Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia.
Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia.
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DOI：
10.1136/bmjopen-2023-077946
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发表时间：
2023-09-28
期刊：
影响因子：
2.9
通讯作者：
Parry, Helen M.
中科院分区：
文献类型：
--
作者：
Barber, Vicki S.;Peckham, Nicholas;Duley, Lelia;Francis, Anne;Abhishek, Abhishek;Moss, Paul;Cook, Jonathan A.;Parry, Helen M.
免疫功能低下的人对疫苗接种的生物反应较差。本研究旨在确定慢性淋巴细胞白血病（CLL）患者在给予SARS-CoV-2疫苗增强剂前1周开始暂停布鲁顿酪氨酸激酶抑制剂治疗（BTKi） 3周，与继续使用BTKi相比，是否能改善疫苗免疫反应。一项开放标签、随机对照的优势试验将在大约10家英国国家卫生服务（NHS）医院的血液学诊所进行。样本量为120人，按1:1随机分为干预组和常规护理组。主要终点是在sars - cov -2加强疫苗接种后3周的抗刺突受体结合域（RBD）抗体水平。次要结果是增强疫苗接种后12周的RBD抗体水平、参与者疾病活动性的总体评估、血膜、全血细胞计数和乳酸脱氢酶水平、对生活质量的影响、自我报告的暂停或继续BTKi的依从性、针对刺突蛋白的T细胞应答和针对SARS-CoV-2病毒变体的相对中和抗体滴度。此外，还将调查同时接种流感疫苗与单独接种COVID-19疫苗的效果。初步分析将作为随机分组（“意向治疗”）进行。在抗尖峰rbd抗体水平的研究组之间的差异将使用混合效应回归模型进行估计，允许在参与者中聚集重复测量。该模型将根据随机化因素（一线或后续治疗）和从随机化前抗核衣壳抗体获得的既往感染状态作为固定效应进行调整。本研究已获得利兹东部研究伦理委员会和卫生研究管理局批准（REC参考：22/YH/0226， IRAS ID: 319057）。传播将通过同行评审出版物、通讯和会议进行。结果将传达给参与者、CLL患者和临床社区以及卫生政策制定者。ISRCTN14197181。
People who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi. An open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1:1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity, blood films, full blood count and lactate dehydrogenase levels, impact on quality of life, self-reported adherence with request to temporarily pause or continue BTKi, T cell response against spike protein and relative neutralising antibody titre against SARS-CoV-2 viral variants. Additionally, there will be an investigation of any effects in those given influenza vaccination contemporaneously versus COVID-19 alone. The primary analysis will be performed on the as randomised groups (‘intention to treat’). The difference between the study arms in anti-spike-RBD antibody level will be estimated using a mixed effects regression model, allowing for repeated measures clustered within participants. The model will be adjusted for randomisation factor (first line or subsequent line of therapy), and prior infection status obtained from prerandomisation antinucleocapsid antibodies as fixed effects. This study has been approved by Leeds East Research Ethics Committee and Health Research Authority (REC Reference:22/YH/0226, IRAS ID: 319057). Dissemination will be via peer-review publications, newsletters and conferences. Results will be communicated to participants, the CLL patient and clinical communities and health policy-makers. ISRCTN14197181.
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