Treatment of Cutaneous Leishmaniasis With a Combination of Miltefosine and Antimony

Study Overview
=================
Brief Summary
-----------------
Cutaneous leishmaniasis is endemic in the New World and, until recently, the standard treatment was pentavalent antimony. The cure rate for L panamensis in Colombia is 91%-93% and the cure rate in Bolivia is also 90%. Nevertheless, pentavalent antimonials have the disadvantages of multiple injections and mild-moderate clinical toxicity all of which are particularly unpleasant for a moderate clinical problem such as cutaneous leishmaniasis. The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and Bolivia (91 and 92% respectively). Side effects seen in patients with cutaneous disease that can be specifically attributed to the drug are nausea and vomiting of mild grade in approximately 25% of patients, and low-grade elevation of creatinine also in approximately 25% of patients. A further disadvantage of miltefosine is that regimens shorter than 4 weeks have not been evaluated for cutaneous disease. Combination therapy is now being used for many infectious diseases, such as tuberculosis, malaria, and HIV. Combination therapy offers the potential of preventing drug resistance, because organisms resistant to one of the drugs may be susceptible to the other drug; and also the potential to diminish drug therapy duration and thus side effects. These two potential benefits to some extent contradict each other: preventing resistance is best done if full courses of both drugs is used; diminishing therapy duration means using less than the full course of each drug. The optimum combination regimen is one in which sufficient amounts of both drugs are used to have high efficacy, yet the amounts are as low as possible to spare patients unnecessarily long courses of drug. In the present protocol, the combination of a half-course of miltefosine and a half-course of antimony will be evaluated for efficacy and tolerance. The combination of miltefosine and antimony is chosen because these are now the two standard agents in Bolivia, and in vitro the combination was additive to mildly synergistic against a standard leishmania strain.

Official Title
-----------------
Treatment of Bolivian Cutaneous Leishmaniasis With a Combination of Short Courses of Miltefosine and Antimony

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

Intervention / Treatment
-----------------
* Drug: Miltefosine and antimony
* Drug: Miltefosine alone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Parasitological confirmation at least 1 lesion must be ulcerative No specific antileishmanial therapy during the previous six months Exclusion Criteria: Concomitant diseases such as Tuberculosis, HIV, diabetes, renal failure, liver disease abnormalities CTC 2 in blood, liver, kidney test or EKG

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: Miltefosine and Antimony<br>Miltefosine 1,5 to 2,5 mg x k x d during 14 days simultaneously with meglumine antimoniate 20 mg x kg x d during 10 days | Drug: Miltefosine and antimony<br>* Short course (half of each drug) administered simultaneously<br>|
| Active Comparator: Miltefosine alone<br>Miltefosine 1,5 to 2,5 mg x kg x d during 14 days | Drug: Miltefosine alone<br>* short course (half)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healing of ulcers |  | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical findings and Laboratory parameters in normal ranges |  | 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Leishmaniasis, Miltefosine, Antimony, Therapy