Safety and Efficacy of Azithromycin to Treat Cutaneous Leishmaniasis

Study Overview
=================
Brief Summary
-----------------
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, pentavalent 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.

Detailed Description
-----------------
Included a new site (University Estadual de Montes Claros - UNIMONTES) in 7 June 2010. The site was included due the need to achieve more patients. The ANVISA (National Agency of Sanitary Surveillance) approved these site in March 2011 and the start of activities is planned for June 2011.

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

Conditions
-----------------
Cutaneous Leishmaniasis

Intervention / Treatment
-----------------
* Drug: Glucantime®
* Drug: Zithromax ®


Participation Criteria
=================
Eligibility Criteria
-----------------
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. No use of oral potentially antileishmanial drugs, or topics throughout the term of the current injury. Absence of disseminated leishmaniasis. Absence of mucosal involvement. Agreement to participate in the study and signed the informed consent. Exclusion Criteria: Diabetes mellitus, kidney diseases, liver or cardiac diseases, tuberculosis, malaria. Pregnancy lactating mothers 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-methylglucamine Abusive alcohol ingestion according to the CAGE questionnaire

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A - N- methyl glucamine<br>Glucantime® , max day of 1,215 mg | Drug: Glucantime®<br>* 15mg Sb+5/Kg/day, during 20 days. Maximum dose:15ml/day<br>* Other names: meglumine antimoniate;|
| Experimental: B - Azithromycin<br>Zithromax ® , one dose 500 mg | Drug: Zithromax ®<br>* Zithromax ®/ Pfizer, 500 mg - 1x day, during 20 days<br>* Other names: SELIMAX®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of clinically cured patients | A cure was defined as complete lesion healing and re-epithelialization without inflammatory infiltration and erythema until 90 days after the treatment ended. | at the third month after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with failure and cured | Proportion of cured patients at 1, 2, 3, 6, 9 and 12 follow-up after completion of treatment. Mean time to healing. | twelve months after treatment | 
| Occurrence of mucosal lesions after treatment | Proportion of patients with relapsed or mucosal lesion in 6 months, 9 and 12 follow-up after completion of treatment. | twelve months after treatment | 
| Proportion of patients presenting new lesions | Proportion of patients with new lesions at 1, 2, 3, 6, 9 and 12 follow-up after completion of treatment. | 1st 2nd 3rd 6th 12th month after treatment | 
| Proportion of adverse events on each treatment group | Proportion of patients clinical, electrocardiographic and laboratory adverse events. | 1st 2nd 3rd 6th 12th month after treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cutaneous leishmaniasis, azithromycin, N- methyl glucamine