Covid19Phase 2CP_COVID-19NCT04730401
Convalescent Plasma in the Treatment of Covid-19
A Phase 2 study testing Convalescent plasma from COVID-19 donors in people with Covid19, run by Helsinki University Central Hospital at 1 site in Finland.
Trial summary
This study investigates the possible adverse effects and effectiveness of convalescent plasma for patients infected with SARS-CoV-2. Following provision of informed consent, patients will be randomized into three groups: High-titre convalescent plasma, low-titre convalescent plasma or placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Convalescent plasma from COVID-19 donors
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 390 participants
- Where
- 1 siteFinland
- Study dates
- 27 Jan 2021to 30 Jan 2023
- 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
- Acute Covid-19 disease at the time of recruitment laboratory-confirmed by upper respiratory tract PCR
- Patient recently (0-4 days earlier) admitted to hospital due to Covid-19 infection
- Symptom onset 10 days before recruitment (if symptom onset unknown the duration is calculated from positive PCR-test)
- the day should be recorded from the duration of the Covid-19 symptoms/positive test result
- The dose of LMWH thromboprofylaxis should be recorded
- Written informed consent.
Who cannot join
- Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of IMP; oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent are excluded ( inhaled or topical steroids allowed)
- Regular (daily), systemic administration of corticosteroids at the time on inclusion (inhaled or topical corticosteroids are allowed)
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
- Pregnancy or lactation.
- Alcohol or drug abuse.
- Suspected non-compliance.
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- Presence of VTE, including pulmonary embolism or other manifestations of thrombosis
- Use of any investigational drug (other than hydroxychloroquine) or vaccine within 30 days prior to first dose of study vaccine or planned use during study period.
- Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction as judged by investigator.
- Known immunoglobulin A (IgA) deficiency
- Existing treatment limitations: do-not-resuscitate (DNR) order or withholding treatment in ICU
- Any other criteria which, as judged by investigator, might compromise a patient's well-being or ability to participate in the study or its outcome.
- Active malignant disease
- CP not available for patients blood type
- Patient cannot assign written consent
- No personnel available for CP of placebo transfusion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Double-Blind, Placebo-Controlled Study of Convalescent Plasma in the Treatment of Covid-19
This study investigates the possible adverse effects and effectiveness of convalescent plasma for patients infected with SARS-CoV-2. Following provision of informed consent, patients will be randomized into three groups: High-titre convalescent plasma, low-titre convalescent plasma or placebo. Primary outcomes of the study will cover safety and either intubation or initiation of systemic corticosteroids. Safety information collected will include serious adverse events judged to be related to administration of convalescent plasma. Microbiological and other laboratory parameters will be followed up.
Read the detailed description
SARS-CoV-2 pandemic presents a serious global public health threat urgently requiring both prophylactic and therapeutic interventions. The entry of SARS-CoV-2 into human cells involves a binding between its spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) receptor on human cells. Convalescent sera of Covid-19 patients have been shown to contain SARS-CoV-2-neutralizing antibodies. Accordingly, recovered patients are presumed to be immune to re-infection. Use of convalescent plasma as treatment warrants research, which is supported by the European Commission. Convalescent plasma (CP) therapy is a classical adaptive immunotherapy. It has been applied to prevention and treatment of various infectious diseases: evidence of success has been accumulated e.g. on treatment of SARS, MERS, and 2009 H1N1, for which satisfactory efficacy and safety have been shown.
The investigators will select as donors for CP therapy patients recovered from Covid-19 with a high neutralizing antibody titre who meet normal blood donor eligibility criteria. The donors will be recruited among participants of ongoing Covid-19 immunity studies (Clin-Covid, Commun-Covid) and/or from Finnish Red Cross Blood Service (FRCBS) blood donors.
CP will be prepared from the blood of eligible donors at the FRCBS according to previous protocols and the European guidelines for fresh frozen plasma. After the screening test results required for product release (HCV, HBV, HIV, ABO, Syphilis) are available, the units will be released. All donors will be screened for type-I-Interferon antibodies and women will be screened for HLA-antibodies. The units will be labelled with convalescence plasma labels including ICCBBA/ISBT compliant product codes. The plasma units will be frozen to -25°C within 6 hours from collection. Prior to freezing 3 ml of CP will be separated and divided in 3 aliquots to be stored, for possible later analysis.
