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

February 21, 2022 updated by: Paola Maria Manzini, Azienda Ospedaliera Città della Salute e della Scienza di Torino

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Torino, Italy, 10126
        • AO Città della Salute e della Scienza di Torino

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: 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.
Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee
EXPERIMENTAL: STP + Standard Plasma (SP)
STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee
Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP
EXPERIMENTAL: 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 according to the best evidence treatment recommended by the Regional Health System emergency committee
Transfusion of three SARS-Cov-2 neutralizing antibodies positive Plasma Units (CP) on day 1,3,5 in addition to STP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30-days survival
Time Frame: 30 days after randomization
Proportion of patients alive 30 days after randomization
30 days after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilator free survival
Time Frame: 30 days after randomization
Cumulative incidence of mechanical ventilation or death
30 days after randomization
6-months survival
Time Frame: 6 months after randomization
Probability of being alive at 6 months after randomization
6 months after randomization
Incidence of complications
Time Frame: Within 12 months
Proportion of patients developing any serious medical or procedure related complications
Within 12 months
Days in intensive care units (ICU)
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
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
Positivity for Immunoglobulin G to 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
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
Clearance of viral load
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
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
Sequential Organ Failure Assessment (SOFA) score
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
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
Any variation 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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Paola Maria Manzini, MD, AO Città della Salute e della Scienza di Torino

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 15, 2020

Primary Completion (ACTUAL)

March 31, 2021

Study Completion (ACTUAL)

October 31, 2021

Study Registration Dates

First Submitted

June 7, 2020

First Submitted That Met QC Criteria

June 10, 2020

First Posted (ACTUAL)

June 11, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 23, 2022

Last Update Submitted That Met QC Criteria

February 21, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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