Randomized, phase 1/2, double-blind pioglitazone repositioning trial combined with antifungals for the treatment of cryptococcal meningitis – PIO study

• Autor(a) principal: Ludmila Gouveia-Eufrasio
• Data de Publicação: 2021
• Outros Autores: Noelly Queiroz Ribeiro, Julliana Ribeiro Alves Santos, Marliete Carvalho da Costa, Elúzia Castro Peres Emídio, Gustavo José Cota de Freitas, Paulo Henrique Fonseca do Carmo, Bárbara Alves Miranda, João Carlos Maia Dornelas de Oliveira, Lívia Mara Vitorino da Silva, Victor Augusto Teixeira Leocádio, Vanessa Caroline Randi Magalhães, Indiara Penido, Leonardo Soares Pereira, Lívia Frota Rabelo, Flávio Augusto de Almeida Faria, Maria Rita Teixeira Dutra, Maíra Aspahan, Ludmila de Paula, Dirce Inês da Silva, Márcia Gregory Tavares Melo, Virginia Antunes de Andrade Zambelli, André Augusto Gomes Faraco, Isabela da Costa César, Glauciene Prado Alves, Lívia Fulgêncio da Cunha Melo, Nalu Teixeira de Aguiar Peres, Daniel de Assis Santos
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://doi.org/10.1016/j.conctc.2021.100745; http://hdl.handle.net/1843/56345; https://orcid.org/0000-0001-6918-1186; https://orcid.org/0000-0003-0381-9225; https://orcid.org/0000-0003-3186-885X; https://orcid.org/0000-0003-0035-6261; https://orcid.org/0000-0002-5426-0655; https://orcid.org/0000-0002-2344-6158; https://orcid.org/0000-0002-1108-5666
• topic: Drug repositioning; Clinical trial; Pioglitazone; Cryptococcosis; PIO-STUDY; Reposicionamento de medicamentos; Ensaio clínico; Pioglitazona; Criptococose

Background: Cryptococcosis affects more than 220,000 patients/year, with high mortality even when the standard treatment [amphotericin B (AMB), 5-flucytosin (5-FC) and fluconazole] is used. AMB presents high toxicity and 5-FC is not currently available in Brazil. In a pre-clinical study, pioglitazone (PIO - an antidiabetic drug) decreased AMB toxicity and lead to an increased mice survival, reduced morbidity and fungal burden in brain and lungs. The aim of this trial is to evaluate the efficacy and safety of PIO combined with standard antifungal treatment for human cryptococcosis. Methods: A phase 1/2, randomized, double blind, placebo-controlled trial will be performed with patients from Belo Horizonte, Brazil. They will be divided into three groups (placebo, PIO 15 mg/day or PIO 45 mg/day) and will receive an additional pill during the induction phase of cryptococcosis’ treatment. Our hypothesis is that treated patients will have increased survival, so the primary outcome will be the mortality rate. Patients will be monitored for survival, side effects, fungal burden and inflammatory mediators in blood and cerebrospinal fluid. The follow up will occur for up 60 days. Conclusions: We expect that PIO will be an adequate adjuvant to the standard cryptococcosis’ treatment.