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

SARS-CoV-2 Infection Clinical Trial

— RECOVER  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05200754
• Other study ID #: SARS-CoV-2CP-HD-001
• Status: Recruiting
• Phase: Phase 2
• Start date: September 3, 2020
• Est. completion date: June 2022

Study information

• Verified date: January 2022
• Source: University Hospital Heidelberg
• Contact: Carsten Mueller-Tidow, Prof. Dr.
• Phone: +49 6221-56 8001
• Email: carsten.mueller-tidow[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: June 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Infections
• SARS-CoV-2 Infection

Intervention

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.

Locations

Country	Name	City	State
Germany	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	Thoraxklinik Heidelberg - Studienzentrum Pneumologie	Heidelberg
Germany	Universitätsklinikum Heidelberg Innere Medizin V	Heidelberg
Germany	Klinikum Herford	Herford
Germany	Klinikum Leverkusen - Medizinische Klinik 3	Leverkusen
Germany	Klinikum Hochsauerland	Meschede
Germany	Universitätsklinikum Münster Medizinische Klinik B	Münster

Sponsors (3)

Lead Sponsor	Collaborator
Carsten Müller-Tidow	German Federal Ministry of Education and Research, Institut für Klinische Transfusionsmedizin und Zelltherapie Heidelberg gGmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Improvement	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	within 84 days
Secondary	Overall survival rate	Overall survival and overall survival rate at 28, 56 and 84 days	within 84 days
Secondary	Viral clearance	SARS-CoV-2 viral clearance and load	within 84 days
Secondary	Cytokine profiles	Cytokine changes over time	within 84 days
Secondary	Antibody titres	Measurement of antiviral antibody titres	within 84 days
Secondary	Requirement of mechanical ventilation	Percentage of patients that required mechanical ventilation	within 84 days
Secondary	Discharge from hospital	Time from randomization until discharge	within 84 days