Clinical trial NCT04384497: Convalescent Plasma for Treatment of COVID-19: An Exploratory Dose Identifying Study
Official title: Convalescent Plasma for Treatment of COVID-19: An Exploratory Dose Identifying Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Keywords: COVID-19 convalescent plasma treatment
SARS-CoV-2 infection
Dosing
Safety
Effectiveness
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Danderyd Hospital
name: Karolinska University Hospital
name: Karolinska Institutet
First posted: 2020-05-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: An open, non-randomised controlled, safety and dose identifying clinical trial
Primary purpose: TREATMENT

Brief summary: Convalescent plasma has been shown to be safe and effective for treatment of several diseases. Preliminary data indicates that it is safe and effective for treatment of COVID. However, data is limited to small studies and case series on severely ill patients.

In a preliminary safety study 10 patients with severe COVID-19, defined as requiring supplementary oxygen, having fever and a duration of illness less than 11 days were treated with 200 ml of CP. CP was given as a slow infusion without obvious adverse events. Eight patients had viremia. One patient rapidly cleared the virus and recovered following CP treatment. CP infusion did not appear to clear viremia in 7/8 patients. Five of these were eventually admitted to ICU. Thus CP did not appear to cause acute toxicity but did not seem to be effective at the dose used. Viremia seemed to be a marker of a high risk of disease progression The proposed study thus aims to treat a high risk population identified by having viremia irrespective of but hopefully before they develop pulmonary injury such that they require supplementary oxygen therapy. Moreover the dose of plasma will be increased incrementally with the aim of clearing viremia as our initial study indicates that continued viremia is driving COVID-19.


Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* Admitted to a study hospital
* Active COVID-19 defined as symptoms + SARS CoV-2 identified from upper or lower airway samples
* 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 both the ABO system is required)
* Unavailability of plasma
* Significant growth of alternative lower airway pathogen such as Streptococcus pneumoniae or Haemophilus influenzae in sputum
* Estimated glomerular filtration rate \<60 (kidney failure stage III or more)
* Pregnancy (urinary-hcg)
* Breast feeding
* History of severe allergic reactions to foods or other substances that the donor may have been exposed to (for example severe peanut allergy)
* Inability to give informed consent

Primary outcomes:
measure: Number and proportion of patients with progression to ventilation or sustained requirement of supplementary oxygen therapy
timeFrame: Measured in the first 28 days after inclusion.
Secondary outcomes:
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: Clearance of viremia
timeFrame: 6 months.
measure: Fever and symptoms
timeFrame: Until discharged from the hospital, up to 2 months
measure: Inflammatory parameters
timeFrame: Until discharged from the hospital, up to 2 months
measure: Antibody response to SARS-CoV-2
timeFrame: 6 months
Other outcomes:
Locations:
city: Danderyd
country: Sweden
facility: Danderyd Hospital
state: Stockholm
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Danderyd Hospital
name: Johan Ursing, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: