Table 1 Ongoing randomised controlled trials of convalescent plasma in COVID-19 illness assessed using the PICO framework. These RCTs were identified in a recent Cochrane review by Valk et al. [4]. Participants: We report the setting (severely ill/critically ill versus general wards). In high-risk non-ventilated patients (high inspired oxygen, and/or non-invasive ventilation), this could reduce the need for mechanical ventilation. In ventilated patients, this may translate into improved mortality and reduced length of critical care stay. Intervention: For intervention, we report the description of convalescent plasma volume and titres if highlighted. In SARS-1 patients, convalescent plasma improved outcomes when administered within 14 days of illness onset and in those without detectable antibodies against coronavirus at the time of infusion. Only four studies use a predetermined neutralising titre cutoff with convalescent plasma. Comparator: We highlight whether the ordinary plasma or standard of care was chosen. In five RCTs, the comparator is ordinary plasma transfusion, which may enhance blinding but comes with risks of blood product. When summarising the ongoing current trials, it is unlikely that an efficacy signal would be generated from many of these trials due their methodological limitations (such as small sample size) and biological limitations (such as lack of pre-defined cutoff for neutralising antibody titres). For outcome, we list only the primary outcome for the trial. We also highlight the proposed sample size in the trial.
Trial ID [country] | Participants | Intervention | Comparator | Outcome | N |
|---|---|---|---|---|---|
ChiCTR2000029757 [China] | Severely ill/critically ill | Volume = NR | Standard of care | 2-point improvement in clinical symptoms in a 6-point scale | 200 |
Titres = NR | |||||
ChiCTR2000030010 [China] | Severely ill adults less than 70 years | Volume = NR | Ordinary plasma | 2-point improvement in clinical symptoms in a 6-point scale | 100 |
Titres = NR | |||||
ChiCTR2000030179 [China] | Severely ill adults less than 66 years | Volume = NR | Standard of care | Cure rate | 100 |
Titres = NR | Mortality | ||||
ChiCTR2000030627 [China] | Severely ill/critically ill | Volume = NR | Standard of care | Temperature control | 30 |
Titres = NR | |||||
ChiCTR2000030702 [China] | Hospitalised patients | Volume = NR | Standard of care | Time to clinical recovery after randomisation | 50 |
Titres = NR | |||||
ChiCTR2000030929 [China] | Severely ill adults less than 70 years | Volume = NR | Ordinary plasma | 2-point improvement in clinical symptoms in a 6-point scale | 60 |
Titres = NR | |||||
EUCTR2020-001310-38 [Germany] | Severely ill/critically ill adults less than 75 years | Volume = up to 960 ml | Standard of care | Composite endpoint: - Survival and no longer fulfilling criteria of severe COVID-19 within 21 days after randomisation | 120 |
Titres = NR | |||||
IRCT20200310046736N1 [Iran] | Adult (20 to 45 years) | Volume = 800 ml | Standard of care | N/A | 45 |
Titres = NR | |||||
IRCT20200404046948N1 [Iran] | Severely ill/critically ill adults less than 70 years | Volume = up to 500 ml | Standard of care | 2-point improvement in clinical symptoms at 14 days | 60 |
Titres = NR | |||||
IRCT20200409047007N1 [Iran] | Critically ill adults 50–75 years with Pao2/FIO2 ratio < 300; normal IgA level and within 7 days of admission | Volume = up to 500 ml | Standard of care | 1-month mortality | 35 |
Titres = NR | |||||
IRCT20200413047056N1 [Iran] | Severely ill/critically ill adults less than 50 years | Volume = up to 400 ml | Standard of care or intravenous immunoglobulin | NR | 15(1:1:1) 3-arm study |
Titres = NR | |||||
NCT04332835 [Columbia] | Hospitalised adults less than 60 years | Volume = up to 500 ml | Hydroxychloroquine | Change in viral load | 60 |
Titres = NR | Change in antibody titres | ||||
Coadministration of hydroxychloroquine | |||||
NCT04333251 [USA] | Hospitalised adults | Volume = 2 doses | Standard of care | Reduction in oxygen and ventilation support | 115 |
Titres = > 1:64 | |||||
NCT04342182 [Netherlands] | Hospitalised adults | Volume = up to 300 ml | Standard of care | Mortality | 426 |
Titres = NR | |||||
NCT04344535 [USA] | Hospitalised adults | Volume = up to 550 ml | Standard plasma | Ventilator-free days up to day 28 | 500 |
Titres = > 1:320 | |||||
NCT04345289 [Denmark] | Hospitalised adults with pneumonia | Volume = 600 ml | Multiple interventions; adaptive platform trial | Composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days | 1500 |
Titres = NR | 1:1:1:1:1:1 | ||||
NCT04345523 [Spain] | Hospitalised adults with pneumonia | Volume = 800 ml | Standard of care | WHO ordinal scale | 278 |
Titres = NR | |||||
NCT04345991 [France] | Mild severity as described in the WHO scale, within 8 days | Volume = 800 ml | Standard of care | Survival without needs of ventilator utilisation or use of immunomodulatory drugs at 14 days | 120 |
Titres = NR | |||||
NCT04346446 [India] | Severely ill/critically ill adults less than 65 years | Volume = up to 600 ml | Standard of care | Proportion of patients remaining free of mechanical ventilation at 7 days | 40 |
Titres = NR | |||||
NCT04348656 [Canada] | Hospitalised adults receiving supplemental oxygen | Volume = up to 500 ml | Standard of care | Intubation or hospital mortality within 30 days | 1200 |
Titres = NR | |||||
NCT04355767 [USA] | Adults requiring emergency department evaluation | Volume = up to 600 ml | Standard plasma | Time to disease progression at 15 days | 206 |
Titres = > 1:80 | |||||
NCT04356534 [Bahrain] | Adults > 21 years with severely ill with radiological evidence of pneumonia | Volume = up to 600 ml | Standard of care | Requirement for invasive ventilation | 40 |
Titres = > 1:80 | |||||
NCT02735707 [Multinational] | Severely ill/critically ill adults | Volume = up to 600 ml | Multiple interventions; adaptive platform trial | Days alive and outside of ICU at 21 days | 7100 platform |
Titres = > 1:64 |