Official Title
Convalescent Plasma Therapy From Recovered Covid-19 Patients as Therapy for Hospitalized Patients With Covid-19
Brief Summary

Passive immunization with immunoglobulins is occasionally used as therapy for the treatment of viral infectious diseases. Immunoglobulins are used for the treatment of CMV disease, and is effective as prophylaxis when given soon after exposure to varicella zoster virus, rabies, and hepatitis B virus. Neutralizing antibodies against MERS, SARS-CoV-1 and SARS-CoV-2 have been shown to be present in patients previously infected with MERS, SARS-CoV-1 and SARS-CoV-2 respectively. During the 2003 SARS outbreak in Hong-Kong,a non-randomized study in hospitalized SARS patients showed that treatment with convalescent plasma (convP) from SARS-recovered donors significantly increased the day 22 discharge rate and decreased mortality. A study in non-human primates showed that rhesus macaques could not be re-infected with SARS-CoV-2 after primary infection. With no proven effective therapy against COVID, this study will evaluate the safety and efficacy of convalescent plasma from COVID-recovered donors as a treatment for hospitalized patients with symptomatic COVID-19. The study will focus on patients who tested positive for SARS-CoV-2 in the last 96 hours before inclusion Primary objectives • Decrease overall mortality in patients within COVID disease Study design: This trial is a randomized comparative trial. Patients will be randomized between the infusion of 300mL of convP with standard of care. Patient population: Patients with PCR confirmed COVID disease, age >18 years Donors will be included with a known history of COVID who have been asymptomatic for at least 14 days. Intervention: 300mL of convP Duration of treatment: ConvP will be given as a one-time infusion Duration of follow up: For the primary endpoint: until discharge or death before day 60, whichever comes first. For the secondary endpoints (with separate consent) up to 1 year. Target number of patients: 426 Target number of donors: 100 Expected duration of accrural: 36 months

Detailed Description

Secondary (exploratory) objectives

- Evaluate the effect of 300ml convP on hospital stay

- Evaluate the change of the 8-point WHO COVID19 disease severity scale on day 15 and 30

- Evaluate the change of the 8-point WHO COVID19 disease severity scale on day 15 in the
subgroup of patients with a baseline neutralizing antibody titer (PRNT50) <80

- Evaluate the effect of 300ml convP on mortality in patients admitted to the ICU

- Evaluate the effect of 300ml plasma therapy on hospital days for patients admitted to
the ICU within 24 hours after admission

- Evaluate the impact of plasma therapy on the decrease in SARS-CoV2 shedding from airways

- Evaluate the difference in effect of convP on mortality in patients with a duration of
symptoms < or > the median duration of symptoms in the study population

- Evaluate the impact of CTL and NK cell immunity on the likelihood of being protected
from immune serum transfer

- Safety of convP therapy

- Evaluate the impact of covP on long-term lung function


Biological: Convalescent plasma

Infusion of plasma retrieved from donors with a history of PCR proven symptomatic COVID.
Plasma will be administered according to the Erasmus MC KIS protocol regarding the use of blood products

Eligibility Criteria

Inclusion Criteria:

- Patients with PCR confirmed COVID disease

- Admitted to the hospital

- The most recent PCR positive sample is <96hrs old

- Written informed consent by patient or legal patient representative

- Age at least 18 years

Exclusion Criteria:

- Participation in another intervention trial on the treatment of COVID-19 that falls
under the Dutch law human research (WMO) and in which individual patients are
randomized to different treatment options

- Known IgA deficiency

- Invasive ventilation for already >96 hours

Donors: Eligibility for plasma donation

Inclusions Criteria:

- A history of COVID infection that was documented by PCR

- Known ABO-Resus(D) blood group

- A screening for irregular antibodies with a titer ≤ 1:32

- Asymptomatic for at least 14 days

- Written informed consent regarding the plasmapheresis procedure

- Tested negative for HIV, HBV, HCV, HEV, HTLV and syfilis

Exclusion Criteria:

- Age <18 years and > 65 years

- Weight <50kg

- Medical history of heart failure

- History of transfusion with red blood cells, platelets or plasma

- History of organ- or tissue transplant

- A cumulative stay in the United Kingdom of ≥ 6 months in the period between 01-01-1980
and 31-12-1996

- A history of i.v. drug use

- Insulin dependent diabetes

- An underlying severe chronic illness (i.e. history of heart failure, cancer or stroke)

- Tested positive for HLA- or HNA-antibodies

Eligibility Gender
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A

Erasmus Medical Center
Rotterdam, Zuid-Holland, Netherlands

NoordWest Ziekenhuisgroep
Alkmaar, Netherlands

Onze Lieve Vrouwen Gasthuis
Amsterdam, Netherlands

Rijnstate Ziekenhuis
Arnhem, Netherlands

Reinier de Graaf Gasthuis
Delft, Netherlands

Haaglanden Medisch Centrum
Den Haag, Netherlands

Catharina Ziekenhuis
Eindhoven, Netherlands

Medisch Spectrum Twente
Enschede, Netherlands

Groene Hart Ziekenhuis
Gouda, Netherlands

Martini Hospital
Groningen, Netherlands

Spaarna Gasthuis
Haarlem, Netherlands

Alrijne Ziekenhuis
Leiderdorp, Netherlands

Sint Antonius Ziekenhuis
Nieuwegein, Netherlands

Canisius-Wilhelmina Hospital
Nijmegen, Netherlands

Maasstad Ziekenhuis
Rotterdam, Netherlands

ZorgSaam Hospital
Terneuzen, Netherlands

Bernhoven Hospital
Uden, Netherlands

Venlo, Netherlands

Bart Rijnders, MD, PhD, Principal Investigator
Erasmus Medical Center

Prothya Biosolutions
NCT Number
MeSH Terms