COVID-19
Conditions
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.
Interventions
DRUGStandard Therapy Protocol (STP)
Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee
OTHERSTP + Standard Plasma (SP)
Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP
OTHERSTP + COVID-19 Convalescent Plasma (CP)
Transfusion of three SARS-Cov-2 neutralizing antibodies positive Plasma Units (CP) on day 1,3,5 in addition to STP
Sponsors
A.O.U. Città della Salute e della Scienza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Only the two experimental arms are masked. COVID-19 convalescent plasma (CP) and standard plasma (SP) will be masked and delivered to the wards in identical bags; a tag printed as PLASMA TRIAL will cover the actual name of the product
Intervention model description
Three arms randomized trial, partially blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30-days survival | 30 days after randomization | Proportion of patients alive 30 days after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator free survival | 30 days after randomization | Cumulative incidence of mechanical ventilation or death |
| 6-months survival | 6 months after randomization | Probability of being alive at 6 months after randomization |
| Incidence of complications | Within 12 months | Proportion of patients developing any serious medical or procedure related complications |
| Positivity for Immunoglobulin G to SARS-Cov-2 | On 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 |
| Clearance of viral load | On 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 |
| Sequential Organ Failure Assessment (SOFA) score | On 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) |
| Any variation from Standard Therapy Protocol | From 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 |
| 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 |
Countries
Italy
Outcome results
None listed