Patients admitted to ward at HUH will be randomized 1:1:1 into three groups which will be given 1) high-titre convalescent plasma (HCP), 2) low-titre convalescent plasma (LCP) or 3) placebo. The plasma preparations and placebo will be given as one 200 mL infusion. ABORh blood group will be determined from patients prior to transfusion according to normal transfusion protocols of the hospital. The study will be double-blinded with saline as placebo given to groups three. The primary outcomes of the study will cover safety and intubation/initiation of systemic corticosteroids. AEs will be reviewed, recorded and reported up to 6 hours after administration of CP or placebo. Thromboembolic and cardiovascular events will be recorded as AEs or SAEs up to 7 days after administration of CP / placebo. SAEs will be reviewed, recorded and reported up to 7 days after administration of CP / placebo. In case of respiratory failures classified as SAEs, the reporting period is only up to 12 hours after administration of CP / placebo.
- Conditions
- Covid19
- Being tested
- Convalescent plasma from COVID-19 donors, Placebo
- Keywords
- Covid-19, Convalescent plasma, Safety
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Convalescent plasma from COVID-19 donorsBiological
Convalescent plasma from COVID-19 donors
PlaceboBiological
200mL saline
| Study group | Role | What they receive |
|---|---|---|
| High-titre CP | Experimental | 200mL high-titre CP on admittance Receives: Biological: Convalescent plasma from COVID-19 donors |
| low-titre CP | Active comparator | 200ml low-titre CP on admittance Receives: Biological: Convalescent plasma from COVID-19 donors |
| Placebo | Placebo comparator | 200mL saline as placebo on admittance Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (SAE)
Immediate serious adverse events (SAE) between active and non-active group
Measured: SAEs will be reviewed, recorded and reported up to 6 hours after administration of CP or placebo.
Safety (SAE)
Subsequent serious adverse events (SAE) between active and non-active group
Measured: SAEs will be recorded and reported up to 7 days after administration of CP or placebo.
Rate of intubation or systemic corticosteroids initiation
Intubation or systemic corticosteroid treatment (e.g. dexamethasone) started for aggravation of Covid-19
Measured: 21 days post transfusion
Secondary outcomes (15)
Hospital stay
Number of days at hospital during the COVID-19 infection hospital period
Measured: Through study completion, up to 1 year
Mortality
Proportion of fatal cases during the COVID-19 infection hospital period
Measured: Through study completion, up to 1 year
Mortality
Proportion of fatal cases during the COVID-19 infection hospital period
Measured: 21 days post transfusion
ICU stay
Number of ICU days during the COVID-19 infection hospital period
Measured: Within 21 days post transfusion
Ventilator days
Number of ventilator days during the COVID-19 infection hospital period
Measured: Within 21 days post transfusion
Severity of respiratory failure
Highest severity of respiratory failure using adapted WHO Clinical Progression Scale
Measured: 21 days post transfusion
Viral load
Analyses of respiratory tract secretions by SARS-CoV-2 PCR during the COVID-19 infection hospital period
Measured: During hospitalizaation, through study completion, up to 1 year
Antibody measurements
Analyses of SARS-CoV-2-specific antibodies in serum and excretions
Measured: Through study completion, up to 1 year
Thrombotic complication
Development of a thrombotic complication, including VTE or arterial thrombosis
Measured: Through study completion, up to 1 year
The rate of participants presenting with coagulopathy disorders
Development of sepsis-induced coagulopathy or disseminated intravascular coagulation during the COVID-19 infection hospital period
Measured: 21 days post transfusion
Number of participants with laboratory change
Change in inflammatory (CRP, Ferritin) and coagulopathy (P -APTT, P -AT3, P -Fibr, P -FiDD, P -FVIII., P -Trombai ja P -TT) markers during the COVID-19 infection hospital period
Measured: Through study completion, up to 1 year
Adverse effects
Comparison of adverse events between active and non-active group
Measured: Through study completion, up to 1 year
Convalescent plasma efficacy
Convalescent plasma (high or low titer) efficacy versus placebo: rate of intubation or initiating systemic corticosteroids during the COVID-19 infection hospital period
Measured: 21 day post transfusion
