Negative trials of prone positioning, antiplatelet therapy for COVID-19
Telling inpatients to lay on their stomachs did not significantly improve outcomes, one study found, while others offered some mixed results on the effects of aspirin and P2Y12 inhibitors. Additional research showed that a commonly used triage score doesn't work for COVID-19 and that hospitalists' worry about catching the virus impaired their well-being.
Prone positioning did not help inpatients with moderate hypoxemia due to COVID-19, according to a trial published by The BMJ on March 23. The study was conducted at 15 hospitals in Canada and the U.S. and included 248 patients who were on supplemental oxygen and could follow instructions and reminders to lie on their stomachs while in bed. Patients who received the instructions spent a median of six of their first 72 hours prone (range, 1.5 to 12.8 hours) compared to zero in those receiving usual care (range, 0 to 2 hours). The study was stopped early due to futility because the primary outcome (a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure) occurred at similar rates in the prone and control groups (18 vs. 17 events; odds ratio [OR], 0.92 [95% CI, 0.44 to 1.92]). The authors concluded that their intervention to increase prone positioning did not improve outcomes, but they noted that the study was limited by low adherence to proning and that the wide confidence intervals in the results do not rule out benefit or harm. “The most common reason for the lack of adherence that patients would anecdotally report to research coordinators was discomfort,” they said. “Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning.”
Antiplatelet therapy did not improve outcomes in critically ill adult patients with COVID-19, according to a report from the REMAP-CAP trial, published by JAMA on March 22. Patients were randomized, open label, to aspirin (n=565), a P2Y12 inhibitor (n=455), or no antiplatelet therapy (n=529) in addition to anticoagulation thromboprophylaxis. Enrollment in the trial was discontinued for futility after the two antiplatelet groups showed no difference against each other, or, when pooled, against controls, on the primary outcome of organ support-free days. However, the proportion of patients surviving to hospital discharge was 71.5% in the antiplatelet group versus 67.9% in the control group (median-adjusted OR, 1.27 [95% credible interval, 0.99 to 1.62]; adjusted absolute difference, 5% [95% credible interval, −0.2% to 9.5%]; 97% posterior probability of efficacy). Major bleeding occurred in 2.1% and 0.4% of the groups, respectively. “It is possible that antiplatelet therapy may reduce fatal complications of COVID-19 in critically ill patients while potentially increasing the need for organ support, possibly through bleeding that may or may not be clinically evident, such as alveolar hemorrhage,” the authors said.
An accompanying editorial reviewed the existing research on antithrombotic use in COVID-19, concluding that the data support doing less rather than more. “At this juncture in the global pandemic, all hospitalized patients with COVID-19 and low risk of bleeding should receive at least prophylactic-dose anticoagulation with a heparin anticoagulant, with consideration of therapeutic-dose heparin in some cases, but there is no proven efficacy supporting the addition of traditional antiplatelet therapies to prevent progressive thromboinflammatory complications of COVID-19,” the editorial said.
However, another study, published by JAMA Network Open on March 24, found that early aspirin use was associated with better outcomes among moderately ill patients hospitalized with COVID-19. The observational cohort study included 112,269 patients and found that, after inverse probability treatment weighting, 28-day in-hospital mortality was significantly lower in those who received aspirin (10.2% vs. 11.8%; OR, 0.85 [95% CI, 0.79 to 0.92]; P<0.001), as was the rate of pulmonary embolism (1.0% vs 1.4%; OR, 0.71 [95% CI, 0.56 to 0.90]; P=0.004), leading the authors to conclude that a randomized clinical trial is warranted.
Other recent COVID-19 research found that the Sequential Organ Failure Assessment (SOFA) score does not accurately predict in-hospital mortality in patients requiring mechanical ventilation for COVID-19. The analysis of 15,122 ventilated patients, published by Critical Care Medicine on March 15, found that patient age had greater discriminant accuracy for mortality than the SOFA score. The authors noted that 31 U.S. states feature the SOFA score in their crisis standards of care guidelines for ventilator triage. Finally, a survey of hospitalists and hospital medicine advanced practice clinicians, published by the Journal of Hospital Medicine on March 24, found that concern about contracting COVID-19 at work significantly affected their well-being. “These findings do not establish causality but provide a strong foundation for ongoing wellness efforts,” the authors said.
