Browsing by Author "Engemann, John J"
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Item Open Access Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.(The Lancet. Respiratory medicine, 2022-05-23) Wolfe, Cameron R; Tomashek, Kay M; Patterson, Thomas F; Gomez, Carlos A; Marconi, Vincent C; Jain, Mamta K; Yang, Otto O; Paules, Catharine I; Palacios, Guillermo M Ruiz; Grossberg, Robert; Harkins, Michelle S; Mularski, Richard A; Erdmann, Nathaniel; Sandkovsky, Uriel; Almasri, Eyad; Pineda, Justino Regalado; Dretler, Alexandra W; de Castilla, Diego Lopez; Branche, Angela R; Park, Pauline K; Mehta, Aneesh K; Short, William R; McLellan, Susan LF; Kline, Susan; Iovine, Nicole M; El Sahly, Hana M; Doernberg, Sarah B; Oh, Myoung-Don; Huprikar, Nikhil; Hohmann, Elizabeth; Kelley, Colleen F; Holodniy, Mark; Kim, Eu Suk; Sweeney, Daniel A; Finberg, Robert W; Grimes, Kevin A; Maves, Ryan C; Ko, Emily R; Engemann, John J; Taylor, Barbara S; Ponce, Philip O; Larson, LuAnn; Melendez, Dante Paolo; Seibert, Allan M; Rouphael, Nadine G; Strebe, Joslyn; Clark, Jesse L; Julian, Kathleen G; de Leon, Alfredo Ponce; Cardoso, Anabela; de Bono, Stephanie; Atmar, Robert L; Ganesan, Anuradha; Ferreira, Jennifer L; Green, Michelle; Makowski, Mat; Bonnett, Tyler; Beresnev, Tatiana; Ghazaryan, Varduhi; Dempsey, Walla; Nayak, Seema U; Dodd, Lori E; Beigel, John H; Kalil, Andre C; ACTT-4 Study GroupBackground
Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.Methods
In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.Findings
Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).Interpretation
In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.Funding
National Institute of Allergy and Infectious Diseases.Item Open Access Social Disadvantage, Politics, and Severe Acute Respiratory Syndrome Coronavirus 2 Trends: A County-level Analysis of United States Data.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-05) Mourad, Ahmad; Turner, Nicholas A; Baker, Arthur W; Okeke, Nwora Lance; Narayanasamy, Shanti; Rolfe, Robert; Engemann, John J; Cox, Gary M; Stout, Jason EBackground
Understanding the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for public health control efforts. Social, demographic, and political characteristics at the United States (US) county level might be associated with changes in SARS-CoV-2 case incidence.Methods
We conducted a retrospective analysis of the relationship between the change in reported SARS-CoV-2 case counts at the US county level during 1 June-30 June 2020 and social, demographic, and political characteristics of the county.Results
Of 3142 US counties, 1023 were included in the analysis: 678 (66.3%) had increasing and 345 (33.7%) nonincreasing SARS-CoV-2 case counts between 1 June and 30 June 2020. In bivariate analysis, counties with increasing case counts had a significantly higher Social Deprivation Index (median, 48 [interquartile range {IQR}, 24-72]) than counties with nonincreasing case counts (median, 40 [IQR, 19-66]; P = .009). Counties with increasing case counts were significantly more likely to be metropolitan areas of 250 000-1 million population (P < .001), to have a higher percentage of black residents (9% vs 6%; P = .013), and to have voted for the Republican presidential candidate in 2016 by a ≥10-point margin (P = .044). In the multivariable model, metropolitan areas of 250 000-1 million population, higher percentage of black residents, and a ≥10-point Republican victory were independently associated with increasing case counts.Conclusions
Increasing case counts of SARS-CoV-2 in the US during June 2020 were associated with a combination of sociodemographic and political factors. Addressing social disadvantage and differential belief systems that may correspond with political alignment will play a critical role in pandemic control.