Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.
Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.
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DOI：
10.1016/j.eclinm.2021.100849
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发表时间：
2021-05
影响因子：
15.1
通讯作者：
Søgaard OS
中科院分区：
文献类型：
--
作者：
Gunst JD;Staerke NB;Pahus MH;Kristensen LH;Bodilsen J;Lohse N;Dalgaard LS;Brønnum D;Fröbert O;Hønge B;Johansen IS;Monrad I;Erikstrup C;Rosendal R;Vilstrup E;Mariager T;Bove DG;Offersen R;Shakar S;Cajander S;Jørgensen NP;Sritharan SS;Breining P;Jespersen S;Mortensen KL;Jensen ML;Kolte L;Frattari GS;Larsen CS;Storgaard M;Nielsen LP;Tolstrup M;Sædder EA;Østergaard LJ;Ngo HTT;Jensen MH;Højen JF;Kjolby M;Søgaard OS
跨膜蛋白丝氨酸2(TMPRSS2)是严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)进入细胞和感染所必需的。TMPRSS2抑制剂对冠状病毒病患者2019(新冠肺炎)的有效性和安全性尚未进行随机试验评估。我们在2020年4月4日至12月31日期间对确诊为SARS-CoV-2感染的住院患者进行了一项由调查者发起的双盲、随机、安慰剂对照的多中心试验。在入院48小时内，参与者被按2：1的比例随机分配给TMPRSS2抑制剂卡莫司坦甲磺酸盐200 mg，每天三次，连续5天或安慰剂。主要结果是出院时间或临床改善，以7分顺序评分中≥2分的改善来衡量。其他结果包括30天的死亡率、安全性和口咽病毒载量的变化。137名患者被分配接受卡莫司坦治疗，68名患者接受安慰剂治疗。临床改善的中位时间：卡莫司坦组为5天(四分位数范围为3~7)，安慰剂组为5天(IQR为2~10)(P=0.31)。与安慰剂组相比，卡莫司坦组30天死亡的风险比为0.82(95%可信区间[CI]，0.24至2.79；P=0.75)。两组不良事件发生的频率相似。从基线到第5天，卡莫司坦组病毒载量变化的中位数为-0.22log10拷贝/毫升(P<0.05)，安慰剂组为-0.82对数10拷贝/毫升(P<0.05)。根据这一方案，甲磺酸卡莫司坦治疗与新冠肺炎住院期间不良事件的增加无关，也不影响临床改善时间、进入ICU的进展或死亡率。ClinicalTrials.gov标识：NCT04321096。欧共体编号：2020年-001200-42。
The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials. We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05). Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.
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影响因子：
--
作者：
Hofmann-Winkler H;Moerer O;Alt-Epping S;Bräuer A;Büttner B;Müller M;Fricke T;Grundmann J;Harnisch LO;Heise D;Kernchen A;Pressler M;Stephani C;Tampe B;Kaul A;Gärtner S;Kramer S;Pöhlmann S;Winkler MS
通讯作者：
Winkler MS
影响因子：
11.8
作者：
Qin, Chuan;Zhou, Luoqi;Tian, Dai-Shi
通讯作者：
Tian, Dai-Shi
DOI：
10.1056/nejmoa2028836
发表时间：
2020-12-10
期刊：
The New England journal of medicine
影响因子：
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作者：
Stone JH;Frigault MJ;Serling-Boyd NJ;Fernandes AD;Harvey L;Foulkes AS;Horick NK;Healy BC;Shah R;Bensaci AM;Woolley AE;Nikiforow S;Lin N;Sagar M;Schrager H;Huckins DS;Axelrod M;Pincus MD;Fleisher J;Sacks CA;Dougan M;North CM;Halvorsen YD;Thurber TK;Dagher Z;Scherer A;Wallwork RS;Kim AY;Schoenfeld S;Sen P;Neilan TG;Perugino CA;Unizony SH;Collier DS;Matza MA;Yinh JM;Bowman KA;Meyerowitz E;Zafar A;Drobni ZD;Bolster MB;Kohler M;D'Silva KM;Dau J;Lockwood MM;Cubbison C;Weber BN;Mansour MK;BACC Bay Tocilizumab Trial Investigators
通讯作者：
BACC Bay Tocilizumab Trial Investigators
影响因子：
7.6
作者：
Zhou Y;Vedantham P;Lu K;Agudelo J;Carrion R Jr;Nunneley JW;Barnard D;Pöhlmann S;McKerrow JH;Renslo AR;Simmons G
通讯作者：
Simmons G
DOI：
10.1056/nejmoa2033700
发表时间：
2021-02-18
期刊：
The New England journal of medicine
影响因子：
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作者：
Libster R;Pérez Marc G;Wappner D;Coviello S;Bianchi A;Braem V;Esteban I;Caballero MT;Wood C;Berrueta M;Rondan A;Lescano G;Cruz P;Ritou Y;Fernández Viña V;Álvarez Paggi D;Esperante S;Ferreti A;Ofman G;Ciganda Á;Rodriguez R;Lantos J;Valentini R;Itcovici N;Hintze A;Oyarvide ML;Etchegaray C;Neira A;Name I;Alfonso J;López Castelo R;Caruso G;Rapelius S;Alvez F;Etchenique F;Dimase F;Alvarez D;Aranda SS;Sánchez Yanotti C;De Luca J;Jares Baglivo S;Laudanno S;Nowogrodzki F;Larrea R;Silveyra M;Leberzstein G;Debonis A;Molinos J;González M;Perez E;Kreplak N;Pastor Argüello S;Gibbons L;Althabe F;Bergel E;Polack FP;Fundación INFANT–COVID-19 Group
通讯作者：
Fundación INFANT–COVID-19 Group