Convalescent plasma high vs low titer efficacy
Comparison of efficacy of high titer CP to low titer CP: Rate of intubation or initiating systemic corticosteroids during the COVID-19 infection hospital period
Measured: 21 day post transfusion
Convalescent plasma efficacy according to donor status
Comparison of efficacy CP obtained from vaccinated donors versus non-vaccinated donors: Rate of intubation or initiating systemic corticosteroids during the COVID-19 infection hospital period
Measured: 21 day post transfusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start27 Jan 2021
- Primary completion30 Jan 2022
- Study completion30 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- 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
- Double blind, randomized, placebo controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 390 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Finnish Red Cross Blood Service
- Responsible party
- Principal investigator, Anu Kantele, Helsinki University Central Hospital
- Investigators
- Anu Kantele, MD,Prof, Principal investigator, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04730401
- Sponsor's protocol ID
- Plasma_Covid-19
- Acronym
- CP_COVID-19
- Status last verified
- Jul 2022
- First submitted
- 26 Jan 2021
- Last updated
- 7 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Blind, Placebo-Controlled Study of Convalescent Plasma in the Treatment of Covid-19
- ClinicalTrials.gov ID
- NCT04730401
- Acronym / sponsor ID
- CP_COVID-19 / Plasma_Covid-19
- Conditions
- Covid19
- Keywords
- Covid-19, Convalescent plasma, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 390 participants (estimated)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- Finnish Red Cross Blood Service
- Study start
- 27 Jan 2021 (actual)
- Primary completion
- 30 Jan 2022 (actual)
- Study completion
- 30 Jan 2023 (estimated)
- First posted
- 29 Jan 2021 (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.
This study investigates the possible adverse effects and effectiveness of convalescent plasma for patients infected with SARS-CoV-2. Following provision of informed consent, patients will be randomized into three groups: High-titre convalescent plasma, low-titre convalescent plasma or placebo. Primary outcomes of the study will cover safety and either intubation or initiation of systemic corticosteroids. Safety information collected will include serious adverse events judged to be related to administration of convalescent plasma. Microbiological and other laboratory parameters will be followed up.
Detailed description
SARS-CoV-2 pandemic presents a serious global public health threat urgently requiring both prophylactic and therapeutic interventions. The entry of SARS-CoV-2 into human cells involves a binding between its spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) receptor on human cells. Convalescent sera of Covid-19 patients have been shown to contain SARS-CoV-2-neutralizing antibodies. Accordingly, recovered patients are presumed to be immune to re-infection. Use of convalescent plasma as treatment warrants research, which is supported by the European Commission. Convalescent plasma (CP) therapy is a classical adaptive immunotherapy. It has been applied to prevention and treatment of various infectious diseases: evidence of success has been accumulated e.g. on treatment of SARS, MERS, and 2009 H1N1, for which satisfactory efficacy and safety have been shown.
The investigators will select as donors for CP therapy patients recovered from Covid-19 with a high neutralizing antibody titre who meet normal blood donor eligibility criteria. The donors will be recruited among participants of ongoing Covid-19 immunity studies (Clin-Covid, Commun-Covid) and/or from Finnish Red Cross Blood Service (FRCBS) blood donors.
CP will be prepared from the blood of eligible donors at the FRCBS according to previous protocols and the European guidelines for fresh frozen plasma. After the screening test results required for product release (HCV, HBV, HIV, ABO, Syphilis) are available, the units will be released. All donors will be screened for type-I-Interferon antibodies and women will be screened for HLA-antibodies. The units will be labelled with convalescence plasma labels including ICCBBA/ISBT compliant product codes. The plasma units will be frozen to -25°C within 6 hours from collection. Prior to freezing 3 ml of CP will be separated and divided in 3 aliquots to be stored, for possible later analysis.
