Covid19Phase 2CONFIDENTNCT04558476
Efficacy of CONvalescent Plasma in Patients With COVID-19 Treated With Mechanical Ventilation
A Phase 2 study testing Convalescent Plasma in people with Covid19 and Mechanical Ventilation Complication, run by University of Liege at 17 sites in Belgium.
Trial summary
The principal objective of the CONFIDENT trial is to assess the efficacy of two units (400-500 mL in total) of convalescent plasma, as compared to Standard of Care (SoC), to reduce day-28 mortality in patients with SARS-CoV-2 pneumonia who require mechanical ventilation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Mechanical Ventilation Complication, Corona Virus Infection
- What is being tested?
- Convalescent Plasma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 475 participants
- Where
- 17 sitesBelgium
- Study dates
- 11 Sep 2020to 9 Mar 2023
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age at least 18 years
- hospitalization in an intensive care unit participating to the study
- medical diagnosis with SARS-CoV-2 pneumonia as defined by both:
- extended interstitial pneumonia on CT scan or a chest X-ray, consistent with viral pneumonia, within 10 days prior to inclusion
- Positive result of SARS-CoV-2 PCR test, or any emerging and validated diagnostic laboratory test for COVID-19, within 15 days prior to inclusion
- under mechanical ventilation administered through an endotracheal tube, for less than 5 days
- prior Clinical Frailty Scale < 6.
- written consent of the patient, or - if impossible - of a relative acting as the legal representative, or - if impossible - of a physician from a non-participating department of the same hospital acting as an impartial witness .
Who cannot join
- Pregnancy
- Prior episode of transfusion-related side effect
- Medical decision to limit therapy
- Current participation in another trial testing a COVID-19 therapy
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Belgium17 sites
OLVZ Aalst
Aalst, 9300
UZ Antwerpen
Antwerp, 2650
Imelda ZH Bonheiden
Bonheiden, 2820
CHU Saint Pierre
Brussels, 1000
Erasme
Brussels, 1070
UZ Brussel
Brussels, 1090
CHU Charleroi Marie Curie
Charleroi, 6042
AZ Sint Blasius
Dendermonde, 9200
UZ Gent
Ghent, 9000
AZ Groeningen Kortrijck
Kortrijk, 8500
UC Louvain
Leuven, 1200
CHR Citadelle
Liège, 4000
CHU Liège
Liège, 4000
Clinique Saint Pierre Ottignies
Ottignies, Brabant Wallon, 1340
AZ Delta
Roeselare, 8800
Centre Hospitalier Wallonie Picarde
Tournai, Hainaut, 7500
CHU UCL Namur-Godinne
Yvoir, 5530
About this study
Official title: A Multicenter Randomized Trial to Assess the Efficacy of CONvalescent Plasma Therapy in Patients With Invasive COVID-19 and Acute Respiratory Failure Treated With Mechanical Ventilation: the CONFIDENT Trial
The principal objective of the CONFIDENT trial is to assess the efficacy of two units (400-500 mL in total) of convalescent plasma, as compared to Standard of Care (SoC), to reduce day-28 mortality in patients with SARS-CoV-2 pneumonia who require mechanical ventilation.
Read the detailed description
Design : multicenter randomized openlabel, phase II trial.
Number of patients to include : 500 (250 with plasma, 250 without plasma).
The principal objective is to assess the efficacy of the treatment to reduce day-28 mortality in patients with SARS-CoV-2 pneumonia who require mechanical ventilation.
Hypothesis: Passive immunization with plasma collected from patients having contracted COVID-19 and developed specific antibodies may alleviate symptoms and viral load of SARS-CoV-2 and reduce mortality.
The patients will receive currently accepted standard of care for both COVID-19 and usual organ dysfunctions observed in such cases. half the patients will be administered either Convalescent plasma, depending on the randomization process. All patients will be followed-up for one year after inclusion. The study will be considered either positive or negative, based on the principal objective. This means that the product convalescent plasme will be considered effective if mortality at day 28 is lower is patients treated with convalescent plasma than without it. The follow-up will allow to assess a series of secondary objectives, addressing the evolution of organ failures, viral infection, inflammatory response and long-term physical of psychological impact of COVID-19. Interim analyses will be performed every 100 patients included in order to stop the trial if an exceptionally good or bad result is observed, to prevent using or not using the product appropriately in further patients. These analyses will be supervised by an independent committee.
