COVID-19
Conditions
Keywords
COVID-19 convalescent plasma treatment, SARS-CoV-2 infection, Safety, Effectiveness
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.
Interventions
BIOLOGICALSARS-CoV-2 convalescent plasma
Treatment with convalescent plasma (180-200ml) from individuals who have recovered from SARS-CoV-2 infection
Sponsors
Danderyd Hospital
Karolinska Institutet
Karolinska University Hospital
Joakim Dillner
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
An open, non-randomised controlled, clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease progression | 28 days | Decrease in progression to requiring non-invasive or invasive ventilation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time ro resolution of fever and symptoms | Until discharged from the hospital, up to 2 months | Measured daily until discharged from the hospital. |
| Clearance of viraemia | Evaluated daily until discharge, at day 28, and last measurement taken at 6 months of follow-up after inclusion. | SARS-CoV-2 RNA detection by polymerase chain reaction (PCR) in blood or serum. Blood samples for immunological analyses and serology will be taken daily until discharge, on day 28, and at 6 months. |
| Inflammatory parameter C-reactive protein (CRP) | Until discharged from the hospital, up to 2 months | Time to normalization of inflammatory parameter C-reactive protein (CRP). Blood sample for this marker will be taken daily until normalized or discharged from hospital. |
| Inflammatory parameter white blood cell count | Until discharged from the hospital, up to 2 months | Time to normalization of inflammatory parameter white blood cell count (WBC). Blood sample for this marker will be taken daily until normalized or discharged from hospital. |
| Adverse events (AE) | The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion. | Adverse reactions and serious adverse reactions. The safety of the intervention will be assessed with regard to AEs, baseline medical conditions, and findings from the physical examination and laboratory tests. 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. |
| Inflammatory parameter Pro-calcitonin | Until discharged from the hospital, up to 2 months | Time to normalization of inflammatory parameter Pro-calcitonin. Blood sample for this marker will be taken daily until normalized or discharged from hospital. |
| Inflammatory parameter Creatine Kinase | Until discharged from the hospital, up to 2 months | Time to normalization of inflammatory parameter Creatine Kinase. Blood sample for this marker will be taken daily until normalized or discharged from hospital. |
| Antibody response to SARS-CoV-2 | Evaluated daily until discharge, at day 28, and last measurement taken at 6 months of follow-up after inclusion. | Change in the antibody response to SARS-CoV-2 as measured in serum. Blood samples for immunological analyses and serology will be taken daily until discharge, on day 28, and at 6 months. |
| Inflammatory parameter haemoglobin (Hb) | Until discharged from the hospital, up to 2 months | Time to normalization of inflammatory parameter haemoglobin (Hb). Blood sample for this marker will be taken daily until normalized or discharged from hospital. |
Countries
Sweden
Outcome results
None listed