Responsible Party):
Gerson Oliveira Penna, University of Brasilia
ClinicalTrials.gov Identifier:
NCT00669643
First received: April 24, 2008
Last updated: April 2, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Leprosy
Drug: Rifampicin and Dapsone
Drug: Rifampicin, Clofazimine and Dapsone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Brasilia:

Primary Outcome Measures:
  • Relapse [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Type I Reaction - Reversal Reactions [ Time Frame: 6 years ] [ Designated as safety issue: No ]
  • Type II Reaction - Erythema nodosum leprosum [ Time Frame: 6 years ] [ Designated as safety issue: No ]
  • Neurological damage [ Time Frame: 6 years ] [ Designated as safety issue: No ]
  • Neuritis [ Time Frame: 6 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 2122
Study Start Date: February 2007
Estimated Study Completion Date: October 2016
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 6 months treatment with rifampicin and dapsone
Drug: 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

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 months treatment with rifampicin, clofazimine and dapsone
Drug: 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

Active Comparator: 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 12 months treatment with rifampicin, clofazimine and dapsone
Drug: 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

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 months treatment with rifampicin, clofazimine and dapsone
Drug: 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


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

Ages Eligible for Study:   6 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00669643

Locations
Brazil
Centro de Referência Nacional Alfredo da Matta - FUAM
Manaus, Amazonas, Brazil, 69.065-130
Centro de Referência Nacional Dona Libânia - CDERM
Fortaleza, Ceará, Brazil, 60.101-035
Sponsors and Collaborators
University of Brasilia
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
Investigators
Principal Investigator: Gerson O Penna, MD, PhD University of Brasília
Study Director: Samira Buhrer, PhD Federal University of Goiás
  More Information

Publications:

Responsible Party: Gerson Oliveira Penna, Dr., University of Brasilia
ClinicalTrials.gov Identifier: NCT00669643     History of Changes
Other Study ID Numbers: CNPq / DECIT 403293/2005-7
Study First Received: April 24, 2008
Last Updated: April 2, 2013
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Brasilia:
Leprosy
Communicable Diseases
Skin Diseases
Multidrug Therapy
MDT
Uniform Multidrug Therapy
U-MDT

Additional relevant MeSH terms:
Leprosy
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Clofazimine
Dapsone
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antitubercular
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Antitubercular Agents
Enzyme Inhibitors
Folic Acid Antagonists
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014