Safety and Efficacy of Azithromycin to Treat Cutaneous Leishmaniasis

Official Title: “Open Label Randomized Study to Assess Safety and Efficacy of Azithromycin Versus Meglumine Antimoniate to Treat Cutaneous Leishmaniasis”

The adequate treatment of the American tegumentary leishmaniasis is crucial since the disease, differently from the caused by the Old World species, is painful and not self-healing and may lead to the disfiguring mucosal involvement. So far, pentavalents antimony compounds have been considered the treatment of choice for cutaneous leishmaniasis (CL), however, these drugs present high frequency of side effects and important disadvantages as parenteral administration and need for careful renal and cardiac monitoring. Azithromycin is a macrolide antibiotic, non-expensive, largely commercially available that has shown in-vitro and in vivo activity against different species of Leishmania.

The main objective of this study is to evaluate the efficacy and safety of oral azithromycin for the treatment of CL. The efficacy of oral treatment of azithromycin 500 mg/day for 20 days is going to be compared with the standard treatment of intramuscular injections of 20 mg/Kg/day of pentavalent antimonials (Glucantime®) for 20 days in patients with CL from two endemic regions of Brazil: the metropolitan region of Belo Horizonte and Montes Claros (MG)in the southeast Brazil and in Corte de Pedras (Bahia), Northeastern Brazil. The patients follow up lasts for 12 months.

Included a new site (University Estadual de Montes Claros - UNIMONTES) in 7 June 2010. The site was included due the need to achieve more patientes. The ANVISA aproved these site in March 2011 and the start of activities is planned for June 2011.

Intervention(s) in this Clinical Trial

• Drug: N-metil glucamine
  • N-metil glucamine (Glucantime®-Aventis) 15mg Sb+5/Kg/day, during 20 days. Maximum dose: 15ml/day
• Drug: Azithromycin
  • Azithromycin (Zitromax®/ Pfizer) 500 mg per os 1x day, during 20 days

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • N-metil glucamine
• Experimental: B
  • Azithromycin

Primary Measures

• Proportion of clinically cured patients
  • Time Frame: at the third month after treatment
    Safety Issue?: No

Secondary Measures

• Proportion of patients with failure
  • Time Frame: twelve months after treatment
    Safety Issue?: No
• Occurrence of mucosal lesions after treatment
  • Time Frame: twelve months after treatment
    Safety Issue?: No
• Proportion of patients presenting new lesions
  • Time Frame: 1st 2nd 3rd 6th 12th month after treatment
    Safety Issue?: No
• Proportion of adverse events on each treatment group
  • Time Frame: 1st 2nd 3rd 6th 12th month after treatment.
    Safety Issue?: Yes

Inclusion Criteria:

• Patients older than 14 and younger than 65 years old
• Skin lesions with clinical suggestion of cutaneous leishmaniasis and positive leishmanin skin test(Montenegro test)or parasitological (direct observation of leishmania amastigotes, leishmania in vitro culture from aspirates, histopathological) and molecular(Polymerase Chain Reaction - PCR)samples
• Agreement to participate in the study and signed the informed consent

Exclusion Criteria:

• Diabetes mellitus, kidney diseases, liver or cardiac diseases, tuberculosis, malaria.
• Pregnancy
• Breast feeding
• Cutaneous lesion with bacterial infection for which antibiotics need to be prescribed
• More than six cutaneous lesions
• Previous history of cutaneous or mucosal leishmaniasis
• Use of drugs with potential pharmacological interactions with antimonials as anti-arrhythmic or tricycle anti-depressives
• Previous intolerance to azithromycin or other macrolides or N-metilglucamine
• Abusive alcohol ingestion according to the CAGE questionnaire

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 14 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Oswaldo Cruz Foundation Other

Overall Clinical Trial Officials and Contacts

Ana Rabello, MD PhD Principal Investigator Oswaldo Cruz Foundation  

Overall Contact: Ana Rabello, MD, PhD 55-31-3349-7708 ana@cpqrr.fiocruz.br

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00682656

Study ID Number: CEPSH/CPqRR 21/2006

ClinicalTrials.gov Identifier: NCT00682656

Health Authority: Brazil: National Health Surveillance Agency