Table 1.

Randomized clinical trials of COVID-19 convalescent plasma

First author or trial name	Country of origin	Trial design	CCParm, N	Control arm, N	Control	Clinical status: severity of COVID-19	No. of days to enrollment from		Primary end point	Efficacy	Comment
							Symptom onset	Admission
PLACID Trial19	India	RCT open label	227	224	Standard of care	Moderate WHO scale 4-5	Median of 4 d (IQR 6-11)	Composite of progression	Composite of progression to severe disease or all-cause mortality by d 28	10% CCP vs 18% control met primary endpoint (RR 1.04; 95% CI (0.71-1.54)	CCP titer varied widely
AlQahtani20	Bahrain	RCT open label	20	20	Standard of care	Moderate WHO scale 4-6	Variable	Variable	Requirement for noninvasive or mechanical ventilation support	6 control and 4 CCP patients reached primary endpoint (RR 0.67, 95% CI 0.22-2.0, P = .72)	N/A
Avendano-Sola31	Spain	RCT open label	38	43	Standard of care	Moderate WHO scale 4-6	Median of 8 d (IQR, 6-9)	N/A	Proportion of patients on noninvasive ventilation or high-flow O2; or on invasive mechanical ventilation or ECMO or death by d 15	0% CCP vs 14% control advanced to mechanical ventilation; mortality rates were 0% CCP vs 9.3% control on d 15 and 29.	Trial did not reach enrollment goal.
CONCOR-1 Study Group13	Canada and USA	RCT open label	614	307	Standard of care	Moderate to severe WHO scale 4-6	8 d (IQR 5-10)	N/A	Composite of intubation or death by d 30	Convalescent plasma did not reduce the risk of intubation or death at 30 d.	Trial terminated at 78% enrollment after meeting stopping criteria for futility.
Bennet-Guerrerro21	USA	RCT double-blind	59	15	Nonimmune plasma	Moderate to severe WHO scale 4-7*	N/A		Total no. of ventilation-free days from randomization to d 28	CCP was not associated with improved outcome.	Enrollment terminated early after emergency use authorization was granted for CCP.
REMAP-CAP Investigators26	Multinational	RCT open label	1084	916	Standard of care	Moderate to severe WHO scale 4-7*	Median of 10 d (IQR 6-15)	From hospital admission, 1.7-1.8; from ICU admission, 17.2-17.7	Organ support-free days to d 21	Endpoint reached for 0 (IQR –1 to 16) for control. Median adjusted OR 0.97 (95% credible interval 0.83-1.15).	The prespecified criteria for futility were met thereby terminating the trial.
Gharbharan22	The Netherlands	RCT open label	43	43	Standard of care	Moderate to severe WHO scale 4-7*	Median of 10 d (IQR 6-15)	Median 2 d (IQR 1-3)	Clinical status on 8-point WHO COVID-19 disease severity score on d 15 and 30	No overall clinical benefit of CCP was observed. CCP had no effect on disease course. CCP did not enhance viral clearance from respiratory tract. CCP did not influence SARS-COV-2 antibody development or serum proinflammatory cytokine levels.	Found that vast majority of patients had neutralizing SARS-COV-2 antibodies at hospital admission. This finding led to early termination of trial.
RECOVERY Trial26	United Kingdom	RCT open label	5795	5763	Standard of care	Moderate to severe WHO scale 4-7*	9 d (6-12)	2 d (1-4)	28-d mortality	No significant difference in primary endpoint in CCP (24%) vs control (24%) groups (rate ratio 1.00, 95% CI 0.93-1.07; P = .95).	The 28-d mortality rate ratio was similar in all prespecified subgroups of patients, including in-patients without detectable SARS-COV-2 antibodies at randomization.
Kirenga27	Uganda	RCT open label	69	67	Standard of care	Moderate to severe WHO scale 4-6	Median of 7 d (IQR 4-8)	N/A	Time to viral clearance	Time to viral clearance was not different between the 2 arms.	N/A
SIREN-C3PO Investigators35	USA	RCT single blind	257	254	Normal saline	Mild WHO scale 2-3	Median of 4 d. Mean of 3.7 ± 2.1 d	N/A	Disease progression within 15 d	Disease progression occurred in 77/257 (30%) of CCP group vs 81/254 (31.9%) of placebo group (risk difference 1.9%; 95% credible interval, –6.0 to 9.8).	Trial enrollment was halted after a planned interim analysis of the primary outcome indicated that the threshold for futility had been reached.
CAPSID Trial28	Germany	RCT open label	53	52	Standard of care	Moderate to severe WHO scale 4-7	Median of 7 d (IQR 4-10)	N/A	Dichotomous composite of survival and no longer fulfilling criteria for severe COVID-19 on d 21	The primary outcome occurred in 43.4% of patients in the CCP and 32.7% of patient in the control group (P = .32).	Patients in the CCP arm received 3 units of high-titer CCP over a period of 5 d.
Li23	China	RCT open label	52	51	Standard of care	Moderate to severe WHO scale 4-7*	Median of 30 d	N/A	Time to clinical improvement within 28 d	51% CCP vs 31% control met primary endpoint (HR 1.40; 95% CI 0.79-2.49; P = .26)	103 of planned 200 enrolled
Libster33	Argentina	RCT double-blind	80	80	Normal saline	Asymptomatic to mild WHO scale 1-2	<72 h	N/A	Severe respiratory disease	16% CCP vs 31% control met primary endpoint (RR 0.52; 95% CI 0.29-0.94; P = .03)	Trial did not reach enrollment goal.
O’Donnell24	USA and Brazil	RCT double-blind	150	73	Nonimmune plasma	Moderate to severe WHO scale 4-9	Control: 9 d (IQR 7-11) CCP: 10 d (IQR 7-13)	N/A	Clinical status at 28 d	No significant improvement in CCP cohort (OR 1.50, 95% CI 0.83-2.68; P = .18.	28-d mortality was significantly lower in CCP cohort vx control (19/150 [12.6%] vs 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91; P = .034).
Salman30	Egypt	RCT open label	15	15	Standard of care	Moderate to severe WHO scale 4-6	8 d CCP cohort; 9 d control group	13 d	At least 50% improvement of the severity of illness at any time during 5 d after transfusion.	In CCP group there was an improvement in 4 signs of symptoms of illness severity within 5-d study period that was significant compared with control group (P < .05).	N/A
PlasmAr Study Group29	Argentina	RCT double-blind	228	105	Normal Saline	Moderate to severe WHO scale 4-6	8 d (IQR 5-10) N/A	N/A	Clinical status 30 d after intervention using WHO 6-point disease severity scale	No significant difference reported between CCP and control cohort in the distribution of clinical outcomes (OR 0.83; 95%, CI 0.52-1.35; P = .46).	N/A

Published RCTs were used that compared CCP with standard of care or placebo; preprints were included for trials with >80 subjects.

IQR, interquartile range; OR, odds ratio; N/A, not applicable.

^*Information was not available to distinguish between WHO scale categories 7 and 9.