Covid19Phase 3CoV-EarlyNCT04589949
Early Convalescent Plasma Therapy for High-risk Patients With COVID-19 in Primary Care (the CoV-Early Study)
A Phase 3 study testing ConvP and FFP in people with Covid19, run by Erasmus Medical Center at 11 sites in Netherlands.
Trial summary
An effective, widely available, and safe treatment that can decrease the duration, severity and fatality of COVID-19 is urgently needed. Also, in the most affected regions the pressure on health care systems including ventilator support capacity can be a limiting factor for survival. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- ConvP and FFP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 420 participants
- Where
- 11 sitesNetherlands
- Study dates
- 12 Oct 2020to 1 Mar 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- RT-PCR-confirmed COVID-19.
- Symptomatic (e.g but not limited to fatigue, fever, cough, dyspnoea, loss of taste or smell, diarrhea, falls or confusion)
- 70 years or older OR 50-69 years and 1 or more of the risk factors described in the protocol
Who cannot join
- Life expectancy <28 days in the opinion of the treating physician
- Patient or legal representative is unable to provide written informed consent
- Symptomatic for 8 days or more
- Being admitted to the hospital at the informed consent procedure
- Known previous history of transfusion-related acute lung injury
- Known Immunoglobulin A (IgA) deficiency
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Netherlands11 sites
Meander Medisch Centrum
Amersfoort
Rijnstate Ziekenhuis
Arnhem
Amphia Ziekenhuis
Breda
Groene Hart Ziekenhuis
Gouda
University Medical Center Groningen (UMCG)
Groningen
Spaarne Gasthuis
Haarlem
Medisch Centrum Leeuwarden
Leeuwarden
Leids Universitair Medisch Centrum
Leiden
Sint Antonius Ziekenhuis
Nieuwegein
Erasmus Medical Center
Rotterdam, South Holland, 3000 CA
Bernhoven Hospital
Uden
About this study
An effective, widely available, and safe treatment that can decrease the duration, severity and fatality of COVID-19 is urgently needed. Also, in the most affected regions the pressure on health care systems including ventilator support capacity can be a limiting factor for survival. Initial studies including from our group indicate that administering convalescent plasma containing high titers of neutralizing antibodies to COVID-19 patients who are already relatively late during the disease course after hospital admission is not effective, which can be explained by high titers of autologous antibodies present in patients. Thus, the antiviral capacity of convalescent plasma is hypothesized to be best positioned early in the disease course and in patients at increased risk for a severe disease course. If effective, any treatment that decreases the need for hospital admission is very valuable but so far, no COVID-19 treatment has been shown to prevent clinical deterioration when given before patients are admitted to the hospital.
Primary objective:
Read more
To evaluate the efficacy, feasibility and safety following the administration of convalescent plasma (ConvP) as a therapy for outpatients diagnosed with COVID-19 at increased risk for an unfavourable clinical outcome and within 7 days after symptom onset.
Study design:
This trial is a nationwide multicenter, double blind, randomized controlled trial in the Netherlands. Patients will be randomized between the transfusion of 300mL of convP versus regular fresh frozen plasma (FFP).
Patient population:
Patients with polymerase chain reaction (PCR) confirmed COVID disease with less than 8 days of symptoms, age 70 or older or 50-69 years with at least 1 additional risk factor for severe COVID-19 are eligible.
Intervention:
300mL of convP with a minimum level of neutralizing antibodies.
A total of 690 patients will be included. Expected duration of accrual: 18-24 months Duration of follow up :Day 28 for the primary endpoint
Read the detailed description
Secondary (exploratory) objectives
- To evaluate the impact of 300mL convP on mortality
- To evaluate the impact of 300mL convP on hospital admission
- To evaluate the impact of 300mL convP on admission to ICU
- To evaluate the impact of 300mL convP on duration of symptoms
- To evaluate the impact of 300mL convP in relation to the age and clinical frailty of the patient
- Conditions
- Covid19
- Being tested
- ConvP, FFP
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ConvPBiological
Also called 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
FFPBiological
Also called Fresh Frozen Plasma
Infusion of thawed non-convalescent plasma Plasma will be administered according to the Erasmus Medical Center quality protocol regarding the use of blood products
| Study group | Role | What they receive |
|---|---|---|
| ConvP | Experimental | 300 mL convalescent plasma with a minimum of neutralizing antibodies Receives: Biological: ConvP |
| FFP | Active comparator | 300 mL Fresh Frozen plasma Receives: Biological: FFP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Highest disease status
Highest disease status on the 5-point ordinal disease severity scale in the convP group will be compared with the FFP group.
