Trial With or Without Infusion of SARS-CoV-2 Antibody Containing Plasma in High-Risk Patients With COVID-19

Phase 2

• Conditions: SARS-CoV-2 Infection
• Interventions: Other: Convalescent/Vaccine-boosted Plasma (CP/PVP)

• Registration Number: NCT05200754
• Lead Sponsor: Carsten Müller-Tidow

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.

Study Timeline

• Study Start: 2020-09-03
• Status Verified: 2022-01
• Study First Submitted: 2022-01-20
• Study First Submitted QC: 2022-01-20
• Study First Posted: 2022-01-21
• Last Update Submitted: 2022-01-21
• Last Update Posted: 2022-02-07
• Primary Completion: 2022-04
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 174

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Convalescent/Vaccine-boosted Plasma	Convalescent/Vaccine-boosted Plasma (CP/PVP)	Infusion of plasma on day 1 and 2 (238 - 337 ml anti-SARS-Cov-2 CP/PVP each)

Primary Outcome Measures

Name	Time	Method
Clinical Improvement	within 84 days	Time from randomization until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital

Secondary Outcome Measures

Name	Time	Method
Overall survival rate	within 84 days	Overall survival and overall survival rate at 28, 56 and 84 days
Cytokine profiles	within 84 days	Cytokine changes over time
Viral clearance	within 84 days	SARS-CoV-2 viral clearance and load
Discharge from hospital	within 84 days	Time from randomization until discharge
Antibody titres	within 84 days	Measurement of antiviral antibody titres
Requirement of mechanical ventilation	within 84 days	Percentage of patients that required mechanical ventilation

Trial Locations

Locations (16)

Klinikum Darmstadt Medizinische Klinik II; 🇩🇪 Darmstadt, Germany

Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I; 🇩🇪 Dresden, Germany

Universitätsklinikum Freiburg, Allgemeine Infektion-Ambulanz / Klinik für Innere Medizin II; 🇩🇪 Freiburg, Germany

Klinikum Herford; 🇩🇪 Herford, Germany

Universitätsklinikum Münster Medizinische Klinik B; 🇩🇪 Münster, Germany

Klinikum Hochsauerland; 🇩🇪 Meschede, Germany

Universitätsklinikum Hamburg-Eppendorf Zentrum für Innere Medizin I; 🇩🇪 Hamburg, Germany

Universitätsklinikum Essen Klinik für Infektiologie; 🇩🇪 Essen, Germany

Klinikum Frankfurt (Oder) - Medizinische Klinik I; 🇩🇪 Frankfurt/Oder, Germany

Charité Universtitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Klinikum Bremen-Mitte - Klinik für Innere Medizin I; 🇩🇪 Bremen, Germany

Klinikum Chemnitz Medizinische Klinik III; 🇩🇪 Chemnitz, Germany

Universitätsklinikum Frankfurt Medizinische Klinik II; 🇩🇪 Frankfurt am Main, Germany

Universitätsklinikum Heidelberg Innere Medizin V; 🇩🇪 Heidelberg, Germany

Klinikum Leverkusen - Medizinische Klinik 3; 🇩🇪 Leverkusen, Germany

Thoraxklinik Heidelberg - Studienzentrum Pneumologie; 🇩🇪 Heidelberg, Germany