Convalescent Plasma for Treatment of COVID-19
Primary Purpose
Covid19
Status
Completed
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
SARS-CoV-2 convalescent plasma
Standard of care
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring COVID-19 convalescent plasma treatment, SARS-CoV-2 infection, Viremia
Eligibility Criteria
Inclusion Criteria:
- Age greater than or equal to 18
- Admitted to a study hospital
- Active COVID-19 defined as symptoms + SARS CoV-2 identified from upper or lower airway samples and blood
- Negative pregnancy test taken before inclusion and use of an acceptable effective method of contraception until treatment discontinuation if the participant is a woman of childbearing potential
- Written informed consent after meeting with a study physician and ability and willingness to complete follow up
Exclusion Criteria:
- No matching plasma donor (Exact matching in the ABO system is required)
- Unavailability of plasma
- Estimated glomerular filtration rate <30 (kidney failure stage III or more)
- Pregnancy (urinary-hcg)
- Breast feeding
- Inability to give informed consent
Sites / Locations
- Department of Infectious Disease, Falu Hospital
- Department of Geriatrics, Karolinska University Hospital
- Danderyd Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Convalescent plasma treatment
Control
Arm Description
Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 10 CP infusions. If steroid therapy has not already been initiated, betamethasone 3 mg daily will be given concomitantly with steroid therapy or longer if clinically indicated but for a maximum of 10 days.
Standard of care for COVID-19 patients.
Outcomes
Primary Outcome Measures
COVID-19 related mortality within 28 days
Death of a study participant within 28 days.
Secondary Outcome Measures
COVID-19 related mortality within 60 days
Death of a study participant within 60 days.
Requirement of invasive ventilation or Pao2/FiO2 ≤ 70 for ≥ 12 hours in the case of patients not eligible for intensive care
The need for mechanical ventilation and date when this was initiated
For patients not eligible for intensive care: each day when PaO2/FiO2 ratio was less than 70 for ≥ 12 hours. PaO2 and FiO2 will be estimated from SO2% and O2 flow in nasal cannula, face mask or face mask with reservoir based on EPIC II data. A ratio of 70 is approximately equal to 90% SO2 with 8-9 L of Oxygen flow using a face mask with a reservoir.
Adverse events
Possible adverse events will be elicited using a modification and Swedish translation (appendix 6) of Common Terminology Criteria for Adverse Events v5.0 and they will be continuously reported to the sponsor. Adverse events related to convalescent plasma therapy shall be followed to assess reversibility.
Dose of plasma needed to clear viremia
Measured as doses of convalescent plasma administered (1-10 infusions, 200ml).
Time to clearance of viremia
Blood samples for detection of SARS-CoV-2 in the blood will be taken prior to treatment start, daily during treatment and until two consecutive negative results are obtained.
Full Information
NCT ID
NCT04649879
First Posted
December 1, 2020
Last Updated
January 26, 2022
Sponsor
Joakim Dillner
Collaborators
Karolinska Institutet, Danderyd Hospital, Falu Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04649879
Brief Title
Convalescent Plasma for Treatment of COVID-19
Official Title
Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
December 3, 2020 (Actual)
Primary Completion Date
January 26, 2022 (Actual)
Study Completion Date
January 26, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joakim Dillner
Collaborators
Karolinska Institutet, Danderyd Hospital, Falu Hospital
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
Convalescent plasma has been shown to be safe and effective for treatment of several diseases. Preliminary data indicate that it is safe for treatment of COVID-19. We found that viremia upon admission identifies patients at 7 fold increased risk of admission to intensive care and 8 fold increased risk of death. CP treatment appeared to result in rapid viral clearance in a small case series. CP appeared to be well tolerated in a phase I study in which patients only received one dose of CP and a phase II study in which CP was given until viremia disappeared (unpublished data).
Randomised controlled studies assessing the efficacy of CP are lacking and thus the efficacy of CP is unknown. Preliminary data indicate that treatment should be given early, prior to development of severe illness. Detection of viremia upon admission identifies a group at high risk of severe disease and death that has the most to benefit from CP. Phase II study data indicates that treatment should be given until SARS-CoV-2 is no longer detected in serum and the donor antibody neutralization titres should be ≥1/640. A randomised controlled trial in which viremic patients are treated with CP with the equivalent of an antibody titre ≥1/640 is thus required to determine if CP can be an effective COVID-19 treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
COVID-19 convalescent plasma treatment, SARS-CoV-2 infection, Viremia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomised 2:1 to treatment with convalescent plasma and standard of care only. Randomisation is by random permutated blocks using Redcap or equivalent.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Convalescent plasma treatment
Arm Type
Experimental
Arm Description
Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 10 CP infusions.
