Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Jiao Liu; Xiaojun Pan; Sheng Zhang; Ming Li; Ke Ma; Cunyi Fan; Ying Lv; Xiangdong Guan; Yi Yang; Xiaofei Ye; Xingqi Deng; Yunfeng Wang; LunXiu Qin; Zhijie Xia; Zi Ge; Quanhong Zhou; Xian Zhang; Yun Ling; Tangkai Qi; Zhenliang Wen; Sisi Huang; Lidi Zhang; Tao Wang; Yongan Liu; Yanxia Huang; Wenzhe Li; Hangxiang Du; Yizhu Chen; Yan Xu; Qiang Zhao; Ren Zhao; Djillali Annane; Jieming Qu; Dechang Chen

doi:10.1016/j.lanwpc.2023.100694

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Lancet Reg Health West Pac. 2023 Apr:33:100694. doi: 10.1016/j.lanwpc.2023.100694. Epub 2023 Feb 6.

Authors

Jiao Liu¹, Xiaojun Pan¹, Sheng Zhang¹, Ming Li², Ke Ma³, Cunyi Fan⁴, Ying Lv⁵, Xiangdong Guan⁶, Yi Yang⁷, Xiaofei Ye⁸, Xingqi Deng⁹, Yunfeng Wang⁹, LunXiu Qin¹⁰, Zhijie Xia³, Zi Ge³, Quanhong Zhou¹¹, Xian Zhang¹¹, Yun Ling¹², Tangkai Qi¹³, Zhenliang Wen¹, Sisi Huang¹, Lidi Zhang¹, Tao Wang¹, Yongan Liu¹, Yanxia Huang¹, Wenzhe Li¹, Hangxiang Du¹, Yizhu Chen¹, Yan Xu¹, Qiang Zhao¹⁴, Ren Zhao¹⁵, Djillali Annane¹⁶, Jieming Qu¹⁷, Dechang Chen¹

Affiliations

¹ Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin 2nd Road, Shanghai, 200025, China.
² Office of the President, Zhoupu Hospital Affiliated to Shanghai Health Medical College, 1500 Zhouyuan Road, Shanghai, 201318, China.
³ Department of Emergency and Critical Care Medicine, Baoshan Campus of Huashan Hospital Affiliated Fudan University, 108 Luxiang Road, Baoshan District, Shanghai, 201907, China.
⁴ Orthopedic Department in Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
⁵ Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Jinshan District, Shanghai, 201508, China.
⁶ Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, China.
⁷ Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Hunan Road, Nanjing, 210009, China.
⁸ Department of Health Statistics, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
⁹ Department of Critical Care Medicine, Zhoupu Hospital, Pudong New Area, Shanghai＆Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, 1500 Zhouyuan Road, Pudong New Area, Shanghai, 201318, China.
¹⁰ Department of Surgery, Huashan Hospital, Fudan University, 12 Urumqi Road (M), Shanghai, 200040, China.
¹¹ Department of Critical Care Medicine, Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
¹² Department of Infection, Shanghai Public Health Clinical Center, 2901 Caolang Rd, Jinshan District, Shanghai, 201508, China.
¹³ Department of Infection and Immunity, Shanghai Public Health Clinical Center, 2901 Caolang Rd, Jinshan District, Shanghai, 201508, China.
¹⁴ Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
¹⁵ Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
¹⁶ General Intensive Care Unit, Raymond Poincaré Hospital (APHP), Laboratory of Inflammation and Infection U1173, University of Versailles SQY/INSERM 104 bd Raymond Poincaré, 92380, Garches, France.
¹⁷ Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Huangpu District, Shanghai, 200025, China.

Abstract

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities.

Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated.

Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76).

Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities.

Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

Keywords: Comorbidities; Efficacy; Paxlovid; SARS-CoV-2; Safety; Severe.