| Chrusciak-Talhari 2011 (Brazil) [73]
|
Open label randomized trial at a dermatology outpatient clinic |
Patients having clinical diagnosis of CL; illness duration of less than 3 months; visualization of Leishmania amastigotes on Giemsa; no previous Leishmania treatment. Exclusion criteria HIV patients and pregnant women. Identification of Leishmania Viannia by PCR-RFLP on skin biopsies from enrolled patients. L. guyanensis, L. braziliensis and L. lainsoni were identified. |
Miltefosine administered orally at the total target daily dosage of 2.5 mg/kg of body weight (maximum daily dose of 150 mg) for 28 consecutive days. Glucantime administered intravenously at a dose of 20 mg Sb +5/kg/day (age group 13–65 y/o) and 15 mg Sb +5/kg/day (age group 2–12 y/o) for 20 consecutive days (maximum daily dose of 3 ampoules), |
Cure rate at 1,2,4,6 months; adverse events |
| Lopez 2012 (Colombia) [71]
|
Open label randomized trial at five military health clinics in Colombia |
Positive parasitologic diagnosis of leishmaniasis; no previous treatment for this parasitic infection; laboratory exams including renal, hepatic and hematologic testing and; voluntary agreement to participate. Excluded: patients with chronic concomitant diseases; lesions compromising the mucosa; presence of 10 or more cutaneous lesions with a negative Montenegro test; cutaneous lesions located less than 2 cm from the nasal or oral mucosa, eyes or near the anal or urogenital orifices. Identificacion of Leishmania type was done from histologic samples using PCR-RFLP. L. panamensis and L. brazililensis were identified. |
Thermotherapy: single session, active borders and peripheral area of the lesions. Each thermal application was at 50°C and lasted for 30 seconds; the number of applications depended on the size of the lesion. Fusidic acid was applied over the lesions for 10 days. Meglumine antimoniate (Glucantime®) was administered intramuscularly under medical supervision at a dose of 20 mg Sb5/kg/day for 20 days. Meglumine antimoniate was provided as rescue therapy for all patients |
Cure rate at 6 months. “Complete reepithelialization of all ulcers and complete loss of induration up to three months after the end of treatment”; recurrence; reinfection; adverse events |
| López-Jaramillo 2010 (Colombia) [81]
|
Double-blind, randomized clinical trial at local hospitals in Santander and Tolima, Colombia |
Inclusion criteria: >10 years of age; a parasitological diagnosis of CL with demonstration of Leishmania amastigotes on smears or promastigotes in culture. Exclusion criteria: any history of anti- Leishmania therapy in the last 3 months, presence of >5 lesions, or presence of lesions in the perimeter (<2 cms) of mucosal areas, eyes, nose, mouth, or genitals. CL caused by L. panamensis. |
Meglumine antimoniate (Glucantime) 20 mg/kg/day plus a placebo patch for 20 days. Intramuscular placebo (5–20 cc/day), and an active Nitric Oxide releasing patch for 20 days. |
Cure rate at 90 days; relapse; reinfection; adverse events |
| Machado 2010 (Brazil) [74]
|
Open label randomized trial at the health post of Corte de Pedra, Bahia, Brazil. |
Inclusion criteria: presence of a typical ulcerated lesion and a positive Montenegro intradermal skin test in a subject living in the endemic area; age 2–65 years; a maximum of 5 ulcers with no more than 2 body regions involved; lesion size between 10 and 50 mm in a single dimension; a period of less than 90 days from the onset of the first ulcer. Punch biopsy to obtain material for Leishmania culture and PCR. Exclusion criteria: prior history of CL or antimony use, evidence of mucosal or disseminated disease, pregnancy or breastfeeding; HIV or any systemic severe disease. L. (V.) braziliensis was identified. |
Miltefosine orally at the total target daily dosage of 2.5 mg/kg of body weight (maximum daily dose of 150 mg) for 28 consecutive days. Pentavalent antimony intravenously at a dose of 20 mg Sbv/kg/day for 20 consecutive days (maximum daily dose of 3 ampoules or 1215 mg/Sbv). |
Cure rate at 2 weeks, 1, 2, 4 and 6 months; relapses; adverse events |
| Miranda-Verastegui 2009 (Peru) [76]
|
Randomized double-blind clinical trial. at the Instituto de Medicina Tropical ‘Alexander von Humbolt’–Hospital Nacional Cayetano Heredia in Lima and Cusco, Peru |
Inclusion criteria: presence of an active ulcerative cutaneous Leishmania lesion, and a positive identification of the parasite from the lesion. (smear microscopy, culture, or PCR); 5–65 years; duration of disease more than 4 weeks; no prior therapy with anti-Leishmania drugs; Exclusion: pregnancy; lesion(s) >2,500 mm2; more than 6 cutaneous lesions; mucosal lesion; any acute or chronic illness; concomitant infection; others. CL caused by L. peruviana, L. guyanensis, L. braziliensis
|
Imiquimod or placebo vehicle cream three times per week for a total of 9 applications during the 20-day course of treatment with pentavalent antimony. Pentavalent antimony intravenously 20 mg sodium stibogluconate per kg body weight/day for 20 consecutive days to all participants. |
