Clinical trial NCT04649879: Convalescent Plasma for Treatment of COVID-19
Official title: Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: COVID-19 convalescent plasma treatment
SARS-CoV-2 infection
Viremia
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Danderyd Hospital
name: Falu Hospital
First posted: 2020-12-02
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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in which patients only received one dose of CP and a phase II study in which CP was given until viremia disappeared (unpublished data).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.


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

Primary outcomes:
measure: COVID-19 related mortality within 28 days
timeFrame: Measured 28 days after inclusion into the study.
Secondary outcomes:
measure: COVID-19 related mortality within 60 days
timeFrame: Measured 60 days after inclusion into the study.
measure: Requirement of invasive ventilation or Pao2/FiO2 ≤ 70 for ≥ 12 hours in the case of patients not eligible for intensive care
timeFrame: Until discharged from the hospital, up to 2 months
measure: Adverse events
timeFrame: The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion.
measure: Dose of plasma needed to clear viremia
timeFrame: 28 days
measure: Time to clearance of viremia
timeFrame: Until discharged from the hospital, up to 2 months
Other outcomes:
Locations:
city: Falun
country: Sweden
facility: Department of Infectious Disease, Falu Hospital
state: Dalarn
city: Stockholm
country: Sweden
facility: Department of Geriatrics, Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Danderyd Hospital
Study officials:
References:
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.