The choice to include only those patients under mechanical ventilation for severe respiratory failure makes this study different from other trials testing convalescent plasma, as most trial include less severe patients.
- Conditions
- Covid19, Mechanical Ventilation Complication, Corona Virus Infection, Respiratory Failure, SARS (Severe Acute Respiratory Syndrome)
- Being tested
- Convalescent Plasma, Standard of Care
- Keywords
- Covid 19, Convalescent plasmatherapy, SARS Cov-2 pneumonia
- Medical subject headings
- COVID-19, Coronavirus Infections, Respiratory Insufficiency, Severe Acute Respiratory Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Convalescent PlasmaBiological
2 units of convalescent plasma
Standard of CareOther
Gold Standards
| Study group | Role | What they receive |
|---|---|---|
| Convalescent Plasma | Experimental | 2 units of plasma ( 400-500ml) from 2 different donnors duration of treatment =2 h Receives: Biological: Convalescent Plasma |
| Standard of care | Other | Standard of care according the last gold standards Receives: Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vital status
dead or alive
Measured: at day 28
Secondary outcomes (18)
day 90 mortality
dead or alive
Measured: at day 90
number of ventilator-free days at day 28
to assess the ventilator free days
Measured: at day 28
number of renal replacement therapy free days at day 28
to assess the number of renal replacement therapy free days
Measured: at day 28
number of vasopressors free-days at day 28
to assess the number of vasopressors free-days
Measured: at day 28
use of ECMO before day 28
to assess if ECMO was required
Measured: till day 28
value of the SOFA score at days 7, 14 and 28
to assess the value of SOFA score
Measured: Day 1, 7, 14, 28
changes in SOFA scores (delta SOFA) over 7, 14 and 28 days
to assess the changes in SOFA scores (delta SOFA)
Measured: Day 7, 14 and 28 days
assessment of the SARS-CoV-2 viral load
assessment of the SARS-CoV-2 viral load, expressed as cycle threshold, [2] in the tracheal aspirates (for intubated patients) or nasopharyngeal swabs (for extubated patients) at days 7, 14 and 28
Measured: Days 7, 14 and 28
blood C reactive protein (CRP) concentration
to assess the concentrations of C reactive protein (CRP)
Measured: Days 7, 14 and 28
ferritin concentration
to assess the concentration of ferritin
Measured: Days 7, 14 and 28
lymphocyte count
to assess the count of lymphocyte
Measured: Days 7, 14 and 28
length of stay in the acute care hospital
to assess the lenght of stay in the acute care
Measured: through study completion, 1 year
location of the patient
to assess the location of the patient : acute care hospital, post acute care hospital, long-term residency, home
Measured: Day 90
Katz Index of independence in Activity Day Living functional score
to assess the Activity Day Living functional Min value: 0 = Low (patient very dependent) Max value: 6 = High (patient independent)
Measured: Day 90 and 365
Hospital Anxiety and Depression Scale (HADS)
to evaluate the anxiety-depression For each item 0-7 : Normal 8-10 : Bordeline abnormal (borderline case) 11-21 : Abnormal case
Measured: Day 90 and 365
Quality of life scale EQ-5D-5L
The EQ-5D-5L is composed of - the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Each level corresponds to 1-digit number expressing the level selected for that dimension.
The EQ VAS corresponds to a 20 cm vertical, visual analogue scale raging from 'the best health you can imagine' to 'the worst health you can imagine'.
Measured: Day 90 and 365
Transfusion related adverse events
to assess the transfusion related adverse events
Measured: till 28 days
Determine the type of concommittent inflammatory response
assess clusters based on the profile of cytokines, chemokines and cell adhesion markers
Measured: till 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2020
- Study start11 Sep 2020
- Primary completion9 Apr 2022
- Study completion9 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 475 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liege
- Sponsor type
- University, hospital or other
- Collaborators
- KCE Belgian Healthcare Knowledge Centre
- Responsible party
- Principal investigator, Misset Benoit, University of Liege
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04558476
- Sponsor's protocol ID
- 2020-003102-31
- Acronym
- CONFIDENT
- Status last verified
- Oct 2024
- First submitted
- 14 Sep 2020
- Last updated
- 29 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Rousseau AF, Dardenne N, Bertrand A, Piagnerelli M, Hoste E, Grimaldi D, Michaux I, De Waele E, Dumoulin A, Jorens PG, van der Hauwaert E, Vallot F, Lamote S, Swinnen W, De Schryver N, Fraipont V, de Mey N, Dauby N, Layios N, