CHILDHOOD ASTHMA PREVENTION STUDY (CAPS) FOR PACRN

PACRN 儿童哮喘预防研究 (CAPS)

基本信息

批准号：
6184633
负责人：
ROBERT S ZEIGER
金额：
$ 63.92万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-30 至 2004-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6184633
关键词：
antiantibody asthma child (0-11) clinical research clinical trials cooperative study disease /disorder prevention /control human subject human therapy evaluation immunoglobulin G longitudinal human study monoclonal antibody placebos respiratory disorder chemotherapy

项目摘要

Asthma is the most common chronic respiratory disease of childhood with prevalence, morbidity and mortality increasing in epidemic proportions throughout the world despite better diagnosis and improved anti-inflammatory treatment. Recombinant humanized monoclonal anti-IgE is the most promising immunomodulatory agent available today to non-specifically modulate IgE, the major effector molecule in allergic asthma. Anti-IgE reduces free IgE and IgE receptors more than 95 percent, improves asthma symptoms, lung function, and reduces prn bronchodilator use and corticosteroid use in moderate to severe persistent allergic asthma in adolescents and adults. Proposed here are two projects, each prospective, randomized, masked, and placebo-controlled, to evaluate the effectiveness and safety of anti-IgE in primary and secondary asthma prevention in children. Proposal number 1 or primary asthma prevention will determine whether anti-IgE can prevent the development of asthma in 232 high-risk infants 1 to 2 years of age with atopic dermatitis, food allergy, or allergic rhinitis and specific IgE and a parental history of atopy. Patients will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo, and followed for the development of asthma for 3 years. Secondary objectives include determination if anti-IgE compared to placebo differ with respect to (1) the onset of at least mild persistent asthma, (2) lung impedance and bronchial responsiveness determined by impulse oscillation, (3) skin test reactivity and markers of inflammation, (4) effect on atopic disorders, and (5) long-term safety and growth. Proposal number 2 or secondary asthma prevention will determine the effectiveness of anti-IgE compared to placebo to reduce inhaled corticosteroid (ICS) requirements (steroid sparing) in 140 children 5-12 years of age with moderate to severe persistent allergic asthma requiring ICS. Subjects will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo for 1 year, and followed in two phases. During Phase I or the 12-week adjunctive phase, patients will maintain their stable dose of ICS, and during Phase II or the 40-week ICS withdrawal phase, subjects will have their ICS reduced according to protocol. The efficacy and safety of anti- IgE therapy versus placebo will be compared in terms of (1) the reduction in ICS dose measured by real time monitoring of ICS use electronically (primary aim), (2) asthma symptom scores, medication use, and peak expiratory flow levels monitored electronically, (3) levels of lung function and bronchial responsiveness, (4) humanistic and pharmacoeconomic measures, (6) skin test reactivity and markers of inflammation, (7) somatic growth, and (8) adverse events.

哮喘是儿童期最常见的慢性呼吸道疾病，尽管有了更好的诊断和改进的抗炎治疗，但其患病率、发病率和死亡率在世界范围内呈流行趋势。重组人源化单克隆抗 IgE 是当今最有前途的免疫调节剂，可非特异性调节 IgE（过敏性哮喘的主要效应分子）。抗 IgE 可以减少 95% 以上的游离 IgE 和 IgE 受体，改善哮喘症状、肺功能，并减少青少年和成人中度至重度持续性过敏性哮喘中 prn 支气管扩张剂和皮质类固醇的使用。这里提出了两个项目，每个项目都是前瞻性的、随机的、隐蔽的和安慰剂对照的，以评估抗 IgE 在儿童一级和二级哮喘预防中的有效性和安全性。第 1 号提案或初级哮喘预防将确定抗 IgE 是否可以预防 232 名 1 至 2 岁高危婴儿患哮喘，这些婴儿患有特应性皮炎、食物过敏或过敏性鼻炎以及特异性 IgE 和父母特应性病史。患者将被随机分为抗 IgE 组或安慰剂组，每两个月皮下注射抗 IgE 组或安慰剂组，并随访 3 年哮喘的发生情况。次要目标包括确定抗 IgE 与安慰剂相比在以下方面是否存在差异：(1) 至少轻度持续性哮喘的发作，(2) 通过脉冲振荡确定的肺阻抗和支气管反应性，(3) 皮试反应性和炎症标志物，（4）对特应性疾病的影响，以及（5）长期安全性和生长。第 2 号提案或二级哮喘预防将确定抗 IgE 与安慰剂相比的有效性，以减少 140 名 5-12 岁患有需要 ICS 的中度至重度持续性过敏性哮喘儿童的吸入皮质类固醇 (ICS) 需求（类固醇节约）。受试者将被随机分为抗 IgE 组或安慰剂组，每两个月皮下注射一次抗 IgE 或安慰剂，持续 1 年，然后分两个阶段进行随访。在第一阶段或12周的辅助阶段，患者将维持稳定的ICS剂量，在第二阶段或40周的ICS停药阶段，受试者将根据方案减少ICS的剂量。抗 IgE 治疗与安慰剂的疗效和安全性将在以下方面进行比较：(1) 通过实时电子监测 ICS 使用情况测量的 ICS 剂量减少（主要目标），(2) 哮喘症状评分、药物使用和电子监测呼气峰流量水平，(3) 肺功能和支气管反应水平，(4) 人文和药物经济措施，(6) 皮试反应性和炎症标志物，(7) 体细胞生长，以及 (8) 不良事件。