Clinical trial NCT05200754: Trial With or Without Infusion of SARS-CoV-2 Antibody Containing Plasma in High-Risk Patients With COVID-19
Official title: A Randomized Open Label Phase-II Clinical Trial With or Without Infusion of Plasma From Subjects After Convalescence of SARS-CoV-2 Infection in High-Risk Patients With Confirmed Severe SARS-CoV-2 Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: SARS-CoV-2 Infection
Keywords: High risk patients
convalescent plasma
post vaccination plasma
COVID-19
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
name: Institut für Klinische Transfusionsmedizin und Zelltherapie Heidelberg gGmbH
First posted: 2022-01-21
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The study RECOVER is a randomized, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent/vaccine-boosted plasma or standard of care.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Improvement
timeFrame: within 84 days
Secondary outcomes:
measure: Overall survival rate
timeFrame: within 84 days
measure: Viral clearance
timeFrame: within 84 days
measure: Cytokine profiles
timeFrame: within 84 days
measure: Antibody titres
timeFrame: within 84 days
measure: Requirement of mechanical ventilation
timeFrame: within 84 days
measure: Discharge from hospital
timeFrame: within 84 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universtitätsmedizin Berlin
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte - Klinik für Innere Medizin I
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz Medizinische Klinik III
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt Medizinische Klinik II
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I
city: Essen
country: Germany
facility: Universitätsklinikum Essen Klinik für Infektiologie
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt Medizinische Klinik II
city: Frankfurt/Oder
country: Germany
facility: Klinikum Frankfurt (Oder) - Medizinische Klinik I
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Allgemeine Infektion-Ambulanz / Klinik für Innere Medizin II
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf Zentrum für Innere Medizin I
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg Innere Medizin V
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg - Studienzentrum Pneumologie
city: Herford
country: Germany
facility: Klinikum Herford
city: Leverkusen
country: Germany
facility: Klinikum Leverkusen - Medizinische Klinik 3
city: Meschede
country: Germany
facility: Klinikum Hochsauerland
city: Münster
country: Germany
facility: Universitätsklinikum Münster Medizinische Klinik B
Study officials:
affiliation: University Hospital Heidelberg
name: Carsten Mueller-Tidow, Prof. Dr.
role: STUDY_DIRECTOR
References: