Clinical trial NCT04390178: Convalescent Plasma as Treatment for Acute Coronavirus Disease (COVID-19)
Official title: Plasma From Individuals Who Have Recovered From Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection as Treatment for Acute COVID-19 Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Keywords: COVID-19 convalescent plasma treatment
SARS-CoV-2 infection
Safety
Effectiveness
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Danderyd Hospital
name: Karolinska Institutet
name: Karolinska University Hospital
First posted: 2020-05-15
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: An open, non-randomised controlled, clinical trial
Primary purpose: TREATMENT

Brief summary: There is currently no effective treatment for COVID-19 except best supportive care. The aim is assess the safety, tolerability and efficacy of convalescent plasma for treatment of patients with varying degrees of COVID-19 illness.

Detailed description: 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-19. However, data is limited to small studies and case series on severely ill patients. The proposed study assesses the safety and efficacy earlier in the course of illness, in slightly less severe patients with the possibility of detecting less severe adverse events and the potential for early treatment to hinder the development of severe disease. Plasma is collected from consenting donors who have recovered from SARS-CoV-2.

Eligibility criteria: Inclusion Criteria:

* Age 18 and \<81 years
* Active COVID-19 defined as symptoms + SARS CoV-2 identified from upper or lower airway samples
* Fever ≥38.5C, admitted to a study hospital, hypoxemia defined as having a peripheral oxygen saturation below 93% (measured by pulse oximetry) and a breathing rate of \>20 breaths per minute without supplemental oxygen treatment
* A 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 and the Rh system is required)
* Unavailability of plasma
* Significant growth of alternative lower airway pathogen such as Streptococcus pneumoniae or Haemophilus influenzae in sputum
* Disease duration \>8 Days
* Estimated glomerular filtration rate \<60 (kidney failure stage III or more)
* Pregnancy (urinary-hcg), breast feeding,
* History of severe allergic reactions
* Inability to give informed consent
* Significantly compromised immunity.\*

  * Compromised immunity includes but is not limited to treatment with major immunosuppressive agents including high dose corticosteroids, anti-tumor necrosis factor (TNF) agents, calcineurin inhibitors, mTOR inhibitors, lymphocyte depleting biological agents, chemotherapeutic anti neoplastic agents. Also patients with advanced HIV/AIDS, severe immunodeficiency such as hypoglobulinemia, decompensated liver cirrhosis and bone marrow transplant the last year will be excluded.

Primary outcomes:
measure: Disease progression
timeFrame: 28 days
Secondary outcomes:
measure: Adverse events (AE)
timeFrame: The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion.
measure: Time ro resolution of fever and symptoms
timeFrame: Until discharged from the hospital, up to 2 months
measure: Clearance of viraemia
timeFrame: Evaluated daily until discharge, at day 28, and last measurement taken at 6 months of follow-up after inclusion.
measure: Inflammatory parameter C-reactive protein (CRP)
timeFrame: Until discharged from the hospital, up to 2 months
measure: Inflammatory parameter white blood cell count
timeFrame: Until discharged from the hospital, up to 2 months
measure: Inflammatory parameter haemoglobin (Hb)
timeFrame: Until discharged from the hospital, up to 2 months
measure: Inflammatory parameter Pro-calcitonin
timeFrame: Until discharged from the hospital, up to 2 months
measure: Inflammatory parameter Creatine Kinase
timeFrame: Until discharged from the hospital, up to 2 months
measure: Antibody response to SARS-CoV-2
timeFrame: Evaluated daily until discharge, at day 28, and last measurement taken at 6 months of follow-up after inclusion.
Other outcomes:
Locations:
city: Danderyd
country: Sweden
facility: Danderyd Hospital
Study officials:
affiliation: Danderyd Hospital
name: Johan Ursing, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: