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Convalescent Plasma as Therapy for Covid-19 Severe SARS-CoV-2 Disease (CONCOVID Study) (ConCoVid-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04342182
Recruitment Status : Active, not recruiting
First Posted : April 10, 2020
Last Update Posted : November 16, 2020
Sponsor:
Collaborator:
Sanquin Plasma Products BV
Information provided by (Responsible Party):
Bart Rijnders, Erasmus Medical Center

Tracking Information
First Submitted Date  ICMJE March 31, 2020
First Posted Date  ICMJE April 10, 2020
Last Update Posted Date November 16, 2020
Actual Study Start Date  ICMJE April 8, 2020
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
Overall mortality until discharge from the hospital or a maximum of 60 days after admission whichever comes first [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
the mortality in the 300ml convP group will be compared with the control arm
Original Primary Outcome Measures  ICMJE
 (submitted: April 9, 2020)
Overall mortality until discharge from the hospital or a maximum of 60 days after admission whichever comes first [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
the mortality in the 250ml convP group will be compared with the control arm
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2020)
  • Impact of 300ml convP therapy on hospital days [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
    the hospital days in the 300ml convP group will be compared with the control arm
  • Impact of 300ml convP on weaning from oxygen therapy [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
    A patient will be considered weaned from oxygen therapy when the patient did not receive oxygen for at least 24 hours.
  • Impact of 300ml convP on overall mortality in patients admitted to the ICU within 24 hours after admission [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
    the overall mortality in hospital days in patients admitted tot the ICU within 24 hours after admission in the 300ml convP group will be compared with the patients admitted tot the ICU within 24 hours after admission in the control arm
  • Difference in the effect of convP on mortality in patients with a duration of symptoms less or more the median duration of symptoms in the study population [ Time Frame: hospital discharge or a maximum of 60 days whichever comes first ]
    The mortality in patients with a duration of symptoms less than the median duration of symptoms in the study population will be compared with the mortality in patients with a duration of symptoms more than the median duration of symptoms in the study population
  • Impact of 300ml convP therapy on ICU days in patients admitted to the ICU within 24 hours after admission [ Time Frame: Until hospital discharge, estimated average 4 weeks ]
    the ICU days in hospital days in patients admitted to the ICU within 24 hours after admission in the 300ml convP group will be compared with the patients admitted tot the ICU within 24 hours after admission in the control arm
  • Impact of plasma therapy on the decrease in SARS-CoV2 shedding from airways [ Time Frame: until hospital discharge, estimated average 2 weeks ]
    airway samples will be taken on day 1 - 3 - 5 - 7 - 10 - 14 - and at discharge
  • Impact of CTL and NK cell immunity on the likelihood of being protected from immune serum transfer [ Time Frame: until hospital discharge, extimated average 2 weeks ]
    Blood wil be drawn at day 1, day 7 and day 14
  • Safety of convP therapy [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
    Evaluation of Severe Adverse Events and transfusion related adverse events
  • Change of the 8-point WHO COVID19 disease severity scale on day 15 [ Time Frame: until day 15 ]
    The WHO COVID19 disease severity scale on day 15 will be compared with the WHO COVID19 disease severity scale on day 1
  • Change of the 8-point WHO COVID19 disease severity scale on day 30 [ Time Frame: until day 30 ]
    The WHO COVID19 disease severity scale on day 30 will be compared with the WHO COVID19 disease severity scale on day 1 and day 15
  • Change of the 8-point WHO COVID19 disease severity scale on day 15 in the subgroup of patients with a baseline neutralizing antibody titer (PRNT50) <80. [ Time Frame: until day 15 ]
    The WHO COVID19 disease severity scale on day 15 will be compared with the WHO COVID19 disease severity scale on day 1 in patients with a baseline neutralizing antibody titer (PRNT50) <80.
  • Impact of plasma therapy on risk of long-term structural lung damage and lung function [ Time Frame: up to 12 months after plasma transfusion ]
    Low dose CT and lung function is done 6 weeks after discharge and if abnormal again 3 months after discharge.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2020)
  • Impact of 250ml convP therapy on hospital days [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
    the hospital days in the 250ml convP group will be compared with the control arm
  • Impact of 250ml convP on weaning from oxygen therapy [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
    A patient will be considered weaned from oxygen therapy when the patient did not receive oxygen for at least 24 hours.
  • Impact of 250ml convP on overall mortality in patients admitted to the ICU within 24 hours after admission [ Time Frame: until hospital discharge or a maximum of 60 days whichever comes first ]
    the overall mortality in hospital days in patients admitted tot the ICU within 24 hours after admission in the 250ml convP group will be compared with the patients admitted tot the ICU within 24 hours after admission in the control arm
  • Difference in the effect of convP on mortality in patients with a duration of symptoms less or more the median duration of symptoms in the study population [ Time Frame: hospital discharge or a maximum of 60 days whichever comes first ]
    The mortality in patients with a duration of symptoms less than the median duration of symptoms in the study population will be compared with the mortality in patients with a duration of symptoms more than the median duration of symptoms in the study population
  • Impact of 250ml convP therapy on ICU days in patients admitted to the ICU within 24 hours after admission [ Time Frame: Until hospital discharge, estimated average 4 weeks ]
    the ICU days in hospital days in patients admitted to the ICU within 24 hours after admission in the 250ml convP group will be compared with the patients admitted tot the ICU within 24 hours after admission in the control arm
  • Impact of plasma therapy on the decrease in SARS-CoV2 shedding from airways [ Time Frame: until hospital discharge, estimated average 2 weeks ]
    airway samples will be taken on day 1 - 3 - 5 - 7 - 10 - 14 - and at discharge
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Convalescent Plasma as Therapy for Covid-19 Severe SARS-CoV-2 Disease (CONCOVID Study)
Official Title  ICMJE Convalescent Plasma Therapy From Recovered Covid-19 Patients as Therapy for Hospitalized Patients With Covid-19
Brief Summary

Passive immunization with immunoglobulins is occasionally used as therapy for the treatment of viral infectious diseases. Immunoglobulins are used for the treatment of CMV disease, and is effective as prophylaxis when given soon after exposure to varicella zoster virus, rabies, and hepatitis B virus.