Measured: 28 days following transfusion of convP or FFP
Secondary outcomes (5)
Percentage of deaths
Percentage of deaths in the convP group compared to the FFP group
Measured: 28 days following transfusion of convP or FFP
Percentage of hospital admissions
Percentage of hospital admissions in the convP group compared to the FFP group
Measured: 28 days following transfusion of convP or FFP
Percentage of ICU admissions
Percentage of ICU admissions in the convP group compared to the FFP group
Measured: 28 days following transfusion of convP or FFP
Disease duration in days of symptoms
Disease duration in days of symptoms in the convP group compared to the FFP group
Measured: 28 days following transfusion of convP or FFP
Age and clinical frailty score
Age and clinical frailty score stratified analysis of percentage of primary endpoint following transfusion of convP versus FFP.
Measured: 28 days following transfusion of convP or FFP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start12 Oct 2020
- Primary completion1 Oct 2021
- Study completion1 Mar 2022
Why it stopped: vaccination uptake 80% in the target population/new COVID variant
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 420 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Prothya Biosolutions, ZonMw: The Netherlands Organisation for Health Research and Development, Leiden University Medical Center
- Responsible party
- Principal investigator, Bart Rijnders, Erasmus Medical Center
- Investigators
- Bart Rijnders, MD, PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04589949
- Sponsor's protocol ID
- NL74972.078.20
- Acronym
- CoV-Early
- Status last verified
- Mar 2022
- First submitted
- 12 Oct 2020
- Last updated
- 1 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Millat-Martinez P, Gharbharan A, Alemany A, Rokx C, Geurtsvankessel C, Papageorgiou G, van Geloven N, Jordans C, Groeneveld G, Swaneveld F, van der Schoot E, Corbacho-Monne M, Ouchi D, Piccolo Ferreira F, Malchair P, Videla S, Garcia Garcia V, Ruiz-Comellas A, Ramirez-Morros A, Rodriguez Codina J, Amado Simon R, Grifols JR, Blanco J, Blanco I, Ara J, Bassat Q, Clotet B, Baro B, Troxel A, Zwaginga JJ, Mitja O, Rijnders BJA; CoV-Early study group; COnV-ert study group. Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients. Nat Commun. 2022 May 11;13(1):2583. doi: 10.1038/s41467-022-29911-3.
PubMed 35546145
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Convalescent Plasma Therapy for High-risk Patients With COVID-19 in Primary Care (the CoV-Early Study)
- ClinicalTrials.gov ID
- NCT04589949
- Acronym / sponsor ID
- CoV-Early / NL74972.078.20
- Conditions
- Covid19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: vaccination uptake 80% in the target population/new COVID variant
- Enrolment
- 420 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Prothya Biosolutions, ZonMw: The Netherlands Organisation for Health Research and Development, Leiden University Medical Center
- Study start
- 12 Oct 2020 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An effective, widely available, and safe treatment that can decrease the duration, severity and fatality of COVID-19 is urgently needed. Also, in the most affected regions the pressure on health care systems including ventilator support capacity can be a limiting factor for survival. Initial studies including from our group indicate that administering convalescent plasma containing high titers of neutralizing antibodies to COVID-19 patients who are already relatively late during the disease course after hospital admission is not effective, which can be explained by high titers of autologous antibodies present in patients. Thus, the antiviral capacity of convalescent plasma is hypothesized to be best positioned early in the disease course and in patients at increased risk for a severe disease course. If effective, any treatment that decreases the need for hospital admission is very valuable but so far, no COVID-19 treatment has been shown to prevent clinical deterioration when given before patients are admitted to the hospital.
Primary objective:
To evaluate the efficacy, feasibility and safety following the administration of convalescent plasma (ConvP) as a therapy for outpatients diagnosed with COVID-19 at increased risk for an unfavourable clinical outcome and within 7 days after symptom onset.
Study design:
This trial is a nationwide multicenter, double blind, randomized controlled trial in the Netherlands. Patients will be randomized between the transfusion of 300mL of convP versus regular fresh frozen plasma (FFP).
Patient population:
Patients with polymerase chain reaction (PCR) confirmed COVID disease with less than 8 days of symptoms, age 70 or older or 50-69 years with at least 1 additional risk factor for severe COVID-19 are eligible.
Intervention:
300mL of convP with a minimum level of neutralizing antibodies.
A total of 690 patients will be included. Expected duration of accrual: 18-24 months Duration of follow up :Day 28 for the primary endpoint
Detailed description
Secondary (exploratory) objectives
- To evaluate the impact of 300mL convP on mortality
- To evaluate the impact of 300mL convP on hospital admission
- To evaluate the impact of 300mL convP on admission to ICU
- To evaluate the impact of 300mL convP on duration of symptoms
- To evaluate the impact of 300mL convP in relation to the age and clinical frailty of the patient
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ConvP | Experimental | Biological: ConvP300 mL convalescent plasma with a minimum of neutralizing antibodies |
| FFP | Active comparator | Biological: FFP300 mL Fresh Frozen plasma |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- RT-PCR-confirmed COVID-19.
- Symptomatic (e.g but not limited to fatigue, fever, cough, dyspnoea, loss of taste or smell, diarrhea, falls or confusion)
- 70 years or older OR 50-69 years and 1 or more of the risk factors described in the protocol
Key exclusion criteria (6 listed)
- Life expectancy <28 days in the opinion of the treating physician
- Patient or legal representative is unable to provide written informed consent
- Symptomatic for 8 days or more
- Being admitted to the hospital at the informed consent procedure
- Known previous history of transfusion-related acute lung injury
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ConvPAlso: convalescent plasmaInfusion 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 | Biological | ConvP |
| FFPAlso: Fresh Frozen PlasmaInfusion of thawed non-convalescent plasma Plasma will be administered according to the Erasmus Medical Center quality protocol regarding the use of blood products | Biological | FFP |
Primary outcome
Highest disease status
Time frame: 28 days following transfusion of convP or FFP
Highest disease status on the 5-point ordinal disease severity scale in the convP group will be compared with the FFP group.
5 secondary outcomes
Percentage of deaths
Time frame: 28 days following transfusion of convP or FFP
Percentage of hospital admissions
Time frame: 28 days following transfusion of convP or FFP
Percentage of ICU admissions
Time frame: 28 days following transfusion of convP or FFP
Disease duration in days of symptoms
Time frame: 28 days following transfusion of convP or FFP
Age and clinical frailty score
Time frame: 28 days following transfusion of convP or FFP
Results and safety
The study was stopped early (reason given: vaccination uptake 80% in the target population/new COVID variant). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2022.
- Derived from this study: PubMed 35546145Millat-Martinez P, Gharbharan A, Alemany A, Rokx C, Geurtsvankessel C, Papageorgiou G, van Geloven N, Jordans C, Groeneveld G, Swaneveld F, van der Schoot E, Corbacho-Monne M, Ouchi D, Piccolo Ferreira F, Malchair P, Videla S, Garcia Garcia V, Ruiz-Comellas A, Ramirez-Morros A, Rodriguez Codina J, Amado Simon R, Grifols JR, Blanco J, Blanco I, Ara J, Bassat Q, Clotet B, Baro B, Troxel A, Zwaginga JJ, Mitja O, Rijnders BJA; CoV-Early study group; COnV-ert study group. Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients. Nat Commun. 2022 May 11;13(1):2583. doi: 10.1038/s41467-022-29911-3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bart Rijnders, MD, PhD principal investigator
Erasmus Medical Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ConvP and FFP in people with Covid19, run by Erasmus Medical Center at 11 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: vaccination uptake 80% in the target population/new COVID variant). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Highest disease status (time frame: 28 days following transfusion of convP or FFP). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04589949, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2022.