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Standard or Convalescent Plasma in Patients With Recent Onset of COVID-19 Respiratory Failure

Phase 2
Completed
Conditions
COVID-19
Interventions
Drug: Standard Therapy Protocol (STP)
Other: STP + COVID-19 Convalescent Plasma (CP)
Other: STP + Standard Plasma (SP)
Registration Number
NCT04428021
Lead Sponsor
A.O.U. Città della Salute e della Scienza
Brief Summary

To date no specific treatment has been proven to be effective for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) infection. It is possible that convalescent plasma that contains antibodies to SARS-Cov-2 might be effective against the progression of infection. Promising results have been shown by preliminary data from China cases. The investigators planned to compare effectiveness of adding COVID-19 convalescent plasma to standard therapy protocol (STP) versus adding plasma donated in pre-COVID era versus STP alone in patient with COVID-19 within 5 days from the onset of respiratory distress. STP at enrolment is the best evidence based therapy approved for treatment of COVID patients by regional Health system emergency committee.

Detailed Description

500-700 ml of Plasma will be collected by apheresis from COVID recovered donors showing the presence of neutralizing antibodies to SARS-Cov-2 (anti-SARS-Cov-2). All plasma will be screened for transmissible diseases according to italian law (Hepatitis B Virus,Hepatitis C Virus, Human Immunodeficiency Virus 1-2, Syphilis) plus adjunctive screening for Hepatitis A Virus and Hepatitis E Virus-RNA and Parvovirus B19-DNA as requested from Italian National Blood Authority. Apheresis will be divided in two/three units (170-300 ml each), virus inactivated with Riboflavin and ultraviolet light illumination technology and immediately frozen and stored separately from other plasma bags.

Enrolled patients will be stratified according to severity of respiratory failure and randomized in three arms: 1) Standard Therapy Protocol (STP), 2) Standard Therapy Protocol + 170-350 ml standard Plasma (SP) on day 1-3-5 after randomization, 3) Standard Therapy Protocol + 170-350 ml COVID-19 Convalescent Plasma on day 1-3-5 after randomization.

The three therapeutic units of COVID-19 Convalescent plasma will be chosen in order to minimize variations among patients in the total amount of infused SARS-Cov-2 antibodies.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
180
Inclusion Criteria
  • Confirmed SARS-Cov-2 diagnosis by RT-PCR on nasopharyngeal swab or on bronchoalveolar lavage
  • Respiratory failure onset or progression within 5 days
  • Signed Informed Consent
Exclusion Criteria
  • Pregnancy
  • Previous severe reactions to plasma transfusion
  • Unavailability of blood group compatible COVID-19 convalescent plasma

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
STP + Standard Plasma (SP)Standard Therapy Protocol (STP)STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
STP + COVID-19 Convalescent Plasma (CP)STP + COVID-19 Convalescent Plasma (CP)STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies
Standard therapy protocol (STP)Standard Therapy Protocol (STP)STP is defined as the best evidence based therapy approved for treatment of COVID-19 patients by Regional Health System emergency committee. STP could be updated during the trial.
STP + Standard Plasma (SP)STP + Standard Plasma (SP)STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
STP + COVID-19 Convalescent Plasma (CP)Standard Therapy Protocol (STP)STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies
Primary Outcome Measures
NameTimeMethod
30-days survival30 days after randomization

Proportion of patients alive 30 days after randomization

Secondary Outcome Measures
NameTimeMethod
Clearance of viral loadOn day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months

Proportion of patients showing viral clearance by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) on plasma and respiratory tract samples

Ventilator free survival30 days after randomization

Cumulative incidence of mechanical ventilation or death

Sequential Organ Failure Assessment (SOFA) scoreOn day 0, 2, 4, 6, 10, 14, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months

Variations in SOFA Score (range 0-24; higher score mean a worse outcome)

Incidence of complicationsWithin 12 months

Proportion of patients developing any serious medical or procedure related complications

6-months survival6 months after randomization

Probability of being alive at 6 months after randomization

Days in intensive care units (ICU)From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months

Proportion of days spent in ICU on the total length of hospital stay

Positivity for Immunoglobulin G to SARS-Cov-2On day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months

Proportion of patients showing seroconversion to Immunoglobulin G (IgG) anti-SARS-Cov-2

Any variation from Standard Therapy ProtocolFrom date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed daily up to 2 months

Proportion of patients needing introduction of new drug or discontinuation of drug from standard therapy protocol

Trial Locations

Locations (1)

AO Città della salute e della scienza di Torino

🇮🇹

Torino, Italy

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