McGill University, Montreal, Canada.
Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil.
Trials. 2022 Aug 2;23(1):624. doi: 10.1186/s13063-022-06587-0.
The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5.
This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0-50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the "Comité Local d'Éthique Pour la Recherche Biomédicale (CLERB) de l'Université de Parakou," Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries.
This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence.
ClinicalTrials.gov NCT04528823.
世界卫生组织建议对所有艾滋病毒感染者（PLHIV）和结核病患者的家庭接触者（HHC）进行结核病预防性治疗（TPT）。首选检测结核病感染（TBI）或排除结核病疾病（TBD），但如果无法进行这些检测，且无法获得这些检测（如五岁以下的 PLHIV 和 HHC），则不应成为障碍。对于不同风险人群（特别是五岁以上的 HHC）是否需要进行这些检测存在争议。
本研究是一项三臂、优势、集群随机对照临床试验，比较了在贝宁和巴西对 0-50 岁 HHC 的三种调查策略：（i）TST 或干扰素释放试验（IGRA）用于 TBI，如果 TST 或 IGRA 阳性，则进行 X 线胸片（CXR）以排除 TBD；（ii）与（i）相同，但用 GeneXpert（GX）代替 CXR；（iii）不进行 TBI 检测。所有策略均从症状筛查开始。集群定义为新诊断为肺结核 TBD 的同一索引患者的 HHC 成员。主要结局是在开始治疗肺结核 TBD 后 3 个月内开始 TPT 的 HHC 比例。次要结局包括社会成本、严重不良事件发生率和 TBD 患病率。将按年龄（<5 岁和≥5 岁）和索引患者微生物学状况进行分层分析。所有参与者均签署了知情同意书。该研究得到了麦吉尔大学健康中心研究所研究伦理委员会、巴西国家伦理委员会 CONEP 以及贝宁帕拉库大学“生物医学研究地方伦理委员会（CLERB）”的批准。研究结果将发表在主要医学期刊上，并在会议上、向世界卫生组织以及参与国家的国家和市级结核病规划报告，以提供决策依据。
这项随机试验旨在提供高质量的证据，为世卫组织关于家庭接触者调查的建议提供依据，因为目前这些建议是基于非常低质量的证据。
ClinicalTrials.gov NCT04528823。