Neutralizing antibodies against MERS, SARS-CoV-1 and SARS-CoV-2 have been shown to be present in patients previously infected with MERS, SARS-CoV-1 and SARS-CoV-2 respectively. During the 2003 SARS outbreak in Hong-Kong,a non-randomized study in hospitalized SARS patients showed that treatment with convalescent plasma (convP) from SARS-recovered donors significantly increased the day 22 discharge rate and decreased mortality. A study in non-human primates showed that rhesus macaques could not be re-infected with SARS-CoV-2 after primary infection.

With no proven effective therapy against COVID, this study will evaluate the safety and efficacy of convalescent plasma from COVID-recovered donors as a treatment for hospitalized patients with symptomatic COVID-19. The study will focus on patients who tested positive for SARS-CoV-2 in the last 96 hours before inclusion

Primary objectives

• Decrease overall mortality in patients within COVID disease

Study design:

This trial is a randomized comparative trial. Patients will be randomized between the infusion of 300mL of convP with standard of care.

Patient population:

Patients with PCR confirmed COVID disease, age >18 years Donors will be included with a known history of COVID who have been asymptomatic for at least 14 days.

Intervention: 300mL of convP Duration of treatment: ConvP will be given as a one-time infusion Duration of follow up: For the primary endpoint: until discharge or death before day 60, whichever comes first. For the secondary endpoints (with separate consent) up to 1 year.

Target number of patients: 426 Target number of donors: 100 Expected duration of accrural: 36 months

Detailed Description

Secondary (exploratory) objectives

  • Evaluate the effect of 300ml convP on hospital stay
  • Evaluate the change of the 8-point WHO COVID19 disease severity scale on day 15 and 30
  • Evaluate the change of the 8-point WHO COVID19 disease severity scale on day 15 in the subgroup of patients with a baseline neutralizing antibody titer (PRNT50) <80
  • Evaluate the effect of 300ml convP on mortality in patients admitted to the ICU
  • Evaluate the effect of 300ml plasma therapy on hospital days for patients admitted to the ICU within 24 hours after admission
  • Evaluate the impact of plasma therapy on the decrease in SARS-CoV2 shedding from airways
  • Evaluate the difference in effect of convP on mortality in patients with a duration of symptoms < or > the median duration of symptoms in the study population
  • Evaluate the impact of CTL and NK cell immunity on the likelihood of being protected from immune serum transfer
  • Safety of convP therapy
  • Evaluate the impact of covP on long-term lung function
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This trial is a randomized comparative trial. Patients will be randomized between the infusion of 300mL of convP versus the standard of care.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE Biological: Convalescent plasma

Infusion of plasma retrieved from donors with a history of PCR proven symptomatic COVID.

Plasma will be administered according to the Erasmus MC KIS protocol regarding the use of blood products

Study Arms  ICMJE
  • Experimental: Convalescent plasma
    Standard of care plus 300mL of convalescent plasma from COVID-19 recovered donors
    Intervention: Biological: Convalescent plasma
  • No Intervention: Standard of care
    standard of care (supportive care, oxygen, antibiotics)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 9, 2020)
426
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2021
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with PCR confirmed COVID disease
  • Admitted to the hospital
  • The most recent PCR positive sample is <96hrs old
  • Written informed consent by patient or legal patient representative
  • Age at least 18 years

Exclusion Criteria:

  • Participation in another intervention trial on the treatment of COVID-19 that falls under the Dutch law human research (WMO) and in which individual patients are randomized to different treatment options
  • Known IgA deficiency
  • Invasive ventilation for already >96 hours

Donors: Eligibility for plasma donation

Inclusions Criteria:

  • A history of COVID infection that was documented by PCR
  • Known ABO-Resus(D) blood group
  • A screening for irregular antibodies with a titer ≤ 1:32
  • Asymptomatic for at least 14 days
  • Written informed consent regarding the plasmapheresis procedure
  • Tested negative for HIV, HBV, HCV, HEV, HTLV and syfilis

Exclusion Criteria:

  • Age <18 years and > 65 years
  • Weight <50kg
  • Medical history of heart failure
  • History of transfusion with red blood cells, platelets or plasma
  • History of organ- or tissue transplant
  • A cumulative stay in the United Kingdom of ≥ 6 months in the period between 01-01-1980 and 31-12-1996
  • A history of i.v. drug use
  • Insulin dependent diabetes
  • An underlying severe chronic illness (i.e. history of heart failure, cancer or stroke)
  • Tested positive for HLA- or HNA-antibodies
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04342182
Other Study ID Numbers  ICMJE NL73489.078.20
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bart Rijnders, Erasmus Medical Center
Study Sponsor  ICMJE Erasmus Medical Center
Collaborators  ICMJE Sanquin Plasma Products BV
Investigators  ICMJE
Principal Investigator: Bart Rijnders, MD, PhD Erasmus Medical Center
PRS Account Erasmus Medical Center
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP