COVID-19Phase 2PLACO-COVIDNCT04428021
Standard or Convalescent Plasma in Patients With Recent Onset of COVID-19 Respiratory Failure
A Phase 2 study testing Standard Therapy Protocol (STP), STP + Standard Plasma (SP) and STP + COVID-19 Convalescent Plasma (CP) in people with COVID-19, run by A.O.U. Città della Salute e della Scienza at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Standard Therapy Protocol (STP), STP + Standard Plasma (SP) and STP + COVID-19 Convalescent Plasma (CP)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteItaly
- Study dates
- 15 Jun 2020to 31 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Pregnancy
- Previous severe reactions to plasma transfusion
- Unavailability of blood group compatible COVID-19 convalescent plasma
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Standard Therapy Protocol (STP), STP + Standard Plasma (SP), STP + COVID-19 Convalescent Plasma (CP)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Therapy Protocol (STP)Drug
Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee
STP + Standard Plasma (SP)Other
Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP
STP + COVID-19 Convalescent Plasma (CP)Other
Transfusion of three SARS-Cov-2 neutralizing antibodies positive Plasma Units (CP) on day 1,3,5 in addition to STP
| Study group | Role | What they receive |
|---|---|---|
| Standard therapy protocol (STP) | Active comparator | 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. Receives: Drug: Standard Therapy Protocol (STP) |
| STP + Standard Plasma (SP) | Experimental | STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019) Receives: Drug: Standard Therapy Protocol (STP); Other: STP + Standard Plasma (SP) |
| STP + COVID-19 Convalescent Plasma (CP) | Experimental | STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies Receives: Drug: Standard Therapy Protocol (STP); Other: STP + COVID-19 Convalescent Plasma (CP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
30-days survival
Proportion of patients alive 30 days after randomization
Measured: 30 days after randomization
Secondary outcomes (8)
Ventilator free survival
Cumulative incidence of mechanical ventilation or death
Measured: 30 days after randomization
6-months survival
Probability of being alive at 6 months after randomization
Measured: 6 months after randomization
Incidence of complications
Proportion of patients developing any serious medical or procedure related complications
Measured: Within 12 months
Days in intensive care units (ICU)
Proportion of days spent in ICU on the total length of hospital stay
Measured: 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
Proportion of patients showing seroconversion to Immunoglobulin G (IgG) anti-SARS-Cov-2
Measured: 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
Proportion of patients showing viral clearance by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) on plasma and respiratory tract samples
Measured: 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
Variations in SOFA Score (range 0-24; higher score mean a worse outcome)
Measured: 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
Proportion of patients needing introduction of new drug or discontinuation of drug from standard therapy protocol
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start15 Jun 2020
- Primary completion31 Mar 2021
- Study completion31 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Three arms randomized trial, partially blinded
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- A.O.U. Città della Salute e della Scienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paola Maria Manzini, A.O.U. Città della Salute e della Scienza
- Investigators
- Paola Maria Manzini, MD, Principal investigator, AO Città della salute e della scienza di Torino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04428021
- Sponsor's protocol ID
- CS3/33
- Acronym
- PLACO-COVID
- Status last verified
- Feb 2022
- First submitted
- 7 Jun 2020
- Last updated
- 23 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Manzini PM, Ciccone G, De Rosa FG, Cavallo R, Ghisetti V, D'Antico S, Galassi C, Saccona F, Castiglione A, Birocco N, Francisci T, Hu H, Pecoraro C, Danielle F, Labanca L, Bordiga AM, Lorenzi M, Camisasca G, Giachino O, Pagliarino M, Ottone P, Scuvera ITD, Guaschino R, Freilone R, Berti P, Pittaluga F, Avolio M, Costa C, Raso S, Nucci A, Milan M, Baffa A, Russo A, Tornello A, Maddalena L, Delios G, Marletto FP, De Micheli AG, Mattei A, Baldassano S, Canta F, Russo ML, Bergamo D, Vitale F, Liccardi MM, Chinaglia A, Calcagno A, Converso M, Aldieri C, Libanore V, Blangetti I, Benedetti V, Mitola B, Scozzari G; PLACO COVID Study Group. Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial. BMC Infect Dis. 2022 Nov 22;22(1):879. doi: 10.1186/s12879-022-07716-5.
PubMed 36418984
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04428021
- Acronym / sponsor ID
- PLACO-COVID / CS3/33
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- A.O.U. Città della Salute e della ScienzaUniversity, hospital or other
- Study start
- 15 Jun 2020 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Oct 2021 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
- Model description
- Three arms randomized trial, partially blinded
| Arm | Type | Receives |
|---|---|---|
| Standard therapy protocol (STP) | Active comparator | Drug: 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. |
| STP + Standard Plasma (SP) | Experimental | Drug: Standard Therapy Protocol (STP), Other: STP + Standard Plasma (SP)STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019) |
| STP + COVID-19 Convalescent Plasma (CP) | Experimental | Drug: Standard Therapy Protocol (STP), Other: 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- Pregnancy
- Previous severe reactions to plasma transfusion
- Unavailability of blood group compatible COVID-19 convalescent plasma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Therapy Protocol (STP)Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee | Drug | STP + COVID-19 Convalescent Plasma (CP), STP + Standard Plasma (SP), Standard therapy protocol (STP) |
| STP + Standard Plasma (SP)Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP | Other | STP + Standard Plasma (SP) |
| 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 | Other | STP + COVID-19 Convalescent Plasma (CP) |
Primary outcome
30-days survival
Time frame: 30 days after randomization
Proportion of patients alive 30 days after randomization
8 secondary outcomes
Ventilator free survival
Time frame: 30 days after randomization
6-months survival
Time frame: 6 months after randomization
Incidence of complications
Time frame: 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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2022.
- Derived from this study: PubMed 36418984Manzini PM, Ciccone G, De Rosa FG, Cavallo R, Ghisetti V, D'Antico S, Galassi C, Saccona F, Castiglione A, Birocco N, Francisci T, Hu H, Pecoraro C, Danielle F, Labanca L, Bordiga AM, Lorenzi M, Camisasca G, Giachino O, Pagliarino M, Ottone P, Scuvera ITD, Guaschino R, Freilone R, Berti P, Pittaluga F, Avolio M, Costa C, Raso S, Nucci A, Milan M, Baffa A, Russo A, Tornello A, Maddalena L, Delios G, Marletto FP, De Micheli AG, Mattei A, Baldassano S, Canta F, Russo ML, Bergamo D, Vitale F, Liccardi MM, Chinaglia A, Calcagno A, Converso M, Aldieri C, Libanore V, Blangetti I, Benedetti V, Mitola B, Scozzari G; PLACO COVID Study Group. Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial. BMC Infect Dis. 2022 Nov 22;22(1):879. doi: 10.1186/s12879-022-07716-5.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paola Maria Manzini, MD principal investigator
AO Città della salute e della scienza di Torino
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Standard Therapy Protocol (STP), STP + Standard Plasma (SP) and STP + COVID-19 Convalescent Plasma (CP) in people with COVID-19, run by A.O.U. Città della Salute e della Scienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
30-days survival (time frame: 30 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04428021, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2022.