{"id":21927,"date":"2022-07-17T04:48:00","date_gmt":"2022-07-16T20:48:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=21927"},"modified":"2022-07-17T10:44:57","modified_gmt":"2022-07-17T02:44:57","slug":"lancet-respir-med%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9a%e5%b7%b4%e7%91%9e%e5%85%8b%e6%9b%bf%e5%b0%bc%e4%b8%8e%e4%bd%8e%e5%a1%9e%e7%b1%b3%e6%9d%be%e6%b2%bb%e7%96%97%e6%96%b0%e5%86%a0%e8%82%ba","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=21927","title":{"rendered":"[Lancet Respir Med\u53d1\u8868\u8bba\u6587]\uff1a\u5df4\u745e\u514b\u66ff\u5c3c\u4e0e\u4f4e\u585e\u7c73\u677e\u6cbb\u7597\u65b0\u51a0\u80ba\u708e\u6210\u5e74\u4f4f\u9662\u60a3\u8005"},"content":{"rendered":"\n

ARTICLES|ONLINE FIRST<\/a><\/p>\n\n\n\n

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial<\/h1>\n\n\n\n

Cameron R Wolfe, Kay M Tomashek, Thomas F Patterson,\u00a0et al<\/h3>\n\n\n\n

Lancet Respir Med Published:May 23, 2022<\/h3>\n\n\n\n

DOI:https:\/\/doi.org\/10.1016\/S2213-2600(22)00088-1<\/a><\/h3>\n\n\n\n

Summary<\/h2>\n\n\n\n

Background<\/h3>\n\n\n\n

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.<\/p>\n\n\n\n

Methods<\/h3>\n\n\n\n

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 (\u226518 years) with COVID-19 who required supplemental oxygen administered by low-flow (\u226415 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 \u226518 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 (\u226410 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<\/a>, NCT04640168<\/a>.<\/p>\n\n\n\n

Findings<\/h3>\n\n\n\n

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\u00b73 years (SD 14\u00b70) 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\u00b70% [95% CI 83\u00b77 to 89\u00b76] in the baricitinib plus remdesivir plus placebo group and 87\u00b76% [84\u00b72 to 90\u00b73] in the dexamethasone plus remdesivir plus placebo group; risk difference 0\u00b76 [95% CI \u22123\u00b76 to 4\u00b78]; p=0\u00b791). 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\u00b701 (95% CI 0\u00b780 to 1\u00b727). 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\u00b75% [1\u00b76 to 13\u00b73]; p=0\u00b7014). 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\u00b70% [2\u00b78 to 9\u00b73]; p=0\u00b700041). 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\u00b77% [1\u00b78 to 13\u00b74]; p=0\u00b7012).<\/p>\n\n\n\n

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Interpretation<\/h3>\n\n\n\n

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.<\/p>\n\n\n\n

Funding<\/h3>\n\n\n\n

National Institute of Allergy and Infectious Diseases.<\/p>\n","protected":false},"excerpt":{"rendered":"

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