Standard or Convalescent Plasma in Patients With Recent Onset of COVID-19 Respiratory Failure (PLACO-COVID)
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Standard Therapy Protocol (STP)
STP + Standard Plasma (SP)
STP + COVID-19 Convalescent Plasma (CP)
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
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
Sites / Locations
- AO Città della salute e della scienza di Torino
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Standard therapy protocol (STP)
STP + Standard Plasma (SP)
STP + COVID-19 Convalescent Plasma (CP)
Arm Description
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 + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies
Outcomes
Primary Outcome Measures
30-days survival
Proportion of patients alive 30 days after randomization
Secondary Outcome Measures
Ventilator free survival
Cumulative incidence of mechanical ventilation or death
6-months survival
Probability of being alive at 6 months after randomization
Incidence of complications
Proportion of patients developing any serious medical or procedure related complications
Days in intensive care units (ICU)
Proportion of days spent in ICU on the total length of hospital stay
Positivity for Immunoglobulin G to SARS-Cov-2
Proportion of patients showing seroconversion to Immunoglobulin G (IgG) anti-SARS-Cov-2
Clearance of viral load
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
Variations in SOFA Score (range 0-24; higher score mean a worse outcome)
Any variation from Standard Therapy Protocol
Proportion of patients needing introduction of new drug or discontinuation of drug from standard therapy protocol
Full Information
NCT ID
NCT04428021
First Posted
June 7, 2020
Last Updated
February 21, 2022
Sponsor
Azienda Ospedaliera Città della Salute e della Scienza di Torino
1. Study Identification
Unique Protocol Identification Number
NCT04428021
Brief Title
Standard or Convalescent Plasma in Patients With Recent Onset of COVID-19 Respiratory Failure
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
June 15, 2020 (Actual)
Primary Completion Date
March 31, 2021 (Actual)
Study Completion Date
October 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliera Città della Salute e della Scienza di Torino
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Three arms randomized trial, partially blinded
Masking
ParticipantCare ProviderOutcomes 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
Allocation
Randomized
Enrollment
180 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard therapy protocol (STP)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
STP + Standard Plasma (SP)
Arm Type
Experimental
Arm Description
STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
Arm Title
STP + COVID-19 Convalescent Plasma (CP)
Arm Type
Experimental
Arm Description
STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies
Intervention Type
Drug
Intervention Name(s)
Standard Therapy Protocol (STP)
Intervention Description
Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee
Intervention Type
Other
Intervention Name(s)
STP + Standard Plasma (SP)
Intervention Description
Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP
Intervention Type
Other
Intervention Name(s)
STP + COVID-19 Convalescent Plasma (CP)
Intervention Description
Transfusion of three SARS-Cov-2 neutralizing antibodies positive Plasma Units (CP) on day 1,3,5 in addition to STP
Primary Outcome Measure Information:
Title
30-days survival
Description
Proportion of patients alive 30 days after randomization
Time Frame
30 days after randomization
Secondary Outcome Measure Information:
Title
Ventilator free survival
Description
Cumulative incidence of mechanical ventilation or death
Time Frame
30 days after randomization
Title
6-months survival
Description
Probability of being alive at 6 months after randomization
Time Frame
6 months after randomization
Title
Incidence of complications
Description
Proportion of patients developing any serious medical or procedure related complications
Time Frame
Within 12 months
Title
Days in intensive care units (ICU)
Description
Proportion of days spent in ICU on the total length of hospital stay
Time Frame
From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months
Title
Positivity for Immunoglobulin G to SARS-Cov-2
Description
Proportion of patients showing seroconversion to Immunoglobulin G (IgG) anti-SARS-Cov-2
Time Frame
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
Title
Clearance of viral load
Description
Proportion of patients showing viral clearance by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) on plasma and respiratory tract samples
Time Frame
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
Title
Sequential Organ Failure Assessment (SOFA) score
Description
Variations in SOFA Score (range 0-24; higher score mean a worse outcome)
Time Frame
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
Title
Any variation from Standard Therapy Protocol
Description
Proportion of patients needing introduction of new drug or discontinuation of drug from standard therapy protocol
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paola Maria Manzini, MD
Organizational Affiliation
AO Città della salute e della scienza di Torino
Official's Role
Principal Investigator
Facility Information:
Facility Name
AO Città della salute e della scienza di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All Individual Participant Data requests should be submitted to the corresponding author for consideration. Access to deidentified participant data may be granted following review, after the publication of major results
IPD Sharing Time Frame
Data will be available after 12 months from study ending and for the following 5 years
IPD Sharing Access Criteria
Data requests should be submitted to the corresponding author for consideration.
Learn more about this trial
Standard or Convalescent Plasma in Patients With Recent Onset of COVID-19 Respiratory Failure
We'll reach out to this number within 24 hrs