A randomized, prospective, open label clinical trial on the use of convalescent plasma compared to best supportive care in patients with severe COVID-19

INTERVENTION: Trade Name: Fresh frozen plasma (FFP) with marketing authorisation in Germany issued by PEI Product Name: For example "Gefrorenes Frischplasma / Apherese DRK Blutspendedienst" Pharmaceutical Form: Solution for infusion CONDITION: Patients with SARS‐CoV‐2 infection and: 1. age = 18 years and = 75 years 2. SARS‐CoV‐2 infection confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap) 3. severe disease defined by at least one of the following: a. respiratory rate = 30 breaths / minute under ambient air b. requirement of any type of ventilation support c. needs ICU treatment ; MedDRA version: 20.1 Level: LLT Classification code 10047475 Term: Viral pneumonia, unspecified System Organ Class: 100000004862 ; MedDRA version: 23.0 Level: LLT Classification code 10070267 Term: SARS virus test positive System Organ Class: 100000004848 ; MedDRA version: 20.0 Level: LLT Classification code 10021433 Term: Immunization System Organ Class: 100000004865 ; MedDRA version: 21.1 Level: LLT Classification code 10054540 Term: Passive immunization System Organ Class: 100000004865 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: To improve survival ; ; AND; ; remove criteria of severe COVID‐19 (CoV‐2 infection) within 21 days after randomization Primary end point(s): Composite endpoint of:; ; ‐ Survival ; ; AND; ; ‐ no longer fulfilling criteria of severe COVID‐19 within 21 days after randomization; ; All criteria must be met in order to fulfill the primary endpoint.; Secondary Objective: ‐ Time to clinical improvement on WHO R&D Blueprint seven‐category ordinal scale by 2 ; ‐ Adverse events ; ‐ Case fatality rate on days 21, 35 and 60; ‐ Length of hospital stay; ‐ Length of ICU stay ; ‐ Duration of ventilation Support / ECMO; ‐ Time until negative SARS‐CoV‐2 PCR; ‐ Predictive value of comorbidities and inflammation markers ; ‐ Feasibility of collection of plasma units ; ‐ Kinetics of anti‐SARS‐CoV‐2 antibodies in plasma of patients = plasma donors who recovered ; from a SARS‐CoV‐2 infection; ‐ Titer of anti‐SARS‐CoV‐2 in transfused plasma units; ‐ Impact of donor characteristics on anti‐SARS‐CoV‐2 humoral response; ‐ Course of anti‐SARS‐CoV‐2 titer in patients ; ‐ Effect of timing of plasma transfusions on outcome; Timepoint(s) of evaluation of this end point: Treatment group: Day 21; ; Control group: Days 14 and 21 SECONDARY OUTCOME: Secondary end point(s): ‐ Time to clinical improvement on WHO R&D Blueprint seven‐category ordinal scale by 2 ; ‐ Adverse events ; ‐ Case fatality rate on days 21, 35 and 60 ; ‐ Length of hospital stay ; ‐ Length of ICU stay ; ‐ Duration of ventilation Support / ECMO ; ‐ Time until negative SARS‐CoV‐2 PCR ; ‐ Predictive value of comorbidities and inflammation markers ; ‐ Feasibility of collection of plasma units ; ‐ Kinetics of anti‐SARS‐CoV‐2 antibodies in plasma of patients = plasma donors who recovered ; from a SARS‐CoV‐2 infection ; ‐ Titer of anti‐SARS‐CoV‐2 in transfused plasma units ; ‐ Impact of donor characteristics on anti‐SARS‐CoV‐2 humoral response ; ‐ Course of anti‐SARS‐CoV‐2 titer in patients ; ‐ Effect of timing of plasma transfusions on outcome ; ; Cross‐over group: Prior to transfusion of convalescent plasma on days 15, 17 and 19 and one day after infusion (days 16, 18 and 20) and every week thereafter up to day 35. INCLUSION CRITERIA: Patients with SARS‐CoV‐2 infection and: 1. age = 18 years and = 75 years 2. SARS‐CoV‐2 infection confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap) ; Timepoint(s) of evaluation of this end point: Treatment group: Prior to transfusion of convalescent plasma on days 1, 3 and 5 and one day after infusion (days 2, 4 and 6) and every week thereafter up to day 21. 3. severe disease defined by at least one of the following: a. respiratory rate = 30 breaths / minute under ambient air b. requirement of any type of ventilation support c. needs ICU Treatment 4. Written informed consent by patient or legally authorized representative Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 88 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32