Cure rate at 1, 2, 3, 6, 9, 12 months; local side effects. |
| Neves 2011 (Brazil) [69]
|
Open-label, controlled, randomized, multicenter at the Tropical Medicine Foundation of Amazonas |
Inclusion criteria: weight: greater than 8 kg; clinical findings compatible with CL and positive direct examination (by smear) for Leishmania; disease duration: between one and three months of evolution; number of lesions: a maximum of six lesions; presence of at least one ulcerated lesion; lack of mucosal involvement and no history, confirmed or not, of cutaneous leishmanial lesion. Exclusion criteria: Prior treatment with pentavalent antimonials or leishmanicidal drugs in the last six months; evidence of cardiac abnormalities; concomitant tuberculosis, leprosy, cancer, diabetes mellitus or other serious illness; Uncontrolled hypertension; or peripheral vascular involvement; pregnancy; others. CL caused by L. guyanensis, and L braziliensis was identified. |
Pentavalent antimonial at 15 mg/kg/day for 20 days, administered intravenously (IV) or intramuscularly (IM). Pentamidine - three doses of 4 mg/kg were administered every 72 hours via deep intramuscular injection with the patient in a supine position. The maximum dose was 300 mg/dose. Amphotericin B –1 mg/kg/day IV for 20 days. On the first two days, the maximum low dose was (0.5 mg/kg/day). These first two doses were not considered in the calculation of the twenty days of treatment. Rescue treatment: pentamidine isethionate, |
Cure rate at 30, 60 and 180 days; rescue treatment; adverse events. |
| Newlove 2011 (Brazil) [72]
|
Double-Blind, Placebo-Controlled Trial at the state of Bahia, Brazil |
Inclusion criteria: Cutaneous leishmaniasis diagnosed by a typical ulcer and a positive intradermal antigen test; 13–50 years; a maximum of three ulcers; lesion diameter 5–50 mm; and a period of 15 to 60 days from the onset of the ulcer. Exclusion criteria: prior history of CL or Sb v or helminths use; mucosal or disseminated disease; pregnancy; others. CL caused by L. braziliensis. |
Albendazole (400 mg), ivermectin (200 µg/kg), and praziquantel (50 mg/kg) in an oral formulation at Days 0 and 30 and placebo at Day 60. The control group received placebo. These patients were also treated with the appropriate oral antihelminthic based on parasitological assay results on the 60-day visit. All patients were treated with intravenous pentavalent antimony (Glucantime) at 20 mg/kg/. |
Cure rate at 90 days; time to cure; adverse events |
| Rubiano 2012 (Colombia) [70]
|
Multicenter, open-label, randomized clinical trial at conducted in 3 geographic locations in Colombia. |
Inclusion criteria: children aged 2–12 years with parasitologically confirmed cutaneous leishmaniasis. Exclusion criteria were weight <10 kg, mucocutaneous disease, use of anti-Leishmania medications during the month prior to diagnosis, medical history of cardiac, renal, or hepatic disease, menarche, and others. L. panamensis and L. guyanensis predominated; few L. braziliensis.
|
Meglumine antimoniate (81 mg Sb/mL) at 20 mg Sb/kg/d intramuscular for 20 consecutive days. Miltefosine (10 mg miltefosine/capsule) at 1.5–2.5 mg/kg/d by mouth during 28 consecutive days, divided into 2 or 3 daily doses. |
Cure rate Therapeutic failure during 26 weeks. Parasitologic response; adverse events. |
| Soto 2008 (Bolivia) [77]
|
Open-label, randomized clinical trial in Palos Blancos, Bolivia |
Inclusion criteria: a skin ulcer confirmed to be caused by leishmania by visualization of parasites in lesion material by Giemsa staining; >12 years of age Exclusion criteria: mucosal disease or anti-leishmanial therapy for at least 6 months; significant concomitant disease; pregnancy or lactation. L. panamensis, L. guyanensis and L. braziliensis were identified. |
Oral miltefosine 2.5 mg/kg/d for 28 days. Intramuscular pentavalent antimony (glucantime, 20 mg/kg/d) for 20 days. |
Cure rate at 1, 3, and 6 months; adverse events |
| Velez 2010 (Colombia) [75]
|
Randomized, open-label phase III clinical in five military health establishments located in central, northeast, and southern Colombia |
Inclusion criteria: confirmed parasitological diagnosis of leishmaniasis; received no treatment of the current infection during the past 6 weeks; normal renal, hepatic, pancreatic, and hematological functions. Exclusion criteria: serious concomitant illnesses; lesions with mucosal involvement; Disseminated cutaneous leishmaniasis (presence of 10 or more cutaneous lesions and a negative Montenegro skin test). L. panamensis and L. brazililensis were identified. |
Miltefosine 50 mg orally three times per day for 28 days. Meglumine antimoniate intramuscularly at a dose of 20 mg/kg body weight per day for 20 days |
Cure rate 6 weeks, 3 months, and 6 months after; failure; recurrence; reinfection Rescue therapy |
