Remdesivir for the Treatment of Covid-19 - Final Report
Beigel, John H; Tomashek, Kay M; Dodd, Lori E; Mehta, Aneesh K; Zingman, Barry S; Kalil, Andre C; Hohmann, Elizabeth; Chu, Helen Y; Luetkemeyer, Annie; Kline, Susan; Lopez de Castilla, Diego; Finberg, Robert W; Dierberg, Kerry; Tapson, Victor; Hsieh, Lanny; Patterson, Thomas F; Paredes, Roger; Sweeney, Daniel A; Short, William R; Touloumi, Giota; Lye, David Chien; Ohmagari, Norio; Oh, Myoung-Don; Ruiz-Palacios, Guillermo M; Benfield, Thomas; Fätkenheuer, Gerd; Kortepeter, Mark G; Atmar, Robert L; Creech, C Buddy; Lundgren, Jens; Babiker, Abdel G; Pett, Sarah; Neaton, James D; Burgess, Timothy H; Bonnett, Tyler; Green, Michelle; Makowski, Mat; Osinusi, Anu; Nayak, Seema; Lane, H Clifford; Ahn, Jenny; Ahuja, Neera; Alaaeddine, Ghina; Ali, Farhana; Amin, Alpesh N; Angus, Brian; Antoniadou, Anastasia; Arguinchona, Christa; Arguinchona, Henry; Atmar, Robert L; Babiker, Abdel G; Barmparessou, Zafeiria; Beigel, John H; Bell, Taison D; Benfield, Thomas; Benson, Constance A; Billings, Joanne; Boesecke, Christoph; Bonnett, Tyler; Branche, Angela R; Burgess, Timothy H; Cantos, Valeria D; Cao, Huyen; Chambers, Susan E; Chary, Aarthi; Chrysanthidis, Theofilos; Chu, Helen Y; Chung, Kevin K; Cohen, Stuart H; Colombo, Christopher J; Colombo, Rhonda E; Creech, C Buddy; Crouch, Pierre-Cedric B; Davey, Richard T; Dempsey, Walla; Dierberg, Kerry; Dodd, Lori E; Duncan, Christopher J A; Eckhardt, Benjamin; El Sahly, Hana M; Elsafy, Mohamed; Engel, Theresa; Erdmann, Nathaniel; Falsey, Ann R; Fatkenheuer, Gerd; Ferreira, Jennifer L; Finberg, Robert W; Follmann, Dean; Frank, Maria; Ganesan, Anuradha; George, Sarah L; Germain Seymour, Jack David; Gerstoft, Jan; Gettinger, Nikki; Gioukari, Vicky; Goepfert, Paul; Goodman, Anna; Green, Margaret; Green, Michelle; Grein, Jonathan; Grossberg, Robert; Helleberg, Marie; Hewlett, Angela; Hohmann, Elizabeth; Holodniy, Mark; Hsieh, Lanny; Huprikar, Nikhil; Hynes, Noreen A; Jackson, Patrick E H; Jang, Hannah; Javeri, Heta; Jensen, Tomas; Jilg, Nikolaus; Johansen, Isik; Jung, Jongtak; Jurao, Robert; Kalil, Andre C; Kalomenidis, Ioannis; Kim, Eu Suk; Kline, Susan; Knudsen, Lene; Koehler, Philipp; Koo, Hyung; Kortepeter, Mark G; Kotloff, Karen L; Koulouris, Nikolaos; Krueger, Karen; Lalani, Tahaniyat; Lane, H Clifford; Larson, LuAnn; Lee, Marina; Lee, Tida; Lindegaard, Birgitte; Lindholm, David A; Llewelyn, Martin; Lopez de Castilla, Diego; Luetkemeyer, Annie; Lundgren, Jens; Lye, David Chien; Madsen, Lone W; Makowski, Mat; Malin, Jakob J; Marks, G Lynn; Martinez-Orozco, Jose Arturo; Mateu, Lourdes; Maves, Ryan C; McGill, Fiona; McLellan, Susan L F; Mehta, Aneesh K; Mende, Katrin; Merrick, Blair; Metallidis, Simeon; Mikami, Ayako; Minton, Jane; Munoz, Jose; Nadeau, Kari; Nayak, Seema; Neaton, James D; Neumann, Henry J; Nielsen, Henrik; Nomicos, Effie; Noren, Brooke; Novak, Richard