干扰素 β-1b 联合瑞德西韦治疗高风险住院 2019 年冠状病毒病（COVID-19）患者的早期治疗：一项 2 期开放标签随机对照试验。
Early Treatment of High-Risk Hospitalized Coronavirus Disease 2019 (COVID-19) Patients With a Combination of Interferon Beta-1b and Remdesivir: A Phase 2 Open-label Randomized Controlled Trial.
机构信息
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China.
出版信息
Clin Infect Dis. 2023 Feb 8;76(3):e216-e226. doi: 10.1093/cid/ciac523.
BACKGROUND
Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients.
METHODS
We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0).
RESULTS
Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4.
CONCLUSIONS
Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.
CLINICAL TRIALS REGISTRATION
NCT04647695.
背景
早期抗病毒治疗对治疗 2019 年冠状病毒病（COVID-19）有效。我们评估了干扰素 beta-1b 和瑞德西韦联合治疗住院 COVID-19 患者的疗效和安全性。
方法
我们进行了一项多中心、前瞻性、开放标签、随机对照试验，纳入了因 COVID-19 住院的高危成年人。患者被随机分配至干扰素 beta-1b 每日 1600 万单位 5 天疗程加瑞德西韦 200mg 负荷剂量（第 1 天）随后每日 100mg 疗程（第 2-5 天）（联合组），或接受类似方案的瑞德西韦单药治疗（对照组）（1:1）。主要终点为症状完全缓解的时间（NEWS2=0）。
结果
共纳入 212 例患者。从症状发作开始治疗的中位时间为 3 天。中位年龄为 65 岁，159 例（75%）患者有慢性病。基线人口统计学特征相似。无死亡病例。对于主要终点，与对照组相比，联合组 NEWS2=0 的时间显著更快（4 天 vs 6.5 天；风险比[HR]，6.59；95%置信区间[CI]，6.1-7.09；P<0.0001）。对于次要终点，联合组鼻咽拭子（NPS）病毒载量（VL）转为阴性的时间更快（6 天 vs 8 天；HR，8.16；95%CI，7.79-8.52；P<0.0001），且更早出现血清 IgG 阳性（8 天 vs 10 天；HR，10.78；95%CI，9.98-11.58；P<0.0001）。所有不良事件随访时均已解决。联合组（HR，4.1；95%CI，1.9-8.6；P<0.0001）是与第 4 天 NEWS2=0 最显著相关的独立因素。
结论
干扰素 beta-1b 和瑞德西韦早期治疗在缓解症状、缩短病毒脱落和住院时间以及提高高危 COVID-19 患者的血清 IgG 阳性率方面优于瑞德西韦单药治疗，且安全。
临床试验注册
NCT04647695。
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