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

NCT ID: NCT04342182

Last Updated: 2022-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-08

Study Completion Date

2020-09-30

Brief Summary

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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

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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

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This trial is a randomized comparative trial. Patients will be randomized between the infusion of 300mL of convP versus the standard of care.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Convalescent plasma

Standard of care plus 300mL of convalescent plasma from COVID-19 recovered donors

Group Type EXPERIMENTAL

Convalescent plasma

Intervention Type BIOLOGICAL

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

Standard of care

standard of care (supportive care, oxygen, antibiotics)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prothya Biosolutions

INDUSTRY

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Bart Rijnders

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bart Rijnders, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

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Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Site Status

NoordWest Ziekenhuisgroep

Alkmaar, , Netherlands

Site Status

Onze Lieve Vrouwen Gasthuis

Amsterdam, , Netherlands

Site Status

Rijnstate Ziekenhuis

Arnhem, , Netherlands

Site Status

Reinier de Graaf Gasthuis

Delft, , Netherlands

Site Status

Catharina Ziekenhuis

Eindhoven, , Netherlands

Site Status

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status

Groene Hart Ziekenhuis

Gouda, , Netherlands

Site Status

Martini Hospital

Groningen, , Netherlands

Site Status

Spaarna Gasthuis

Haarlem, , Netherlands

Site Status

Alrijne Ziekenhuis

Leiderdorp, , Netherlands

Site Status

Sint Antonius Ziekenhuis

Nieuwegein, , Netherlands

Site Status

Canisius-Wilhelmina Hospital

Nijmegen, , Netherlands

Site Status

Maasstad Ziekenhuis

Rotterdam, , Netherlands

Site Status

ZorgSaam Hospital

Terneuzen, , Netherlands

Site Status

Haaglanden Medisch Centrum

The Hague, , Netherlands

Site Status

Bernhoven Hospital

Uden, , Netherlands

Site Status

VieCuri

Venlo, , Netherlands

Site Status

Countries

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Netherlands

References

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Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 May 10;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub6.

Reference Type DERIVED
PMID: 37162745 (View on PubMed)

Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 Feb 1;2(2):CD013600. doi: 10.1002/14651858.CD013600.pub5.

Reference Type DERIVED
PMID: 36734509 (View on PubMed)

Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub4.

Reference Type DERIVED
PMID: 34013969 (View on PubMed)

Chai KL, Valk SJ, Piechotta V, Kimber C, Monsef I, Doree C, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2020 Oct 12;10:CD013600. doi: 10.1002/14651858.CD013600.pub3.

Reference Type DERIVED
PMID: 33044747 (View on PubMed)

Other Identifiers

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NL73489.078.20

Identifier Type: -

Identifier Source: org_study_id

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