Clinical trial NCT04428021: Standard or Convalescent Plasma in Patients With Recent Onset of COVID-19 Respiratory Failure
Official title: Effectiveness of Adding Standard Plasma or COVID-19 Convalescent Plasma to Standard Treatment, Versus Standard Treatment Alone, in Patients With Recent Onset of COVID-19 Respiratory Failure. A Randomized, Three-arms, Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: A.O.U. Città della Salute e della Scienza
Sponsor class: OTHER
First posted: 2020-06-11
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three arms randomized trial, partially blinded
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 30-days survival
timeFrame: 30 days after randomization
Secondary outcomes:
measure: Ventilator free survival
timeFrame: 30 days after randomization
measure: 6-months survival
timeFrame: 6 months after randomization
measure: Incidence of complications
timeFrame: Within 12 months
measure: Days in intensive care units (ICU)
timeFrame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months
measure: Positivity for Immunoglobulin G to SARS-Cov-2
timeFrame: 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
measure: Clearance of viral load
timeFrame: 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
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: 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
measure: Any variation from Standard Therapy Protocol
timeFrame: 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
Other outcomes:
Locations:
city: Torino
country: Italy
facility: AO Città della salute e della scienza di Torino
Study officials:
affiliation: AO Città della salute e della scienza di Torino
name: Paola Maria Manzini, MD
role: PRINCIPAL_INVESTIGATOR
References: