Varo Rosauro, Crowley Valerie M, Sitoe Antonio, Madrid Lola, Serghides Lena, Bila Rubao, Mucavele Helio, Mayor Alfredo, Bassat Quique, Kain Kevin C
ISGlobal, Barcelona Institute for Global Health, Hospital Clínic, Universitat de Barcelona, Rosselló 132, 5th Floor, 08036, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça, Rua 12, Vila da Manhiça, 1929, Maputo, Mozambique.
Malar J. 2017 May 23;16(1):215. doi: 10.1186/s12936-017-1858-0.
Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention.
In this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations.
Thirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters.
Adjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria. The trial is registered with Clinicaltrials.gov, NCT02694874.
尽管速效抗疟药已广泛应用且易于获得，但撒哈拉以南非洲地区严重疟疾的死亡率仍然很高。针对宿主对疟疾感染反应的辅助治疗可能会比单独使用抗疟药进一步降低死亡率。过氧化物酶体增殖物激活受体γ激动剂（如罗格列酮）已被证明可作用于与严重疟疾发病机制相关的多种途径，并可能作为辅助干预措施改善临床结局。
在本研究中，在莫桑比克评估了辅助使用罗格列酮治疗小儿非复杂性疟疾感染的安全性和耐受性，作为在小儿严重疟疾随机对照试验中进行评估的前奏。该研究是一项前瞻性、随机、双盲、安慰剂对照的IIa期试验，将罗格列酮（0.045毫克/千克/剂量）每日两次，共4天，与安慰剂作为辅助治疗，用于治疗患有非复杂性疟疾的儿童，同时给予莫桑比克标准治疗（青蒿素联合疗法科泰复）。主要结局是耐受性和安全性，包括临床、血液学、生化和心电图评估。
招募了30名儿童：20名被分配接受罗格列酮治疗，10名接受安慰剂治疗。罗格列酮治疗未诱发低血糖，也未显著改变临床、生化、血液学或心电图参数。
辅助使用罗格列酮治疗小儿非复杂性疟疾安全且耐受性良好，因此可以将其作为严重疟疾辅助治疗的评估范围扩大。该试验已在Clinicaltrials.gov注册，注册号为NCT02694874。