Patients admitted to ward at HUH will be randomized 1:1:1 into three groups which will be given 1) high-titre convalescent plasma (HCP), 2) low-titre convalescent plasma (LCP) or 3) placebo. The plasma preparations and placebo will be given as one 200 mL infusion. ABORh blood group will be determined from patients prior to transfusion according to normal transfusion protocols of the hospital. The study will be double-blinded with saline as placebo given to groups three. The primary outcomes of the study will cover safety and intubation/initiation of systemic corticosteroids. AEs will be reviewed, recorded and reported up to 6 hours after administration of CP or placebo. Thromboembolic and cardiovascular events will be recorded as AEs or SAEs up to 7 days after administration of CP / placebo. SAEs will be reviewed, recorded and reported up to 7 days after administration of CP / placebo. In case of respiratory failures classified as SAEs, the reporting period is only up to 12 hours after administration of CP / placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Double blind, randomized, placebo controlled trial
| Arm | Type | Receives |
|---|---|---|
| High-titre CP | Experimental | Biological: Convalescent plasma from COVID-19 donors200mL high-titre CP on admittance |
| low-titre CP | Active comparator | Biological: Convalescent plasma from COVID-19 donors200ml low-titre CP on admittance |
| Placebo | Placebo comparator | Biological: Placebo200mL saline as placebo on admittance |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Acute Covid-19 disease at the time of recruitment laboratory-confirmed by upper respiratory tract PCR
- Patient recently (0-4 days earlier) admitted to hospital due to Covid-19 infection
- Symptom onset 10 days before recruitment (if symptom onset unknown the duration is calculated from positive PCR-test)
- the day should be recorded from the duration of the Covid-19 symptoms/positive test result
- The dose of LMWH thromboprofylaxis should be recorded
Key exclusion criteria (16 listed)
- Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of IMP; oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent are excluded ( inhaled or topical steroids allowed)
- Regular (daily), systemic administration of corticosteroids at the time on inclusion (inhaled or topical corticosteroids are allowed)
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
- Pregnancy or lactation.
- Alcohol or drug abuse.
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 |
|---|---|---|
| Convalescent plasma from COVID-19 donorsConvalescent plasma from COVID-19 donors | Biological | High-titre CP, low-titre CP |
| Placebo200mL saline | Biological | Placebo |
Primary outcome
Safety (SAE)
Time frame: SAEs will be reviewed, recorded and reported up to 6 hours after administration of CP or placebo.
Immediate serious adverse events (SAE) between active and non-active group
Safety (SAE)
Time frame: SAEs will be recorded and reported up to 7 days after administration of CP or placebo.
Subsequent serious adverse events (SAE) between active and non-active group
Rate of intubation or systemic corticosteroids initiation
Time frame: 21 days post transfusion
Intubation or systemic corticosteroid treatment (e.g. dexamethasone) started for aggravation of Covid-19
15 secondary outcomes
Hospital stay
Time frame: Through study completion, up to 1 year
Mortality
Time frame: Through study completion, up to 1 year
Mortality
Time frame: 21 days post transfusion
ICU stay
Time frame: Within 21 days post transfusion
Ventilator days
Time frame: Within 21 days post transfusion
Severity of respiratory failure
Time frame: 21 days post transfusion
Viral load
Time frame: During hospitalizaation, through study completion, up to 1 year
Antibody measurements
Time frame: Through study completion, up to 1 year
Thrombotic complication
Time frame: Through study completion, up to 1 year
The rate of participants presenting with coagulopathy disorders
Time frame: 21 days post transfusion
Number of participants with laboratory change
Time frame: Through study completion, up to 1 year
Adverse effects
Time frame: Through study completion, up to 1 year
Convalescent plasma efficacy
Time frame: 21 day post transfusion
Convalescent plasma high vs low titer efficacy
Time frame: 21 day post transfusion
Convalescent plasma efficacy according to donor status
Time frame: 21 day post transfusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2022.
- Individual participant dataSharing planned: No
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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.
Anu Kantele, MD,Prof principal investigator
Helsinki University Central Hospital
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 Convalescent plasma from COVID-19 donors in people with Covid19, run by Helsinki University Central Hospital at 1 site in Finland.
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 6 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 7 Jul 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 Finland. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
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?
Safety (SAE) (time frame: SAEs will be reviewed, recorded and reported up to 6 hours after administration of CP or placebo.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jul 2022.