UNASSIGNED: We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers.
UNASSIGNED: We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events.
UNASSIGNED: Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators.
UNASSIGNED: NCT04006873 (02/07/2019).
■我们进行了随机,双盲,安慰剂对照,诺丁汉大学医院两期交叉试验(2019-2020年)。使用MRI测量TEZ/IVA对肠道生理的影响。参与者被随机分配到治疗序列AB或BA(A:TEZ/IVA,B:安慰剂,每28天),有28天的冲洗期。参与者在基线和每次治疗19-23天后进行了系列MRI扫描。由于COVID-19大流行,一项方案修订允许在TEZ/IVA之前和期间进行观察者-盲比较.在这种情况下,参与者并非对治疗视而不见,但研究人员仍然视而不见.主要结果是口盲肠转运时间(OCTT)。次要结果包括MRI指标,症状和粪便生物标志物。
■我们随机分配了13名参与者。在COVID-19大流行之前,有8名参与者完成了完整的方案,其中1名退出。其余4名参与者遵循修订后的协议。对于OCTT,安慰剂和TEZ/IVA之间没有显着差异(TEZ/IVA>360分钟[225,>360]与安慰剂330分钟[285,>360],p=0.8)或次要结果。无不良事件发生。
■我们的数据有助于CFTR调节剂肺外效应的研究空白。我们发现TEZ/IVA后对肠道功能的MRI指标没有影响,胃肠道症状或大便钙卫蛋白。通过更大的研究可能可以检测到影响,更长的治疗或更有效的CFTR调节剂。
■NCT04006873(02/07/2019)。