Hospitalized patients with mild SARS-CoV-2 infection (WHO R&D Blueprint Ordinal Scale for Clinical Improvement = 3 or 4) MedDRA version: 23.0 Level: LLT Classification code 10084272 Term: SARS-CoV-2 infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Fresh frozen plasma (FFP) with marketing authorisation in Germany issued by PEI
Product Name: Gefrorenes Apherese-COVID-19-RKP Leukozytendepletiert
Pharmaceutical Form: Solution for infusi
Sponsors
Hannover Medical School
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients infected with SARS-CoV-2 virus and 1. age = 18 years and = 75 years 2. fulfills RKI case definition including a positive verification of a SARS-CoV-2 infection from any specimen (e.g. respiratory, blood, other bodily fluid)* * confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap) 3. mild disease defined by the following criteria: - Hospitalized (score 3 or 4 of WHO R&D Blueprint ordinal scale for clinical improvement) 4. signed written informed consent and willingness to comply with treatment and follow-up procedures 5. ? men; or ? women without childbearing potential defined as follows: • at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy, • hysterectomy or uterine agenesis, • = 50 years and in postmenopausal state > 1 year, or • 1 year with serum FSH > 40 IU/l and serum estrogen =65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 1. Accompanying diseases other than COVID-19 with an expected survival time of less than 12 months 2. In the opinion of the clinical team, progression to death is imminent and inevitable with-in the next 24 hours, irrespective of the provision of treatment 3. Chronic obstructive lung disease (COPD), stage 4 4. Lung fibrosis with UIP pattern in CT und severe emphysema 5. Chronic heart failure NYHA >= 3 and/or pre-existing reduction of left ventricular ejection fraction to = 30% 6. Liver cirrhosis Child C 7. Liver failure: Bilirubin > 5xULN and elevation of ALT /AST (at least one >10xULN). 8. End stage renal failure requiring hemodialysis 9. Organ or bone marrow transplant in the three month prior to screening 10. History of adverse reactions to plasma proteins 11. Known deficiency of immunoglobulin A 12. Pregnancy and breastfeeding women 13. Volume overload until sufficiently treated 14. Pulmonary edema 15. Body mass index (BMI) > 40 kg/m2 16. Participation in another clinical trial, especially for treatment of COVID-19 17. Allergy or other contraindication to one of the investigational products 18. Previous treatment with SARS-CoV-2 convalescent plasma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of convalescent plasma for the treatment of hospitalized patients with mild COVID-19 infection;Secondary Objective: To evaluate the safety and tolerability of experimental regimen;Primary end point(s): Proportion of patients with treatment failure on day 14. A treatment failure is defined as pro-gression of COVID-19 disease. Progression is defined as score 5, 6, 7 or 8 of WHO R&D Blueprint ordinal scale for clinical improvement.;Timepoint(s) of evaluation of this end point: Day 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Failure rates at day 7, day 21, day 28 2. Time to clinical improvement (defined as time from randomization to an improvement of two points on the WHO R&D Blueprint ordinal scale for clinical improvement) 3. Adverse events 4. All-cause mortality (ACM) on day 7, day 14, day 21, day 28, 4 months 5. Length of hospital stay 6. Deterioration in health (progressive disease) 7. Need of ventilation support / additional organ support, e.g. ECMO 8. Time until virus clearance from body sites (negative SARS-CoV-2 PCR in nasopharyngeal sample) 9. Predictive value of comorbidities and inflammation and coagulation markers on clinical improvement, mortality, length of hospital stay and necessity of transfer to ICU 10. Feasibility of collection of plasma units from donors who recovered from a SARS-CoV-2 infection 11. Level of identity of kinetics of anti-SARS-CoV-2 antibodies in plasma of patients compared to plasma of donors (Kinetics of antibodies detectable in the patient after convalescent plasma treatment, Pharmacokinetic parameters: The maximum observed anti-SARS-CoV-2 (Cmax), and the time to Cmax (tmax) will be determined directly from the anti-SARS-CoV-2 versus time data. The observed titer at the end of a dosing interval (Ctrough) will also be determined directly from the anti-SARS-CoV-2 versus time data. Calculated parameters [apparent terminal phase elimination rate constant (b), terminal phase elimination half-life (t1/2), and the area under the curve (AUC)] will be estimated using non compartmental analysis with PK-Sim software. Accumulation ratios will be calculated based on the AUC values of the consecutive dosing intervals and the Cmax values of the consecutive dosing intervals.) 12. Titer of neutralizing anti-SARS-CoV-2 in transfused plasma units 13. Impact of donor characteristics on humoral response against anti-SARS-CoV-2 (age; gender; severity of COVID-19; interval between resolution of symptoms and plasmapheresis). 14. Course of ant | — |
Countries
Germany
Contacts
Public ContactInstitute of Transfusion Medicine
Hannover Medical School
Outcome results
None listed