According to a study published in Journal of the American Medical Association Network, among critically ill patients with COVID-19 randomized to receive one or more therapeutic interventions, there was an elevated probability of improved 180-day mortality among patients treated with interleukin-6 receptor antagonists (IL-6 RAs) and antiplatelet agents.

In this study, researchers aimed to ascertain the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.

The researchers used a prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains. A total of 4,869 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 finished on March 2, 2022.

The participants were randomized to receive one or more interventions within six treatment domains: immune modulators (n = 2,274), convalescent plasma (n = 2,011), antiplatelet therapy (n = 1,557), anticoagulation (n = 1,033), antivirals (n = 726), and corticosteroids (n = 401).

The primary outcome was survival through Day 180, evaluated using a Bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented enhanced survival (superiority), while an HR greater than 1 represented deteriorated survival (harm); futility was represented by a relative improvement less than 20% in outcome, revealed by an HR greater than 0.83.

Among 4,869 randomized patients (average age, 59.3 years; 1,537 [32.1%] women), 4,107 (84.3%) had known vital status and 2,590 (63.1%) were alive at Day 180.

IL-6 RAs had a greater than 99.9% probability of improving 6-month survival, and antiplatelet agents had a 95% probability of improving 6-month survival compared with the control.

In contrast, survival was not enhanced with therapeutic anticoagulation, convalescent plasma, or lopinavir-ritonavir, and the probability that survival was exacerbated with hydroxychloroquine alone or in combination with lopinavir-ritonavir was 96.8%.

The results indicated that the probability of trial-defined statistical futility (HR >0.83) was elevated for therapeutic anticoagulation (99.9%), convalescent plasma (99.2%), and lopinavir-ritonavir (96.6%). The probabilities of harm from hydroxychloroquine (96.9%) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%) were elevated.

Corticosteroids did not improve long-term outcomes, and the corticosteroid domain was terminated 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.

In the study, health-related quality of life (HRQoL) was favorable for the majority of patients but an estimated one in three patients reported at least moderate disability that continued through 6 months (although participants’ baseline disability was not known). Probability of improved HRQoL at 6 months was reported as 87% for those taking IL-6 RA and 97.4% for antiplatelets.

Several limitations were noted, including a considerable amount of missing data on HRQoL and disability outcomes, which were not collected at all sites and could not be collected at baseline as patients were critically ill. Moreover, the results related to the effectiveness of interventions on prior variants of COVID-19 and prior to extensive availability of vaccination, and the effectiveness on newer variants and vaccinated patients is unknown.

The authors noted that among critically ill patients with COVID-19 randomized to receive one or more therapeutic interventions, treatment with an IL-6 RA 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,” the authors concluded.

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