Lehr Thorsten, Meiser Peter, Selzer Dominik, Rixecker Torben, Holzer Frank, Mösges Ralph, Smola Sigrun, Bals Robert
Saarland University, Saarbruecken, Germany.
Ursapharm Arzneimittel GmbH, Saarbruecken, Germany.
JAMA Intern Med. 2025 Sep 2. doi: 10.1001/jamainternmed.2025.4283.
Limited pharmaceutical options exist for preexposure prophylaxis of COVID-19 beyond vaccination. Azelastine, an antihistamine nasal spray used for decades to treat allergic rhinitis, has in vitro antiviral activity against respiratory viruses, including SARS-CoV-2.
To determine the efficacy and safety of azelastine nasal spray for prevention of SARS-CoV-2 infections in healthy adults.
DESIGN, SETTING, AND PARTICIPANTS: A phase 2, double-blind, placebo-controlled, single-center trial was conducted from March 2023 to July 2024. Healthy adults from the general population were enrolled at the Saarland University Hospital in Germany.
Participants were randomly assigned 1:1 to receive azelastine, 0.1%, nasal spray or placebo 3 times daily for 56 days. SARS-CoV-2 rapid antigen testing (RAT) was conducted twice weekly, with positive results confirmed by polymerase chain reaction (PCR). Symptomatic participants with negative RAT results underwent multiplex PCR testing for respiratory viruses.
The primary end point was the number of PCR-confirmed SARS-CoV-2 infections during the study.
A total of 450 participants were randomized, with 227 assigned to azelastine and 223 to placebo; 299 (66.4%) were female, 151 (33.6%) male, with a mean (SD) age of 33.0 (13.3) years. Most were White (417 [92.7%]), with 4 (0.9%) African, 22 (4.9%) Asian, and 7 (1.6%) of other ethnicity. In the intention-to-treat (ITT) population, the incidence of PCR-confirmed SARS-CoV-2 infection was significantly lower in the azelastine group (n = 5 [2.2%]) compared with the placebo group (n = 15 [6.7%]) (OR, 0.31; 95% CI, 0.11-0.87). As secondary end points, azelastine demonstrated an increase in mean (SD) time to SARS-CoV-2 infection among infected participants (31.2 [9.3] vs 19.5 [14.8] days), a reduction of the overall number of PCR-confirmed symptomatic infections (21 of 227 participants vs 49 of 223 participants), and a lower incidence of PCR-confirmed rhinovirus infections (1.8% vs 6.3%). Adverse events were comparable between the groups.
In this single-center trial, azelastine nasal spray was associated with reduced risk of SARS-CoV-2 respiratory infections. These findings support the potential of azelastine as a safe prophylactic approach warranting confirmation in larger, multicentric trials.
EudraCT number: 2022-003756-13.
除疫苗接种外，用于新冠病毒暴露前预防的药物选择有限。氮卓斯汀是一种用于治疗过敏性鼻炎数十年的抗组胺鼻喷雾剂，对包括严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在内的呼吸道病毒具有体外抗病毒活性。
确定氮卓斯汀鼻喷雾剂预防健康成年人感染SARS-CoV-2的疗效和安全性。
设计、地点和参与者：2023年3月至2024年7月进行了一项2期双盲、安慰剂对照、单中心试验。德国萨尔州大学医院招募了来自普通人群的健康成年人。
参与者按1:1随机分配，每天3次接受0.1%氮卓斯汀鼻喷雾剂或安慰剂，共56天。每周进行两次SARS-CoV-2快速抗原检测（RAT），阳性结果通过聚合酶链反应（PCR）确认。RAT结果为阴性的有症状参与者接受呼吸道病毒多重PCR检测。
主要终点是研究期间PCR确诊的SARS-CoV-2感染病例数。
共450名参与者被随机分组，227名分配到氮卓斯汀组，223名分配到安慰剂组；299名（6六十六点4%）为女性，151名（33.6%）为男性，平均（标准差）年龄为33.0（13.3）岁。大多数为白人（417名[92.7%]），4名（0.9%）为非洲人，22名（4.9%）为亚洲人，7名（1.6%）为其他种族。在意向性分析（ITT）人群中氮卓斯汀组PCR确诊的SARS-CoV-2感染发生率（n = 5 [2.2%]）显著低于安慰剂组（n = 15 [6.7%]）（比值比，0.31；95%置信区间，0.11 - 0.87）。作为次要终点，氮卓斯汀使感染参与者中SARS-CoV-2感染的平均（标准差）时间增加（31.2 [9.3]天对19.5 [14.8]天），PCR确诊的有症状感染总数减少（227名参与者中的21名对223名参与者中的49名），PCR确诊的鼻病毒感染发生率降低（1.8%对6.3%）。两组不良事件相当。
在这项单中心试验中，氮卓斯汀鼻喷雾剂与SARS-CoV-2呼吸道感染风险降低相关。这些发现支持氮卓斯汀作为一种安全预防方法的潜力，需要在更大规模的多中心试验中得到证实。
欧洲临床试验数据库（EudraCT）编号：2022 - 003756 - 13 。
