Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
Division of Allergy and Clinical Immunology, Department of Medicine, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
JAMA Intern Med. 2023 Sep 1;183(9):944-952. doi: 10.1001/jamainternmed.2023.2986.
Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling.
To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy.
DESIGN, SETTING, AND PARTICIPANTS: This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies.
Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm).
The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp).
A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred.
In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label.
ClinicalTrials.gov Identifier: NCT04454229.
被标记为青霉素过敏的患者中，真正过敏的不到 5%。在成年人中去除青霉素过敏标签的标准护理是专门的测试，包括皮试和皮内皮肤测试，然后用青霉素进行口服挑战。皮肤测试资源密集，限制了仅受过专业培训的医生进行实践，并限制了全球可能接受青霉素过敏去标签的人群。
确定直接口服青霉素挑战是否不劣于低风险青霉素过敏患者的青霉素皮肤测试标准护理加口服挑战。
设计、设置和参与者：这是一项平行的、2 臂的、非劣效性、开放标签、多中心、国际随机临床试验，在 6 个专门中心进行，3 个在美国和加拿大，3 个在澳大利亚，时间为 2021 年 6 月 18 日至 2022 年 12 月 2 日。符合条件的成年人 PEN-FAST 评分低于 3。PEN-FAST 是一种前瞻性衍生的和国际验证的临床决策规则，可在报告青霉素过敏的成年人中进行即时护理风险评估。
患者被随机分配到青霉素直接口服挑战（干预组）或青霉素皮肤测试标准护理加口服挑战（对照组）。
主要结局是在 1 小时内医生验证的免疫介导的口服青霉素挑战阳性，在意向治疗人群中。如果风险差异（RD）的单侧 95%置信区间（CI）不超过 5 个百分点（pp），则认为非劣效性成立。
共有 382 名成年人被随机分配，377 名患者（中位数[IQR]年龄，51[35-65]岁；247[65.5%]为女性）被纳入分析：干预组 187 名，对照组 190 名。大多数患者的 PEN-FAST 评分为 0 或 1。在干预组中有 1 名患者（0.5%）和对照组中有 1 名患者（0.5%）发生了主要结局，RD 为 0.0084 pp（90%CI，-1.22 至 1.24 pp）。单侧 95%CI 低于 5 个百分点的非劣效性边界。在口服青霉素挑战后的 5 天内，干预组记录了 9 例免疫介导的不良事件，对照组记录了 10 例（RD，-0.45 pp；95%CI，-4.87 至 3.96 pp）。没有发生严重不良事件。
在这项随机临床试验中，低风险青霉素过敏患者的直接口服青霉素挑战不劣于标准护理皮肤测试加口服挑战。在低风险病史的患者中，直接口服青霉素挑战是一种安全的程序，可以方便地去除青霉素过敏标签。
ClinicalTrials.gov 标识符：NCT04454229。
