Efficacy and Safety of COVID-19 Convalescent Plasma

• ClinicalTrials.gov Identifier: NCT04397523
• Recruitment Status: Completed
• First Posted: May 21, 2020
• Last Update Posted: May 11, 2021
• Sponsor: Institute for Transfusion Medicine of RNM
• Collaborator: University Clinic for Infectious Diseases, North Macedonia
• Information provided by (Responsible Party): Institute for Transfusion Medicine of RNM

Tracking Information

• First Submitted Date: May 20, 2020
• First Posted Date: May 21, 2020
• Last Update Posted Date: May 11, 2021
• Actual Study Start Date: April 30, 2020
• Actual Primary Completion Date: May 10, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2020)

• Duration of oxygenation and ventilation support [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  The total number of days patients required respiratory support.
• Hospital length of stay (LOS) [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Total number of days patients were admitted to the hospital.
• ICU admission [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Total number of subjects to be admitted to the ICU after the convalescent plasma transfusion.
• Ventilator free days [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Days without oxygenation support after receiving convalescent plasma
• Incidence of serious adverse events [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Cumulation incidence of serious adverse events during the study protocol

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 20, 2020)

• Type of respiratory support [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Type of supplemental oxygen support (e.g. nasal canula, high flow nasal canula, noninvasive ventilation, intubation and invasive mechanical ventilation, rescue ventilation)
• Number of participants with different clinical outcomes including death, critical illness and recovery [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Number of participants with different clinical outcomes including death, critical illness and recovery

Original Secondary Outcome Measures (submitted: May 20, 2020)

• Type of respiratory support [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Type of supplemental oxygen support (e.g. nasal canula, high flow nasal canula, noninvasive ventilation, intubation and invasive mechanical ventilation, rescue ventilation)
• Clinical outcome [ Time Frame: 28 days after transfusion or until hospital discharge (whichever comes first) ]
  Number of participants with different clinical outcomes including death, critical illness and recovery

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of COVID-19 Convalescent Plasma
• Official Title: Use of COVID-19 Convalescent Plasma in the Patients Infected With COVID-19 (SARS-CoV-2) - Efficacy and Safety
• Brief Summary: Administration of convalescent plasma obtained from donors with prior documented SARS-CoV-2 infection
• Detailed Description: There are currently no proven therapeutic options for coronavirus disease (COVID-19), the infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human convalescent plasma is an option for treatment of COVID-19. Experience from prior outbreaks with other coronaviruses, such as SARS-CoV-1, MERS and H1N1 shows that convalescent plasma can be effective. Convalescent plasma will be obtained by plasmapheresis or regular whole blood donation in subjects who recovered from COVID-19 and who are otherwise eligible for donation according to the Institutional protocol. Recipients will be COVID-19 patients requiring hospitalization. A blood-type matched transfusion of convalescent plasma will be infused and recipients will be followed up.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Convalescent Plasma
• COVID-19
• SARS-CoV 2

Intervention

Biological: anti-SARS-CoV-2 convalescent plasma

Administration of convalescent plasma obtained from donors with prior documented SARS-CoV-2 infection

Study Arms

Hospitalized patients with SARS CoV-2 infection

Hospitalized patients with SARS CoV-2 infection will receive an anti SARS-CoV-2 convalescent plasma

Intervention: Biological: anti-SARS-CoV-2 convalescent plasma

Publications *

• Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr;20(4):398-400. doi: 10.1016/S1473-3099(20)30141-9. Epub 2020 Feb 27.
• Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.
• Huaxia, (2020). 'China puts 245 COVID-19 patients on convalescent plasma therapy', Xinhua.net, 2 February. Available at: http://www.xinhuanet.com/english/2020-02/28/c_138828177.htm
• Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 Apr 1;130(4):1545-1548. doi: 10.1172/JCI138003.
• Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19: Possibilities and Challenges. JAMA. 2020 Apr 28;323(16):1561-1562. doi: 10.1001/jama.2020.4940.
• https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-deviceexemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds Accessed on March 30,2020
• Guidance on collection, testing, processing, storage, distribution and monitored use. An EU programme of COVID-19 convalescent plasma collection and transfusion. EUROPEAN COMMISSION DIRECTORATE-GENERAL FOR HEALTH AND FOOD SAFETY, 08 April, 2020
• AABB's CCP Collection Protocol - Donor Eligibility, Processing, Labeling and Distribution, 03 April, 2020 http://www.aabb.org/advocacy/regulatorygovernment/Documents/COVID-19-Convalescent-Plasma-Collection.pdf

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 25, 2021): 200
• Original Estimated Enrollment (submitted: May 20, 2020): 20
• Actual Study Completion Date: May 10, 2021
• Actual Primary Completion Date: May 10, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

Blood donors:

1. Age: >18 and <60 years
2. Body weight : >55 kg
3. Confirmed previous SARS CoV-2 infection
4. Minimum 28 days after the last symptom or finishing of the isolation, or
5. 21 day without symptoms from the date of the negative SARS CoV-2 test
6. Written informed consent to participate in this clinical trial, to donate plasma and to store the specimen for future testing.
7. Concentration of COVID-19 IgG antibodies more than 5 AU/ml (Because measurement of neutralizing antibody titers is not available now, storing of retention sample from the convalescent plasma donation is performed for determining antibody titers at a later date)
8. Male donors, or female donors who have not been pregnant, or female donors who have been pregnant tested negative for HLA antibodies
9. Individuals who meet all regular voluntary donor eligibility requirements

Patients/recipients:

1. Age: >18 years
2. Admitted to an acute care facility for the treatment of COVID-19 complications
3. Patients with severe or immediately life-threatening COVID-19, or
4. Patients who are judged by a healthcare provider to be at high risk of progression to severe or life-threatening disease.
5. Informed consent provided by the patient or healthcare proxy

Exclusion Criteria:

Blood donors:

1. Age : <18 or >60 years
2. Female subjects who are pregnant
3. HIV1,2 hepatitis B,C or syphilis infection
4. Donors ineligible for regular voluntary blood donation

Patients/recipients:

1. Age : <18 years
2. Contraindication to transfusion (severe volume overload, history of anaphylaxis to blood products)
3. Patients who received in the past 30 days immunoglobulin therapy
4. Females who are pregnant or breastfeeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: North Macedonia

Administrative Information

• NCT Number: NCT04397523
• Other Study ID Numbers: ITM05/2020MKD
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Institute for Transfusion Medicine of RNM
• Study Sponsor: Institute for Transfusion Medicine of RNM
• Collaborators: University Clinic for Infectious Diseases, North Macedonia

Investigators

• Principal Investigator: Rada Grubovic Rastvorceva, MD MSci PhD; Institute for Transfusion Medicine of RNM
• Principal Investigator: Sedulla Useini, MD; Institute for Transfusion Medicine of RNM

• PRS Account: Institute for Transfusion Medicine of RNM
• Verification Date: February 2021