If steroid therapy has not already been initiated, betamethasone 3 mg daily will be given concomitantly with steroid therapy or longer if clinically indicated but for a maximum of 10 days.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Standard of care for COVID-19 patients.
Intervention Type
Biological
Intervention Name(s)
SARS-CoV-2 convalescent plasma
Intervention Description
Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 10 CP infusions. CP will be given as a slow infusion over 2 hours. CP neutralization titre of ≥ 1/640 or an ELISA reactivity against the Spike protein of SARS-CoV-2 by the Euroimmun commercial assay >9 is desired. New antibody tests are under development and can be used instead if equivalence to neutralization or Euroimmun ELISA is demonstrated.
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
Standard of care as determined by hospital practices for COVID-19 patients.
Primary Outcome Measure Information:
Title
COVID-19 related mortality within 28 days
Description
Death of a study participant within 28 days.
Time Frame
Measured 28 days after inclusion into the study.
Secondary Outcome Measure Information:
Title
COVID-19 related mortality within 60 days
Description
Death of a study participant within 60 days.
Time Frame
Measured 60 days after inclusion into the study.
Title
Requirement of invasive ventilation or Pao2/FiO2 ≤ 70 for ≥ 12 hours in the case of patients not eligible for intensive care
Description
The need for mechanical ventilation and date when this was initiated
For patients not eligible for intensive care: each day when PaO2/FiO2 ratio was less than 70 for ≥ 12 hours. PaO2 and FiO2 will be estimated from SO2% and O2 flow in nasal cannula, face mask or face mask with reservoir based on EPIC II data. A ratio of 70 is approximately equal to 90% SO2 with 8-9 L of Oxygen flow using a face mask with a reservoir.
Time Frame
Until discharged from the hospital, up to 2 months
Title
Adverse events
Description
Possible adverse events will be elicited using a modification and Swedish translation (appendix 6) of Common Terminology Criteria for Adverse Events v5.0 and they will be continuously reported to the sponsor. Adverse events related to convalescent plasma therapy shall be followed to assess reversibility.
Time Frame
The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion.
Title
Dose of plasma needed to clear viremia
Description
Measured as doses of convalescent plasma administered (1-10 infusions, 200ml).
Time Frame
28 days
Title
Time to clearance of viremia
Description
Blood samples for detection of SARS-CoV-2 in the blood will be taken prior to treatment start, daily during treatment and until two consecutive negative results are obtained.
Time Frame
Until discharged from the hospital, up to 2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age greater than or equal to 18
Admitted to a study hospital
Active COVID-19 defined as symptoms + SARS CoV-2 identified from upper or lower airway samples and blood
Negative pregnancy test taken before inclusion and use of an acceptable effective method of contraception until treatment discontinuation if the participant is a woman of childbearing potential
Written informed consent after meeting with a study physician and ability and willingness to complete follow up
Exclusion Criteria:
No matching plasma donor (Exact matching in the ABO system is required)
Unavailability of plasma
Estimated glomerular filtration rate <30 (kidney failure stage III or more)
Pregnancy (urinary-hcg)
Breast feeding
Inability to give informed consent
Facility Information:
Facility Name
Department of Infectious Disease, Falu Hospital
City
Falun
State/Province
Dalarn
ZIP/Postal Code
79182
Country
Sweden
Facility Name
Department of Geriatrics, Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
Facility Name
Danderyd Hospital
City
Stockholm
ZIP/Postal Code
18257
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The investigators will be sharing the data, but the management plan is being designed.
Citations:
PubMed Identifier
34880010
Citation
Dillner J, Ursing J. Convalescent plasma for treatment of COVID-19: study protocol for an open randomised controlled trial in Sweden. BMJ Open. 2021 Dec 8;11(12):e048337. doi: 10.1136/bmjopen-2020-048337.
Results Reference
derived
Learn more about this trial
Convalescent Plasma for Treatment of COVID-19
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