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Randomized Controlled Trial
. 2021 Jul 1:11:700323.
doi: 10.3389/fcimb.2021.700323. eCollection 2021.

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

Sofia Sales Martins  1   2 , Daniel Holanda Barroso  2   3   4 , Bruna Côrtes Rodrigues  2   3 , Jorgeth de Oliveira Carneiro da Motta  2 , Gustavo Subtil Magalhães Freire  2 , Ledice Inácia de Araújo Pereira  5 , Patrícia Shu Kurisky  2   3 , Ciro Martins Gomes  2   3   4 , Raimunda Nonata Ribeiro Sampaio  1   2   3   4
Affiliations
Randomized Controlled Trial

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

Sofia Sales Martins et al. Front Cell Infect Microbiol. .

Abstract

Introduction: American 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.

Methods: A 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.

Results: Forty-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).

Conclusion: In 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.

Keywords: American tegumentary leishmaniasis; cutaneous leishmaniasis; miltefosine; mucosal leishmaniasis; pentavalent antimonial; pentoxifylline; randomized clinical trial.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram showing eligible patients, randomized patients and cure outcomes.
Figure 2
Figure 2
Top: wide septal perforation with infiltrated borders and granulomatous ulcerated aspect (pretreatment). Bottom: septal perforation with smooth borders without ulceration and with cicatricial aspect (90 days after treatment). Images obtained with nasofibroscopy and provided by Dr. Gustavo Subtil.
See this image and copyright information in PMC

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