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

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

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.

Study Overview

• Status: Recruiting
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Other: Convalescent/Vaccine-boosted Plasma (CP/PVP)

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 Type: Interventional
• Enrollment (Anticipated): 174
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carsten Mueller-Tidow, Prof. Dr.; Phone Number: +49 6221-56 8001; Email: carsten.mueller-tidow@med.uni-heidelberg.de
• Study Contact Backup: Name: Claudia Denkinger, PD Dr.; Phone Number: +49 6221- 56 22999; Email: claudia.denkinger@med.uni-heidelberg.de

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité Universtitätsmedizin Berlin
    • Contact: Lars Bullinger, Prof. Dr.
  • Bremen, Germany, 28205
    • Recruiting
    • Klinikum Bremen-Mitte - Klinik für Innere Medizin I
    • Contact: Bernd Hertenstein, Prof. Dr.
  • Chemnitz, Germany, 09116
    • Recruiting
    • Klinikum Chemnitz Medizinische Klinik III
  • Darmstadt, Germany, 64283
    • Recruiting
    • Klinikum Darmstadt Medizinische Klinik II
    • Contact: Carl Schimanski, Prof. Dr.
  • Dresden, Germany, 01307
    • Recruiting
    • Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I
    • Contact: Nael Alakel, Dr. med.
  • Essen, Germany, 45147
    • Recruiting
    • Universitätsklinikum Essen Klinik für Infektiologie
    • Contact: Oliver Witzke, Prof. Dr.
  • Frankfurt am Main, Germany, 60590
    • Recruiting
    • Universitätsklinikum Frankfurt Medizinische Klinik II
    • Contact: Timo Wolf, PD Dr.
  • Frankfurt/Oder, Germany, 15236
    • Recruiting
    • Klinikum Frankfurt (Oder) - Medizinische Klinik I
    • Contact: Olaf Hopfer, Dr. med.
  • Freiburg, Germany, 79106
    • Recruiting
    • Universitätsklinikum Freiburg, Allgemeine Infektion-Ambulanz / Klinik für Innere Medizin II
    • Contact: Winfried Kern, Prof. Dr.
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf Zentrum für Innere Medizin I
    • Contact: Stefan Schmiedel, Dr. med.
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitätsklinikum Heidelberg Innere Medizin V
    • Contact: Carsten Mueller-Tidow, Prof. Dr.; Phone Number: +49 6221 56 8001; Email: carsten.mueller-tidow@med.uni-heidelberg.de
  • Heidelberg, Germany, 69126
    • Recruiting
    • Thoraxklinik Heidelberg - Studienzentrum Pneumologie
    • Contact: Felix Herth, Prof. Dr.
  • Herford, Germany, 32049
    • Recruiting
    • Klinikum Herford
    • Contact: Matthias Ruhe, Dr. med.
  • Leverkusen, Germany, 51375
    • Not yet recruiting
    • Klinikum Leverkusen - Medizinische Klinik 3
    • Contact: Utz Krug, Prof. Dr.
  • Meschede, Germany, 59872
    • Recruiting
    • Klinikum Hochsauerland
    • Contact: Mohammad- Amen Wattad, Dr. med.
  • Münster, Germany, 48149
    • Recruiting
    • Universitätsklinikum Münster Medizinische Klinik B
    • Contact: Phil-Robin Tepasse, Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Convalescent/Vaccine-boosted Plasma; Infusion of plasma on day 1 and 2 (238 - 337 ml anti-SARS-Cov-2 CP/PVP each)	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.
No Intervention: Standard of Care; No intervention - standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Carsten Müller-Tidow
• Collaborators: German Federal Ministry of Education and Research; Institut für Klinische Transfusionsmedizin und Zelltherapie Heidelberg gGmbH
• Investigators: Study Director: Carsten Mueller-Tidow, Prof. Dr., University Hospital Heidelberg

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2020
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 7, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; convalescent plasma; High risk patients; post vaccination plasma
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections
• Other Study ID Numbers: SARS-CoV-2CP-HD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No