Strengths and limitations of this study
Background
Methods
Study objectives and endpoints
Trial design and participants
Patient and public involvement
Recruitment and selection of convalescent donors
Plasma collection from the selected donors
Assessment of the neutralizing antibodies in the donated plasma
Study intervention and procedures
Participant or legal representative consent, inclusion and randomization process
Study arms
Evaluation visits
Procedures | Visits | ||||||||
---|---|---|---|---|---|---|---|---|---|
Screening | Inclusion | Treatment phase | Follow-up | ||||||
Day 1 | Day 7 | Day 14 | Day 21 | Day 28 | ICU Discharge | Day 90 | Day 365 | ||
Informed consent | x | ||||||||
Eligibility assessment | x | x | |||||||
Randomisation | x | ||||||||
Medical history | x | ||||||||
Comorbidities | |||||||||
Prior medications | |||||||||
APACHE II score | x | ||||||||
SOFA score | x | x | x | x | x | ||||
WHO disease progression scale | x | x | x | ||||||
CRP | x | x | x | x | x | ||||
Viral load (NP or tracheal PCR) | |||||||||
Clinical frailty scale | x | ||||||||
Concomitant drugs against SARS-CoV-2 | x | x | x | x | x | x | |||
Biological findings | xa | xb | xb | x b | xb | ||||
24 h-diuresis | x | x | x | x | x | ||||
Serum sample for central analysis | x | x | x | x | |||||
Mechanical ventilation | x | x | x | x | x | ||||
Renal replacement therapy | x | x | x | x | x | ||||
Vasoactive drugs | x | x | x | x | x | ||||
ECMO | x | x | x | x | x | ||||
Nosocomial infections | x | x | x | x | x | ||||
Iatrogenic events | x | x | x | x | x | ||||
Adverse events & Serious adverse event | x | x | x | x | x | ||||
ADL scale | x | x | x | ||||||
Anxiety-depression scale | x | x | |||||||
EQ-5D-5L scale | x | x | x |
Data sharing
Data management and monitoring
Adverse events
Statistical analysis
Sample size
Statistical analysis plan
Interim analysis plan
Interim analysis | Number of patients | Recommend stopping for futility if difference in mortality is smaller than | Recommend stopping for efficacy if difference in mortality is greater than |
---|---|---|---|
1 | 100 | 0.02 (P > 0.83) | - |
2 | 200 | 0.04 (P > 0.60) | 0.22 (P < 0.001) |
3 | 300 | 0.06 (P > 0.28) | 0.14 (P < 0.007) |
4 | 400 | 0.08 (P > 0.12) | 0.11 (P < 0.022) |
5 (final) | 500 | - | 0.09 (P < 0.042) |