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

Abstract

Objective To assess the efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. Design, setting, and participants Open-label, randomized clinical trial of intensive care unit (ICU) patients with life-threatening COVID-19 [positive real-time-polymerase-chain-reaction test, plus acute respiratory distress syndrome (ARDS), sepsis, organ failure, hyperinflammation]. The study was terminated after 87/120 patients were enrolled. Intervention and randomization Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by peripheral arterial oxygen saturation/fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio (> 150 versus ≤ 150). Main Outcomes and measures Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in Sequential Organ Function Assessment (SOFA) score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length-of-stay. Results Eighty-seven patients [median years of age 49 (IQR: 34-63); 72 males (82.8%)] were randomized [44 to standard care; 43 to standard care plus TPE]. Days on MV (p=0.007) and ICU length-of-stay (p=0.02) were lower in the TPE group versus controls. Thirty-five-day mortality was lower in the TPE group (20.9% vs. 34.1% in controls), but this did not reach statistical significance [Kaplan-Meir analysis: p=0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity; plus decreased serum lactate, lactate dehydrogenase, ferritin, D-dimers, and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO 2 /FiO 2 ratio [hazard 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), and PE (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) compared to controls. Conclusion In critically ill COVID-19 patients the addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.

What Is the Role of Therapeutic Plasma Exchange as an Adjunctive Treatment in Severe COVID-19: A Systematic Review

“…The most common types of studies were case-series studies ( n = 14) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], then case-control studies ( n = 2) [ 17 , 35 ] and a propensity score matched study [ 36 ]. Only one randomized controlled trial was included in the analysis [ 37 ]. Study selection process is presented on the flowchart ( Figure 1 ).…”

“…Only one study was a randomized controlled trial [ 37 ]. The risk of bias of the study was rated as “low” by implementing the RoB2 tool (randomization process: low risk; deviations from the intended interventions: low risk; missing outcome data: low risk; measurement of the outcome: low risk; selection of the reported results: low risk).…”

“…Out of 384 patients, 220 received TPE. The number of patients in the studies varied from 3 to 90 with a median of 8 patients (IQR 5–18) [ 17 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The mean or the median age of participants in seven studies was below 65 years [ 8 , 10 , 11 , 12 , 13 , 14 , 15 ], whereas in the remaining four studies, it was above 65 years [ 5 , 6 , 7 , 9 ].…”

“…The mean or the median age of participants in seven studies was below 65 years [ 8 , 10 , 11 , 12 , 13 , 14 , 15 ], whereas in the remaining four studies, it was above 65 years [ 5 , 6 , 7 , 9 ]. Information regarding gender was available in all of the studies [ 17 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], of which the majority of patients were male. Only three studies had a similar gender ratio of about 40%–60% [ 22 , 30 , 33 ].…”

“…Only three studies had a similar gender ratio of about 40%–60% [ 22 , 30 , 33 ]. The most common reason to qualify a patient for TPE was acute respiratory distress syndrome (ARDS) ( n = 8 [ 21 , 22 , 23 , 24 , 32 , 33 , 35 , 37 ]). Another frequent inclusion criterion was cytokine release syndrome (CRS) [ 23 , 25 , 36 , 37 ].…”