M; Oh, Myoung-Don; Ohmagari, Norio; Ong, Sean W X; Ortiz, Justin R; Osinusi, Anu; Ostergaard, Lars; Paredes, Roger; Park, Wan Beom; Patterson, Thomas F; Paules, Catharine I; Pett, Sarah; Philips, Barbara; Pikaart-Tautges, Rhonda; Ponce de Leon, Alfredo; Price, D Ashley; Proschan, Michael; Protopapas, Konstantinos; Rajme, Sandra; Regalado Pineda, Justino; Rice, Todd W; Riedo, Francis X; Riska, Paul F; Roldan, Montserrat; Rouphael, Nadine G; Ruiz-Palacios, Guillermo M; Sauer, Lauren M; Short, William R; Staerke, Nina; Stephan, Christoph; Stephens, David S; Sutterwala, Fayyaz; Sweeney, Daniel A; Swiatlo, Edwin; Taiwo, Babafemi; Tapson, Victor; Tebas, Pablo; Tennant, Janice; Thompson, George R 3rd; Thomsen, Isaac; Tomashek, Kay M; Torgersen, Jessie; Torres-Soto, Mariam; Touloumi, Giota; Traenkner, Jessica J; Utz, Gregory C; Uyeki, Timothy M; Van Winkle, Jason W; Voell, Jocelyn D; Vu, Trung; Wald, Anna; Walker, Robert; Walter, Emmanuel B; Wang, Jennifer P; Wang, Jing; Wasmuth, Jan-Christian; Weise, Lothar; Wendrow, Andrea; Wessolossky, Mireya; Whitaker, Jennifer; Widmer, Kyle; Wierzbicki, Michael R; Wolf, Timo; Wolfe, Cameron; Wolff, Peter; Yang, Otto O; Young, Heather; Zakynthinos, Spyros G; Zingman, Barry S
BACKGROUND:Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS:We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS:A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS:Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
PMID: 32445440
ISSN: 1533-4406
CID: 4637302
Characterization of Myocardial Injury in Patients With COVID-19
Giustino, Gennaro; Croft, Lori B; Stefanini, Giulio G; Bragato, Renato; Silbiger, Jeffrey J; Vicenzi, Marco; Danilov, Tatyana; Kukar, Nina; Shaban, Nada; Kini, Annapoorna; Camaj, Anton; Bienstock, Solomon W; Rashed, Eman R; Rahman, Karishma; Oates, Connor P; Buckley, Samantha; Elbaum, Lindsay S; Arkonac, Derya; Fiter, Ryan; Singh, Ranbir; Li, Emily; Razuk, Victor; Robinson, Sam E; Miller, Michael; Bier, Benjamin; Donghi, Valeria; Pisaniello, Marco; Mantovani, Riccardo; Pinto, Giuseppe; Rota, Irene; Baggio, Sara; Chiarito, Mauro; Fazzari, Fabio; Cusmano, Ignazio; Curzi, Mirko; Ro, Richard; Malick, Waqas; Kamran, Mazullah; Kohli-Seth, Roopa; Bassily-Marcus, Adel M; Neibart, Eric; Serrao, Gregory; Perk, Gila; Mancini, Donna; Reddy, Vivek Y; Pinney, Sean P; Dangas, George; Blasi, Francesco; Sharma, Samin K; Mehran, Roxana; Condorelli, Gianluigi; Stone, Gregg W; Fuster, Valentin; Lerakis, Stamatios; Goldman, Martin E
BACKGROUND:Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data. OBJECTIVES/OBJECTIVE:This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. METHODS:We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. RESULTS:A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities. CONCLUSIONS:Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.
PMID: 33121710
ISSN: 1558-3597
CID: 4646832