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

NCT04342182 | Terminated Phase 2 DMC

• 1 other identifier: NL73489.078.20
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 18

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

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Overall mortality until discharge from the hospital or a maximum of 60 days after admission whichever comes first

  the mortality in the 300ml convP group will be compared with the control arm

  until hospital discharge or a maximum of 60 days whichever comes first

Secondary Outcomes (12)

• Impact of 300ml convP therapy on hospital days

  until hospital discharge or a maximum of 60 days whichever comes first

• Impact of 300ml convP on weaning from oxygen therapy

  until hospital discharge or a maximum of 60 days whichever comes first

• Impact of 300ml convP on overall mortality in patients admitted to the ICU within 24 hours after admission

  until hospital discharge or a maximum of 60 days whichever comes first

• 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

  hospital discharge or a maximum of 60 days whichever comes first

• Impact of 300ml convP therapy on ICU days in patients admitted to the ICU within 24 hours after admission

  Until hospital discharge, estimated average 4 weeks

Study Arms (2)

Convalescent plasma

EXPERIMENTAL

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

Biological: Convalescent plasma

Standard of care

NO INTERVENTION

standard of care (supportive care, oxygen, antibiotics)

Interventions

Convalescent plasma 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

Convalescent plasma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Prothya Biosolutions: collaborator

Study Sites (18)

Erasmus Medical Center

Rotterdam, South Holland, 3000 CA, Netherlands

Location

NoordWest Ziekenhuisgroep

Alkmaar, Netherlands

Location

Onze Lieve Vrouwen Gasthuis

Amsterdam, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, Netherlands

Location

Martini Hospital

Groningen, Netherlands

Location

Spaarna Gasthuis

Haarlem, Netherlands

Location

Alrijne Ziekenhuis

Leiderdorp, Netherlands

Location

Sint Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Canisius-Wilhelmina Hospital

Nijmegen, Netherlands

Location

Maasstad Ziekenhuis

Rotterdam, Netherlands

Location

ZorgSaam Hospital

Terneuzen, Netherlands

Location

Haaglanden Medisch Centrum

The Hague, Netherlands

Location

Bernhoven Hospital

Uden, Netherlands

Location

VieCuri

Venlo, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 37162745 DERIVED

• 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.

  PMID: 36734509 DERIVED

• 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.

  PMID: 34013969 DERIVED

• 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.

  PMID: 33044747 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Bart Rijnders, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: This trial is a randomized comparative trial. Patients will be randomized between the infusion of 300mL of convP versus the standard of care.

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 10, 2020
• Study Start: April 8, 2020
• Primary Completion: July 1, 2020
• Study Completion: September 30, 2020
• Last Updated: April 1, 2022

Record last verified: 2022-03

Locations

NL (18)