Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial

Abstract

Assessment of efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. This was an open-label, randomised clinical trial of ICU patients with life-threatening COVID-19 (positive RT-qPCR plus ARDS, sepsis, organ failure, hyperinflammation). Study was terminated after 87/120 patients enrolled. Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by PaO₂/FiO₂ ratio (>150 vs. ≤150), were compared. Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in SOFA score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length of stay (LOS). Eighty-seven patients [median age 49 (IQR 34-63) years; 82.8% male] were randomised (44 standard care; 43 standard care plus TPE). Days on MV (P = 0.007) and ICU LOS (P = 0.02) were lower in the TPE group. 35-Day mortality was non-significantly lower in the TPE group (20.9% vs. 34.1%; Kaplan-Meier, P = 0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity and decreased serum lactate, lactate dehydrogenase, ferritin, d-dimers and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO₂/FiO₂ ratio (HR, 0.98, 95% CI 0.96-1.00; P = 0.02]; ADAMTS-13 activity (HR, 0.89, 95% CI 0.82-0.98; P = 0.01); pulmonary embolism (HR, 3.57, 95% CI 1.43-8.92; P = 0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (P < 0.05). In critically-ill COVID-19 patients, addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.

Keywords: Acute respiratory distress syndrome; COVID-19; Cytokine release syndrome; Intensive care unit; Therapeutic plasma exchange; Thromboinflammation.

Fig. 1

Flow diagram of the randomised clinical trial.

Fig. 2

Kaplan–Meier survival distributions in the intervention and control groups of critically-ill COVID-19 patients (log-rank test, P = 0.582; Cox regression model, HR = 0.81, 95% CI 0.35–1.87, P = 0.62). HR, hazard ratio; CI, confidence interval.

Fig. 3

Post-hoc (repeated measures) analysis of Sequential Organ Function Assessment (SOFA) score (median values with 95% CI) over time (days post ICU admission) for the intervention and control groups of critically ill COVID-19 patients. CI, confidence interval; ICU, intensive care unit.