A Pilot Randomized Clinical Trial: Oral Miltefosine and Pentavalent Antimonials Associated With Pentoxifylline for the Treatment of American Tegumentary Leishmaniasis

Abstract

IntroductionAmerican tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a post hoc analysis.MethodsA pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days.ResultsForty-three patients were included: 25 with ML and 18 with CL caused by L.(V.) braziliensis. AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058).ConclusionIn this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.

Clinical Diagnosis and Management of Mucosal Leishmaniasis in the Context of a Global Pandemic: A Case Report

“…However, efficacy rates are lower in the presence of ML, particularly in the “mucosal belt” of Peru, Bolivia, Paraguay, and southern Brazil, where ML is highly endemic. On average, the treatment failure rate is endorsed at around 40% in these highly endemic regions [ 9 , 11 ]. Miltefosine has demonstrated effective cure rates in ML caused by the Vianna subgenus in Brazil, Bolivia, Ecuador, and Argentina, with cure rates upwards of 70% [ 12 ].…”

“…This trial found no statistically significant difference between the two medications’ curative potential. However, a statistically significant increase in unwanted side effects from the sodium stibogluconate treatment was present, which may result in more frequent interruptions in treatment and subsequent prolongation of treatment duration [ 11 ]. Cochrane review of systemic therapies for cutaneous and mucocutaneous leishmaniasis concluded that meglumine antimoniate and miltefosine were the most likely systemic medications to have increased rates of cure, but that evidence was mostly low to moderate in quality [ 16 ].…”

Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments

“…Correlations were tested using Pearson’s r. Bootstrapping method was used to resample data and test correlation between cytokine levels and clinical parameters. Effect sizes of the differences between groups were calculated in the pilot clinical trial ( Martins et al., 2021 ). Using IBM ® SPSS Statistics, we calculated one-way multivariate analysis of variance (MANOVA) to compare age and group effects in the pilot clinical trial, and effect size r of Mann–Whitney was used to compare various quantitative variables at the end of the treatment.…”

Medication options in the treatment of cutaneous american tegumentary leishmaniasis

“…Dr. in Therapeutic Innovation Institution: Federal University of Northern Tocantins (UFNT) 2 Graduating in Medicine Institution: Federal University of Northern Tocantins (UFNT) 3 Graduating in Medicine Institution: Federal University of Northern Tocantins (UFNT) 4 Undergraduate student in Medicine 5 Undergraduate student in Medicine Institution: Centro Universitário Tocantinense Presidente Antônio Carlos (UNITPAC), Afya 6 Graduating in Medicine Institution: Centro Universitário dos Guararapes (UNIFG) 7 Graduating in Medicine Institution: Federal University of Northern Tocantins (UFNT) 8 Undergraduate student in Medicine Institution: Federal University of Northern Tocantins (UFNT) 9 Undergraduate student in Medicine Institution: Faculty of Higher Education of Amazônia Reunida (FESAR) 10 Post-Graduate in Systems Engineering Institution: Federal University of Northern Tocantins (UFNT) 11 Undergraduate student in Medicine Institution: Federal University of Northern Tocantins (UFNT)…”