A randomized, double blinded clinical trial of convalescent plasma compared to standard plasma for treatment of hospitalized non-ICU patients with COVID-19 infections

This is a randomized, prospective, multicenter, double blinded phase 2/3 trial comparing efficacy and safety of anti-SARS-CoV-2 convalescent plasma vs standard plasma in maximally 3 days hospitalized COVID-19 patients that are not at or bound to be referred to the ICU.

In the described context of possible benefits but still uncertain risks, we on purpose perform a double blinded phase 2/3 RCT to investigate both safety and effectivity of early in the disease course administrated convalescent plasma in patients with COVID-19. The latter patients are sick enough to warrant hospitalization but have not (yet) experienced overwhelming disease including a systemic inflammatory response, sepsis, and/or ARDS warranting ventilation and (eminent) ICU referral.

Study population:
This study will enrol adult patients with confirmed COVID-19 infection, who have been recently (not more than 3 days) hospitalized, but are not admitted to the ICU or expected to go to the ICU within 6 hours of first plasma administration.

Intervention:
Enrolled patients will either receive convalescent thawed fresh frozen plasma 1 unit (250-325 ml) (=treatment group) or standard thawed fresh frozen plasma 1 unit (250-325 ml) (=control group)

Study endpoints:
The estimated benefit in regard of the primary endpoint is a shift in the distribution of the scores towards less mortality, mechanical ventilation, ICU admission and shorter than the presently mean hospital stay (see figure). The primary endpoint will be analyzed using a Bayesian proportional odds model. Posterior probabilities will start to be computed after 20 patients have completed their follow-up and will be computed on regular basis afterwards.
The endpoints can be summarized as following:
= Ordinal outcome of all cause mortality, mechanical ventilation, ICU admission and long duration of hospital stay (6 days or more), with less than 6 hospitalized days as reference category will be used for the primary outcome. The outcome will be primarily assessed at day 14.
- The following other efficacy parameters will be assessed as a secondary outcome: assessment of the primairy ordinal outcome at day 21, 28 and 56; combined outcome of death and ICU admission at day 14, 21, 28 and 56; duration of hospitalization in days; length of stay in ICU; and ICU mortality.
- The following safety parameters will be assessed during this trial: deterioration of respiratory, circulatory or otherwise the clinical status during transfusion; transfusion transmitted infections.
- The time until negative SARS-CoV-2 PCR (nasal/ pharyngeal swab)

Convalescent plasma of ex-COVID-19 patients will improve outcome of recently admitted patients with active disease but not (yet) at ICU.

days 1,2,3,7,14,21,28,56

Enrolled patients will either receive convalescent thawed fresh frozen plasma 1 unit (250-325 ml) (=treatment group) or standard thawed fresh frozen plasma 1 unit (250-325 ml) (=control group)