Gouveia-Eufrasio Ludmila, Ribeiro Noelly Queiroz, Santos Julliana Ribeiro Alves, da Costa Marliete Carvalho, Emídio Elúzia Castro Peres, de Freitas Gustavo José Cota, do Carmo Paulo Henrique Fonseca, Miranda Bárbara Alves, de Oliveira João Carlos Maia Dornelas, da Silva Lívia Mara Vitorino, Teixeira Leocádio Victor Augusto, Randi Magalhães Vanessa Caroline, Penido Indiara, Pereira Leonardo Soares, Rabelo Lívia Frota, de Almeida Faria Flávio Augusto, Teixeira Dutra Maria Rita, Aspahan Maíra, de Paula Ludmila, da Silva Dirce Inês, Tavares Melo Márcia Gregory, de Andrade Zambelli Virginia Antunes, Gomes Faraco André Augusto, da Costa César Isabela, Alves Glauciene Prado, da Cunha Melo Lívia Fulgêncio, de Aguiar Peres Nalu Teixeira, Santos Daniel Assis
Mycology Lab, Departamento de Microbiolgia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Environmental Microbiology Lab, Universidade Ceuma, São Luís, Maranhão, Brazil.
Contemp Clin Trials Commun. 2021 Feb 10;22:100745. doi: 10.1016/j.conctc.2021.100745. eCollection 2021 Jun.
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.
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.
We expect that PIO will be an adequate adjuvant to the standard cryptococcosis' treatment.
ICTRP/WHO (and International Clinical Trial Registry Plataform (ICTRP/WHO) (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR-9fv3f4), RBR-9fv3f4 (http://www.ensaiosclinicos.gov.br/rg/RBR-9fv3f4). UTN Number: U1111-1226-1535. Ethical approvement number: CAAE 17377019.0.0000.5149.
隐球菌病每年影响超过22万名患者，即便使用标准治疗方案（两性霉素B（AMB）、5-氟胞嘧啶（5-FC）和氟康唑），死亡率仍很高。AMB毒性大，且巴西目前没有5-FC。在一项临床前研究中，吡格列酮（PIO——一种抗糖尿病药物）降低了AMB的毒性，提高了小鼠存活率，降低了发病率，并减轻了脑和肺中的真菌负荷。本试验的目的是评估PIO联合标准抗真菌治疗对人类隐球菌病的疗效和安全性。
将对来自巴西贝洛奥里藏特的患者进行一项1/2期、随机、双盲、安慰剂对照试验。他们将被分为三组（安慰剂组、每日15毫克PIO组或每日45毫克PIO组），并在隐球菌病治疗的诱导期额外服用一片药。我们的假设是接受治疗的患者存活率会提高，因此主要结局将是死亡率。将对患者的存活情况、副作用、真菌负荷以及血液和脑脊液中的炎症介质进行监测。随访将持续60天。
我们预计PIO将成为标准隐球菌病治疗的合适辅助药物。
ICTRP/世界卫生组织（以及国际临床试验注册平台（ICTRP/世界卫生组织）（http://apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR-9fv3f4），RBR-9fv3f4（http://www.ensaiosclinicos.gov.br/rg/RBR-9fv3f4）。UTN编号：U1111-1226-1535。伦理批准编号：CAAE 17377019.0.0000.5149。
