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

COVID-19 Clinical Trial

— PLACO-COVID  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04428021
• Other study ID #: CS3/33
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2020
• Est. completion date: October 31, 2021

Study information

• Verified date: February 2022
• Source: Azienda Ospedaliera Città della Salute e della Scienza di Torino
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: October 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Respiratory Insufficiency

Intervention

Drug:
• Standard Therapy Protocol (STP)
Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee

Other:
• STP + Standard Plasma (SP)
Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP
• STP + 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

Locations

Country	Name	City	State
Italy	AO Città della salute e della scienza di Torino	Torino

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Città della Salute e della Scienza di Torino

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30-days survival	Proportion of patients alive 30 days after randomization	30 days after randomization
Secondary	Ventilator free survival	Cumulative incidence of mechanical ventilation or death	30 days after randomization
Secondary	6-months survival	Probability of being alive at 6 months after randomization	6 months after randomization
Secondary	Incidence of complications	Proportion of patients developing any serious medical or procedure related complications	Within 12 months
Secondary	Days in intensive care units (ICU)	Proportion of days spent in ICU on the total length of hospital stay	From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months
Secondary	Positivity for Immunoglobulin G to SARS-Cov-2	Proportion of patients showing seroconversion to Immunoglobulin G (IgG) anti-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
Secondary	Clearance of viral load	Proportion of patients showing viral clearance by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) on plasma and respiratory tract samples	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
Secondary	Sequential Organ Failure Assessment (SOFA) score	Variations in SOFA Score (range 0-24; higher score mean a worse outcome)	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
Secondary	Any variation from Standard Therapy Protocol	Proportion of patients needing introduction of new drug or discontinuation of drug 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