Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

Abstract

Background. Convalescent plasma (CP) therapy in COVID-19 disease has been suggested to improve clinical outcome in severe disease. This pilot study was designed to inform the design of a definitive phase 3 clinical trial. Methods. This was a prospective, interventional and randomized open label pilot trial involving 40 patients with COVID-19 who were requiring oxygen therapy and who had radiological evidence of pneumonia. Twenty COVID-19 patients received two 200ml transfusions of convalescent patient CP over 24 hours were compared with 20 patients who received routine care alone. The primary outcome was the requirement for ventilation. The secondary outcomes were white blood cell count, lactate dehydrogenase (LDH), C-reactive protein (CRP), Troponin, Ferritin, D-Dimer, procalcitonin, mortality rate at 28 days. Results. The CP group were a higher risk group with higher ferritin levels (p<0.05) though respiratory indices did not differ. The primary outcome measure (ventilation) was required in 6 controls and 4 patients on CP (risk ratio 0.67 95% CI 0.22 to 2.0, p=0.72); mean time on ventilation was 10.5 days in the control against 8.2 days in patients on CP (p=0.81). There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. Conclusion. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy though fewer patients required ventilation and for a shorter period of time. The study showed that CP therapy appears to be safe and it is feasible to perform a definitive phase 3 clinical trial using this study protocol.

Mortality Benefit of Convalescent Plasma in COVID-19: A Systematic Review and Meta-Analysis

“…Similarly, 37 studies (11,12,(55)(56)(57)(58)(59)(60)(61)(62) reported the adverse event rate in COVID-19 patients on plasma therapy, as shown in Figure 4. A total of 21,668 patients with CPT were included in the analysis, of which a total of 1,506 patients had adverse events.…”

“…We performed a subgroup analysis 2C). However, during the sensitivity analysis of 10 randomized trials (28,31,34,42,56,(58)(59)(60)(61)(62), no statistically significant reduction of COVID-19 deaths was shown (OR 0.76, 95% CI 0.53-1.08, p = 0.13, I 2 = 7%) (Figure 2D). Agarwal et al (28) demonstrated a different effect and had a large statistical weight (34.3%).…”

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

“…In ten other reported randomised trials, including a total of 1495 patients hospitalised with COVID-19, 218 of whom died, convalescent plasma was associated with a non-significant reduction in mortality (rate ratio 0•77, 95% CI 0•57-1•04; p=0•08; figure 4). [11][12][13][14][15][16][17][18][19][20] After inclusion of the results from RECOVERY (which includes nearly eight-times as many patients and more than 11-times as many events as the other trials combined) into this Favours convalescent plasma Favours usual care AlQahtani et al (2020) 16 Bajpai et al (2020) 15 Avendaño-Solà et al (2020) 19 Balcells et al (2020) 17 Gharbharan et al (2020) 14 Li et al (2020) 11 Ray et al (2020) 18 O'Donnell et al (2021) 20 Simonovich et al (2021) 13 Agarwal et al (2020…”

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

“…A total of 74 studies 2, 5, 15-18, 36-39, 41-44, 47-54, 56, 57, 59-63, 65-67, 69, 70, 72, 74-76, 78, 79, 82, 83, 85, 87, 88, 90-92, 94-97, 99, 100, 103-121, 125 including 48622 patients reported all-cause mortality. After filtering out treatments with small sample size following the specified criteria, the network included azithromycin, hydroxychloroquine, hydroxychloroquine plus azithromycin, colchicine, arbidol (umifenovir), favipiravir, remdesivir, lopinavir/ritonavir, convalescent plasma, methylprednisolone, dexamethasone, hydrocortisone, immunoglobulin, interferon beta, recombinant human granulocyte colony-stimulating factor (GCSF), tocilizumab, vitamin D 3 , baricitinib plus remdesivir, sulodexide and SOC.…”

“…Overall, 48 studies reported the number of patients required for MV during the study period. 2, 5, 15-17, 36-39, 41-44, 47-50, 56, 57, 60-63, 65, 69, 72, 76, 78, 82, 83, 87, 92, 95-97, 100, 103-105, 108-110, 112-114, 116, 117, 120 with 41405 patients and 4455 events. We included azithromycin, hydroxychloroquine, hydroxychloroquine plus azithromycin, remdesivir, lopinavir/ritonavir, convalescent plasma, methylprednisolone, dexamethasone, hydrocortisone, immunoglobulin, interferon beta, recombinant human GCSF, tocilizumab, vitamin D 3 , baricitinib plus remdesivir, sulodexide and SOC as treatment nodes in the NMA.…”