Barcelona Institute for Global Health (ISGLOBAL), Barcelona, Spain.
Center for Biochemistry and Biophysics, Venezuelan Institute for Scientific Research (IVIC), Caracas, Distrito Capital, Venezuela, Bolivarian Republic of.
BMJ Open. 2021 Dec 31;11(12):e052897. doi: 10.1136/bmjopen-2021-052897.
Chagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and variable. Moreover, the high incidence of adverse events (AEs) with both drugs has hampered their widespread use. Trials in CCD adults showed that quantitative PCR (qPCR) assays remain negative for 12 months after standard-of-care (SoC) BZN treatment in ~80% patients. BZN pharmacokinetic data and the nonsynchronous nature of the proliferative mammal-dwelling parasite stage suggested that a lower BZN/NFX dosing frequency, combined with standard or extended treatment duration, might have the same or better efficacy than either drug SoC, with fewer AEs.
New ThErapies and Biomarkers for ChagaS infEctiOn (TESEO) is an open-label, randomised, prospective, phase-2 clinical trial, with six treatment arms (75 patients/arm, 450 patients). Primary objectives are to compare the safety and efficacy of two new proposed chemotherapy regimens of BZN and NFX in adults with CCD with the current SoC for BZN and NFX, evaluated by qPCR and biomarkers for 36 months posttreatment and correlated with CD conventional serology. Recruitment of patients was initiated on 18 December 2019 and on 20 May 2021, 450 patients (study goal) were randomised among the six treatment arms. The treatment phase was finalised on 18 August 2021. Secondary objectives include evaluation of population pharmacokinetics of both drugs in all treatment arms, the incidence of AEs, and parasite genotyping.
The TESEO study was approved by the National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), federal regulatory agency of the Plurinational State of Bolivia and the Ethics Committees of the participating institutions. The results will be disseminated via publications in peer-reviewed journals, conferences and reports to the NIH, FDA and participating institutions.
NCT03981523.
恰加斯病（CD）影响全球约 700 万人。苯硝唑（BZN）和硝呋莫司（NFX）是唯一批准用于 CD 化学治疗的药物。尽管这两种药物在急性和儿科感染中都非常有效，但它们在慢性 CD（CCD）成人中的疗效较低且各不相同。此外，两种药物的高不良反应（AE）发生率阻碍了它们的广泛应用。在 CCD 成人中进行的试验表明，在接受标准护理（SoC）BZN 治疗后，约 80%的患者在 12 个月内定量 PCR（qPCR）检测仍为阴性。BZN 药代动力学数据和增殖哺乳动物寄生虫阶段的非同步性质表明，较低剂量的 BZN/NFX 给药频率，结合标准或延长治疗时间，可能与 SoC 药物具有相同或更好的疗效，不良反应更少。
新疗法和恰加斯感染的生物标志物（TESEO）是一项开放性标签、随机、前瞻性、2 期临床试验，共有 6 个治疗组（每组 75 名患者，共 450 名患者）。主要目的是通过 qPCR 和生物标志物评估两种新的 BZN 和 NFX 化疗方案与当前 SoC 对 CCD 成人的安全性和疗效，治疗后 36 个月进行评估，并与 CD 常规血清学相关联。患者招募于 2019 年 12 月 18 日开始，2021 年 5 月 20 日，450 名患者（研究目标）在 6 个治疗组中随机分组。治疗阶段于 2021 年 8 月 18 日结束。次要目标包括评估所有治疗组中两种药物的群体药代动力学、不良反应发生率和寄生虫基因分型。
TESEO 研究得到了美国国立卫生研究院（NIH）、美国食品和药物管理局（FDA）、玻利维亚多民族国联邦监管机构和参与机构的伦理委员会的批准。研究结果将通过发表在同行评议期刊、会议和报告中传播给 NIH、FDA 和参与机构。
NCT03981523。
