Comparison of Low and High Antimonial Dosage in American Cutaneous Leishmaniasis

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Oswaldo Cruz Foundation
Sponsor:
Collaborators:
Rio de Janeiro State Research Supporting Foundation (FAPERJ)
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Information provided by (Responsible Party):
ASchubach, Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier:
NCT01301924
First received: February 20, 2011
Last updated: September 18, 2013
Last verified: September 2013
  Purpose

"Phase III clinical trial for American tegumentary leishmaniasis. Equivalence between the standard and alternative schemes with meglumine antimoniate" has begun in October 2008 at the Laboratory of Leishmaniasis Surveillance at Evandro Chagas Clinical Research Institute (IPEC), FIOCRUZ, aiming to compare efficacy and safety of the standard recommended schedule with alternative regimens of meglumine antimoniate in the treatment of American tegumentary leishmaniasis (ATL). It is a study with blind evaluation by the doctors and the responsible for statistical analysis. Patients diagnosed with ATL, eligible for the trial are randomly allocated into one of the schemes with meglumine antimoniate and monitored before, during and after it. There is no single regimen applicable to all forms of leishmaniasis around the world. Therapeutic regimens applied to treat people living in other geographic areas result in mixed outcomes. Ideally, the most appropriate regimens should be established for each endemic area, based on its efficacy, toxicity, difficulties of administration and cost. Given the problems and limitations of the use of pentavalent antimonials (Sb5+) at 20 mg Sb5+ / kg / day, less toxic alternative regimens, i.e. 5mg Sb5+/kg/day and intralesional therapy, deserve to be better evaluated. The treatment of ATL must heal skin lesions and prevent late mucosal lesion development. The indication of high doses of Sb5+ is based on the evidence that there could be induction of resistance with use of subdoses. However, clinical studies with extended follow-up in Rio de Janeiro have suggested that regular low doses (5mg Sb5+ / kg / day) in a systemic way as well as intralesional therapy with meglumine antimoniate may constitute effective schemes, achieving cure rates similar to higher doses, with lower toxicity, ease of implementation and lower cost. Published studies on efficacy and safety of alternative schemes with meglumine antimoniate failed to provide conclusive results, for various methodological biases. The need to compare the effectiveness and safety between treatment schemes with meglumine antimoniate currently recommended in Brazil for the treatment of ATL and alternative schemes with low doses of antimony is the motive for this study in Rio de Janeiro.


Condition Intervention Phase
Cutaneous Leishmaniasis
Drug: Meglumine antimoniate
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Caregiver)
Primary Purpose: Treatment
Official Title: Phase III Clinical Trial for American Tegumentary Leishmaniasis: Equivalence Between the Standard and Alternative Schemes With Meglumine Antimoniate

Resource links provided by NLM:


Further study details as provided by Oswaldo Cruz Foundation:

Primary Outcome Measures:
  • Effectiveness of meglumine antimoniate treatment [ Time Frame: 6 years ] [ Designated as safety issue: No ]
    To compare the effectiveness of meglumine antimoniate at a dose of 5 mg or 20 mg Sb5+ / kg / day in the treatment of patients with cutaneous leishmaniasis.


Secondary Outcome Measures:
  • Safety of meglumine antimoniate treatment [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]
    To compare the safety of meglumine antimoniate at a dose of 5 mg or 20 mg Sb5+ / kg / day in the treatment of patients with cutaneous leishmaniasis.


Estimated Enrollment: 264
Study Start Date: October 2008
Estimated Study Completion Date: July 2016
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: High dose
High dose: 20 days of 20 mg/kg/day meglumine antimoniate
Drug: Meglumine antimoniate

Meglumine antimoniate is stored and ministered under actual conditions employed by health services in Brazil. Each patient will be included in one of the treatment groups with meglumine antimoniate IM:

High dose: 20 days of 20 mg/kg/day antimoniate meglumine. Low dose: 30 days of 5 mg/kg/day antimoniate meglumine.

Other Names:
  • High dose
  • Low dose
Experimental: Low dose
Low dose: 30 days of 5 mg/kg/day meglumine antimoniate
Drug: Meglumine antimoniate

Meglumine antimoniate is stored and ministered under actual conditions employed by health services in Brazil. Each patient will be included in one of the treatment groups with meglumine antimoniate IM:

High dose: 20 days of 20 mg/kg/day antimoniate meglumine. Low dose: 30 days of 5 mg/kg/day antimoniate meglumine.

Other Names:
  • High dose
  • Low dose

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria.

Inclusion criteria:

  1. Cutaneous leishmaniasis with parasitological diagnosis by one or more of the following methods: direct examination (scraping or imprint), histopathology, culture, immunohistochemistry, or PCR.
  2. History of exposure in an endemic area of Rio de Janeiro
  3. Absence of prior treatment with meglumine antimoniate

Exclusion criteria:

  1. women who do not use contraceptives or do it inadequately
  2. pregnant
  3. under 13
  4. prior treatment with meglumine antimoniate
  5. use of immunosuppressive therapy (steroids, cancer chemotherapy) or medicines for tuberculosis or leprosy.
  6. presence of changes in baseline clinical adverse effect level equivalent to> G3
  7. presence of changes in baseline laboratory adverse effect level equivalent to> G2
  8. presence of baseline electrocardiographic changes equivalent to an adverse effect level> G4 and / or baseline QTc> 0.46 ms (equivalent to AS level G1).
  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: NCT01301924

Contacts
Contact: Armando O Schubach, MD., PhD (55)(21)38659673 armando.schubach@ipec.fiocruz.br
Contact: Maria Inês F Pimentel, MD., PhD (55)(21)38659541 vigileish@ipec.fiocruz.br

Locations
Brazil
Oswaldo Cruz Foundation - IPEC/FIOCRUZ Recruiting
Rio de Janeiro, Brazil
Sponsors and Collaborators
Oswaldo Cruz Foundation
Rio de Janeiro State Research Supporting Foundation (FAPERJ)
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Investigators
Study Director: Armando O. Schubach, MD, PhD IPEC/FIOCRUZ
  More Information

Publications:

Responsible Party: ASchubach, Senior Researcher, Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier: NCT01301924     History of Changes
Other Study ID Numbers: low dosage CL
Study First Received: February 20, 2011
Last Updated: September 18, 2013
Health Authority: Brazil: Ministry of Health
Brazil: Ethics Committee

Keywords provided by Oswaldo Cruz Foundation:
Leishmaniasis Cutaneous
Leishmania braziliensis
Meglumine Antimoniate
Treatment Effectiveness
Controlled Clinical Trials, Randomized

Additional relevant MeSH terms:
Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Meglumine antimoniate
Meglumine
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Contrast Media
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on October 19, 2014