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Convalescent Plasma as Treatment for Acute Coronavirus Disease (COVID-19)

Primary Purpose

COVID-19

Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
SARS-CoV-2 convalescent plasma
Sponsored by
Joakim Dillner
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID-19 convalescent plasma treatment, SARS-CoV-2 infection, Safety, Effectiveness

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Danderyd Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Convalescent plasma treatment

Arm Description

All participants will receive a bag of convalescent plasma. The bag volume will be 180-200 ml. The first 10 patients will receive 1, 5, 10, 50 and 134 ml of plasma at 30 minute intervals while being closely monitored for adverse events, especially allergic reactions. The remaining twenty patients will receive the convalescent plasma as a slow infusion according to normal routines.

Outcomes

Primary Outcome Measures

Disease progression
Decrease in progression to requiring non-invasive or invasive ventilation

Secondary Outcome Measures

Adverse events (AE)
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.
Time ro resolution of fever and symptoms
Measured daily until discharged from the hospital.
Clearance of viraemia
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)
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
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.
Inflammatory parameter haemoglobin (Hb)
Time to normalization of inflammatory parameter haemoglobin (Hb). Blood sample for this marker will be taken daily until normalized or discharged from hospital.
Inflammatory parameter Pro-calcitonin
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
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
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.

Full Information

First Posted
April 10, 2020
Last Updated
December 1, 2021
Sponsor
Joakim Dillner
Collaborators
Danderyd Hospital, Karolinska Institutet, Karolinska University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04390178
Brief Title
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

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
April 10, 2020 (Actual)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joakim Dillner
Collaborators
Danderyd Hospital, Karolinska Institutet, Karolinska University 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19 convalescent plasma treatment, SARS-CoV-2 infection, Safety, Effectiveness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
An open, non-randomised controlled, clinical trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Convalescent plasma treatment
Arm Type
Experimental
Arm Description
All participants will receive a bag of convalescent plasma. The bag volume will be 180-200 ml. The first 10 patients will receive 1, 5, 10, 50 and 134 ml of plasma at 30 minute intervals while being closely monitored for adverse events, especially allergic reactions. The remaining twenty patients will receive the convalescent plasma as a slow infusion according to normal routines.
Intervention Type
Biological
Intervention Name(s)
SARS-CoV-2 convalescent plasma
Intervention Description
Treatment with convalescent plasma (180-200ml) from individuals who have recovered from SARS-CoV-2 infection
Primary Outcome Measure Information:
Title
Disease progression
Description
Decrease in progression to requiring non-invasive or invasive ventilation
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Adverse events (AE)
Description
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.
Time Frame
The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion.
Title
Time ro resolution of fever and symptoms
Description
Measured daily until discharged from the hospital.
Time Frame
Until discharged from the hospital, up to 2 months
Title
Clearance of viraemia
Description
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.
Time Frame
Evaluated daily until discharge, at day 28, and last measurement taken at 6 months of follow-up after inclusion.
Title
Inflammatory parameter C-reactive protein (CRP)
Description
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.
Time Frame
Until discharged from the hospital, up to 2 months
Title
Inflammatory parameter white blood cell count
Description
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.
Time Frame
Until discharged from the hospital, up to 2 months
Title
Inflammatory parameter haemoglobin (Hb)
Description
Time to normalization of inflammatory parameter haemoglobin (Hb). Blood sample for this marker will be taken daily until normalized or discharged from hospital.
Time Frame
Until discharged from the hospital, up to 2 months
Title
Inflammatory parameter Pro-calcitonin
Description
Time to normalization of inflammatory parameter Pro-calcitonin. Blood sample for this marker will be taken daily until normalized or discharged from hospital.
Time Frame
Until discharged from the hospital, up to 2 months
Title
Inflammatory parameter Creatine Kinase
Description
Time to normalization of inflammatory parameter Creatine Kinase. Blood sample for this marker will be taken daily until normalized or discharged from hospital.
Time Frame
Until discharged from the hospital, up to 2 months
Title
Antibody response to SARS-CoV-2
Description
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.
Time Frame
Evaluated daily until discharge, at day 28, and last measurement taken at 6 months of follow-up after inclusion.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johan Ursing, MD, PhD
Organizational Affiliation
Danderyd Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Danderyd Hospital
City
Danderyd
ZIP/Postal Code
182 57
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
We will be sharing data but data the management plan is being designed.

Learn more about this trial

Convalescent Plasma as Treatment for Acute Coronavirus Disease (COVID-19)

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