Convalescent Plasma for the Treatment of Patients With Severe COVID-19 Infection

Convalescent Plasma for the Treatment of Patients With Severe COVID-19 Infection - A Multicenter Phase II Trial

This is a multicenter, Phase 2 study, to assess the efficacy of the treatment with convalescent plasma in patients with severe COVID-19 infection.

Study Overview

• Status: Recruiting
• Conditions: COVID-19 Infection
• Intervention / Treatment: Procedure: Convalescent Plasma

Detailed Description

Convalescent plasma will be collected by plasmapheresis from patients fully recovered from COVID-19 infection and will be administered in patients with severe COVID-19 infection. The results will be compared with an historical matched control.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aikaterini Niarchou; Phone Number: +30 6949124743; Email: aniarchou@med.uoa.gr
• Study Contact Backup: Name: Ioanna Charitaki; Phone Number: +30 6976156403; Email: j.charitaki@gmail.com

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece, 10676
      • Recruiting
      • "Evangelismos" General Hospital
    • Athens, Attiki, Greece, 115 22
      • Recruiting
      • "Agios Savas" Oncology Hospital
    • Athens, Attiki, Greece, 115 28
      • Recruiting
      • "Alexandra" General Hospital
    • Athens, Attiki, Greece, 11527
      • Recruiting
      • "Sotiria" General Hospital
  • Chaidari
    • Athens, Chaidari, Greece, 124 62
      • Recruiting
      • Attikon" University General Hospital
  • Rio
    • Patra, Rio, Greece, 26504
      • Recruiting
      • University General Hospital of Patras

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. Age >18 years
2. Confirmed SARS-CoV2 infection by PCR of the nasal/pharyngeal swab, sputum, BAL
3. Onset of the disease symptoms no more than 12 days before the inclusion of the patients in the trial

4. Severe COVID-19 infection as determined with one of the following:

   • Respiratory rate 30/min
   • Oxygen Hemoglobin Saturation SAT 93
   • CRP >1.5 (upper normal limit <0.5)
   • Ferritin value >100
   • Ratio of PaO2:FiO2 <300mmHg
   • Pulmonary infiltrates in Chest X-Ray or Chest CT scan >50% during 24-48 hours

5. Life threatening infection as determined by one of the following:

   • Respiratory failure
   • Septic Shock
   • Multiple organ failure
6. Signature of informed consent by the patient or legal representative Patients fulfilling criteria 1, 2, 3, 6 and one of criteria 4 or 5 will be eligible for the study.

Exclusion Criteria:

1. Critical illness due to progressive COVID-19 with expected survival time <48 hours
2. Intubated patients >72 hours
3. Chronic Heart failure NYHA 3 and/or preexisting left ventricular ejection fraction 30%
4. Cardiovascular failure requiring 0.5μg/Kg/min nor-adrenaline or equivalent or more than 2 types of vasopressor medication
5. Liver Cirrhosis Child C
6. Liver failure with bilirubin >5X ULN and increase of ALT/AST (at least one >10X ULN)
7. Previous history of allergic reaction to blood or blood products transfusion
8. Known IgA deficiency
9. Pregnancy
10. Breast feeding women
11. Pulmonary edema

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Convalescent Plasma; Convalescent Plasma - early treatment of patients with severe COVID-19

Procedure: Convalescent Plasma; Convalescent Plasma - early treatment of patients with severe COVID-19. Clinical and laboratory data of patients will be collected before initiation of the procedure, 30 minutes after the first dose, 30 minutes after the second dose and 30 minutes after the third plasma dose and then on days 1-7, 14, 21, 28, 35 from the start of treatment. In case of adverse reactions during transfusion such as acute shortness of breath, haemodynamic instability or high pre-existing and non-disease-related fever, the transfusion will be interrupted and detailed recording of the event as well as updating the Adverse Events Management Committee will be performed. In addition to the standard assessments, the titer of neutralizing anti-SARS-CoV-2 antibodies will be measured in a sample drawn prior to plasmapheresis. All donors will be tested for: the titer of IgG anti-SARS-CoV-2 antibodies (Pasteur Institute); the titer of neutralizing anti-SARS-CoV-2 antibodies (Pasteur Institute)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	The primary endpoint of this trial is the survival on day 21. The primary endpoint, as a dichotomous composite of survival (yes/no) and no longer fulfilling criteria of severe COVID-19, will be analyzed according their classification. Specifically, categorical variables will be analyzed by means of absolute and relative frequencies, and all continuous variables will be described using arithmetic mean, standard deviation, median, quartiles. Also, geometric means, variance and 95% confidence intervals (CI), will be calculated for all pharmacokinetics parameters.	Day 21
Survival	The primary endpoint of this trial is the survival on day 35.	Day 35
Survival	The primary endpoint of this trial is the survival on day 60.	Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement ie percentage of patients not fulfilling the criteria for severe disease	The secondary endpoint of this trial is that no longer fulfilling criteria of severe COVID-19 within 21 days after inclusion. This will be assessed on the basis of respiratory rate and ventilation support.	Day 21

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: Hellenic Society of Hematology
• Investigators: Principal Investigator: Meletios Athanasios Dimopoulos, National and Kapodistrian University of Athens; Study Chair: Evangelos Terpos, MD, National and Kapodistrian University of Athens

Publications and helpful links

General Publications

• Pappa V, Bouchla A, Terpos E, Thomopoulos TP, Rosati M, Stellas D, Antoniadou A, Mentis A, Papageorgiou SG, Politou M, Kotanidou A, Kalomenidis I, Poulakou G, Jahaj E, Korompoki E, Grigoropoulou S, Hu X, Bear J, Karaliota S, Burns R, Pagoni M, Trontzas I, Grouzi E, Labropoulou S, Stamoulis K, Bamias A, Tsiodras S, Felber BK, Pavlakis GN, Dimopoulos MA. A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis. Microorganisms. 2021 Apr 11;9(4):806. doi: 10.3390/microorganisms9040806.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Anticipated): August 30, 2023
• Study Completion (Anticipated): December 15, 2023

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Actual): September 27, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: 245-14-4-20

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