The study RECOVER is a randomized, open-label, multicenter phase II trial, designed toassess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group4) following treatment with anti-SARS-CoV-2 convalescent/vaccine-boosted plasma orstandard of care.
The aim of this randomized phase-II study is to gain evidence on the effect of
convalescent plasma/vaccine-boosted plasma in the treatment of SARS-CoV-2 infection in
high-risk patients.
High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at
ambient air with additional risk features as categorized in 4 groups:
- group 1, pre-existing or concurrent hematological malignancy and/or active cancer
therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or
less.
- group 2, chronic immunosuppression not meeting the criteria of group 1
- group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and
at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1μg/mL
- group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2
The duration of the trial for each patient is expected to be about 3 months, including
two days of intervention (infusion of CP/PVP), followed by a follow-up of 3 months.
Furthermore viral load is measured in nasopharagyngeal swabs at day 1, 3, 5, 10, 14, 28
or until hospital discharge within 84 days after randomization. Treatment response is
assessed daily until day 28, thereafter weekly until day 56, and finally at day 84.
Patients randomized into the standard arm of the study have the possibility to cross over
into the experimental arm of the study starting at day 10 (+ 2 days) in case of not
improving or worsening clinical condition.
In total 174 patients are planned to be enrolled in the study.
Other: Convalescent/Vaccine-boosted Plasma (CP/PVP)
Plasma from apheresis obtained from donors, who have recovered from SARS-CoV-2 infection
or received a successful vaccination against SARS-CoV-2.
CP/PVP infusion is administered on two following days. Each CP/PVP bag contains approx.
238 - 337 ml anti-SARS-Cov-2 CP/PVP for infusion.
Inclusion Criteria:
1. PCR confirmed SARS-CoV-2 infection in a respiratory tract sample.
2. Oxygen saturation (SaO2) of 94% or less while breathing ambient air or a ratio of
the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of
less than 300 mm Hg.
3. High risk due to either pre-existing or concurrent hematological malignancy and/or
active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24
months or less (group 1) and/or chronic immunosuppression not meeting the criteria
of group 1 (group 2) and/or Age ≥ 50 -75 years meeting neither the criteria of group
1 nor group 2 (group 3) and at least one of these criteria: Lymphopenia < 0.8 x G/l
and/or D-dimer > 1μg/mL and/or Age ≥ 75 years meeting neither the criteria of group
1 nor group 2 (group 4).
4. Blood hemoglobin concentration ≥ 8 g/dl.
5. Provision of written informed consent.
6. Patient is able to understand and comply with the protocol for the duration of the
study, including treatment and scheduled visits and examinations.
7. Male or female patient aged ≥ 18 years
8. Postmenopausal or evidence of non-childbearing status. For women of childbearing
potential: negative urine or serum pregnancy test within 14 days prior to study
treatment.
Exclusion Criteria:
1. Dementia, psychiatric or cognitive illness or recreational drug/alcohol use that in
the opinion of the principle investigator, would affect subject safety and/or
compliance.
2. Contraindication to transfusion or history of prior reactions to transfusion blood
products.
3. Patients with selective IgA deficiency.
4. Patients with mechanical ventilation and/or extracoporal membrane oxygenation (ECMO)
at time of initial inclusion into the trial. Mechanical ventilation is defined as
either NIV - non-invasive ventilation or positive pressure ventilation. Enrollment
into another clinical trial evaluating specific therapies for COVID-19 is
encouraged.
5. Participation in another trial with an investigational medicinal product.
6. Treatment with SARS-CoV-2 convalescent/vaccine-boosted plasma in the past.
Charité Universtitätsmedizin Berlin
Berlin, Germany
Klinikum Bremen-Mitte - Klinik für Innere Medizin I
Bremen, Germany
Klinikum Chemnitz Medizinische Klinik III
Chemnitz, Germany
Klinikum Darmstadt Medizinische Klinik II
Darmstadt, Germany
Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I
Dresden, Germany
Universitätsklinikum Essen Klinik für Infektiologie
Essen, Germany
Universitätsklinikum Frankfurt Medizinische Klinik II
Frankfurt am Main, Germany
Klinikum Frankfurt (Oder) - Medizinische Klinik I
Frankfurt/Oder, Germany
Universitätsklinikum Freiburg, Allgemeine Infektion-Ambulanz / Klinik für Innere Medizin II
Freiburg, Germany
Universitätsklinikum Hamburg-Eppendorf Zentrum für Innere Medizin I
Hamburg, Germany
Universitätsklinikum Heidelberg Innere Medizin V
Heidelberg, Germany
Thoraxklinik Heidelberg - Studienzentrum Pneumologie
Heidelberg, Germany
Klinikum Herford
Herford, Germany
Klinikum Leverkusen - Medizinische Klinik 3
Leverkusen, Germany
Klinikum Hochsauerland
Meschede, Germany
Universitätsklinikum Münster Medizinische Klinik B
Münster, Germany
Carsten Mueller-Tidow, Prof. Dr.
+49 6221-56 8001
carsten.mueller-tidow@med.uni-heidelberg.de
Claudia Denkinger, PD Dr.
+49 6221- 56 22999
claudia.denkinger@med.uni-heidelberg.de
Carsten Mueller-Tidow, Prof. Dr., Study Director
University Hospital Heidelberg