Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial

Media type: E-Article
Title: Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial
Contributor: Florescu, Simin; Stanciu, Delia; Zaharia, Mihaela; Kosa, Alma; Codreanu, Daniel; Kidwai, Aneela; Masood, Sobia; Kaye, Callum; Coutts, Amanda; MacKay, Lynn; Summers, Charlotte; Polgarova, Petra; Farahi, Neda; Fox, Eleonore; McWilliam, Stephen; Hawcutt, Daniel; Rad, Laura; O’Malley, Laura; Whitbread, Jennifer; Jones, Dawn; Dore, Rachael; Saunderson, Paula; Kelsall, Olivia; Cowley, Nicholas; [...]
Published: American Medical Association (AMA), 2023
Published in: JAMA
Extent: 39
Language: English
DOI: 10.1001/jama.2022.23257
ISSN: 0098-7484
Keywords: General Medicine
Abstract: <jats:sec id="ab-joi220139-4"><jats:title>Importance</jats:title><jats:p>The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.</jats:p></jats:sec><jats:sec id="ab-joi220139-5"><jats:title>Objective</jats:title><jats:p>To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.</jats:p></jats:sec><jats:sec id="ab-joi220139-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.</jats:p></jats:sec><jats:sec id="ab-joi220139-7"><jats:title>Interventions</jats:title><jats:p>Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).</jats:p></jats:sec><jats:sec id="ab-joi220139-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.</jats:p></jats:sec><jats:sec id="ab-joi220139-9"><jats:title>Results</jats:title><jats:p>Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR &amp;gt;0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.</jats:p></jats:sec><jats:sec id="ab-joi220139-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.</jats:p></jats:sec>
Description: <jats:sec id="ab-joi220139-4"><jats:title>Importance</jats:title><jats:p>The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.</jats:p></jats:sec><jats:sec id="ab-joi220139-5"><jats:title>Objective</jats:title><jats:p>To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.</jats:p></jats:sec><jats:sec id="ab-joi220139-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.</jats:p></jats:sec><jats:sec id="ab-joi220139-7"><jats:title>Interventions</jats:title><jats:p>Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).</jats:p></jats:sec><jats:sec id="ab-joi220139-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.</jats:p></jats:sec><jats:sec id="ab-joi220139-9"><jats:title>Results</jats:title><jats:p>Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR &amp;gt;0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.</jats:p></jats:sec><jats:sec id="ab-joi220139-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.</jats:p></jats:sec>
Footnote:

Search in field:

Recently searched for: