Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection - A randomized clinical trial
Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection - A randomized clinical trial
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DOI：
10.1001/jama.281.19.1797
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发表时间：
1999-05-19
影响因子：
120.7
通讯作者：
Hayden, FG
中科院分区：
文献类型：
--
作者：
Turner, RB;Wecker, MT;Hayden, FG
大多数鼻病毒亚型与细胞的粘附依赖于细胞受体，即细胞间粘附分子1（ICAM-1）。一种重组可溶性细胞间粘附分子-1（tremacamra，以前的BIRR 4）在早期研究中显示出可能的疗效。目的确定鼻内施用tremacamra在人类实验性鼻病毒感冒中的疗效和安全性。设计1996年1月至3月进行的四项随机、双盲、安慰剂对照试验，背景和受试者年龄在18至60岁之间的志愿者，其对攻毒病毒的抗体滴度为1：4或更低。在研究第0 - 8天，受试者在酒店房间隔离;记录症状直至第14天。共198例受试者接受随机化，其中196例接受药物或安慰剂，并纳入安全性分析。干预Tremacamra或安慰剂在鼻病毒39型接种前7小时（接种前研究）或接种后12小时（接种后研究）开始给药。Tremacamra作为吸入溶液或粉末（在总共4个研究中，每种在接种前和接种后给予）和安慰剂，在第1天至第7天期间每天以3小时的间隔给予6剂。活性治疗的接受者接受367 μ g的tremacamra/ml/剂量，总共4.4mg/d。主要结果测量tremacamra对感染的作用，如通过病毒分离和血清转化所确定的，以及如通过症状评分、临床感冒和鼻粘液重量所确定的疾病。结果安慰剂组96例受试者中共有88例（92%）感染，活性治疗组81例受试者中共有69例（85%）感染（P= 0.19）。对于安慰剂与曲马卡姆拉，分别，总症状评分（+/- 95%置信区间[CI]）为17.6（+/- 2.7）vs 9.6（+/-2.9），临床感冒的比例为64/96（67% +/- 9%）vs 36/81（44% +/- 11%），鼻粘液重量为32.9（+/- 8.8）g vs 14.5（+/- 9.4）g（P
Context Attachment of most rhinovirus subtypes to cells depends on a cellular receptor, the intercellular adhesion molecule 1 (ICAM-1). A recombinant soluble ICAM-1 (tremacamra, formerly BIRR 4) has shown possible efficacy in early studies.Objective To determine the efficacy and safety of intranasal administration of tremacamra in experimental rhinovirus colds in humans.Design Four randomized, double-blind, placebo-controlled trials conducted in January to March 1996,Setting and Subjects Volunteers between the ages of 18 and 60 years who had an antibody titer of 1:4 or less to the challenge virus. Subjects were isolated in a hotel room during study days 0 to 8; symptoms were recorded through day 14, A total of 198 subjects were randomized, of whom 196 received drug or placebo and were included in the safety analysis. A total of 177 subjects were included in the efficacy analysis.Interventions Tremacamra or placebo was given beginning 7 hours before inoculation with rhinovirus type 39 (preinoculation studies) or 12 hours after (postinoculation studies). Tremacamra as an inhaled solution or as a powder (each given preinoculation and postinoculation for a total of 4 studies) and placebo were given in 6 doses at 3-hour intervals daily during days 1 through 7, Recipients of active treatment received 367 mu g of tremacamra per nostril per dose for a total of 4.4 mg/d.Main Outcome Measures Effect of tremacamra on infection, as determined by virus isolation and seroconversion, and on illness, as determined by symptom scores, clinical colds, and nasal mucus weights. Treatment-by-study interaction was not significant, so results were pooled for the main analysis.Results A total of 88 (92%) of the 96 subjects in the placebo groups and 69 (85%) of the 81 subjects in the active treatment groups were infected (P=.19). For placebo vs tremacamra, respectively, the total symptom score (+/- 95% confidence interval [CI]) was 17.6 (+/- 2.7) vs 9.6 (+/- 2.9), the proportion of clinical colds was 64/96 (67% +/- 9%) vs 36/81 (44% +/- 11%), and the nasal mucus weight was 32.9 (+/- 8.8) g vs 14.5 (+/- 9.4) g (P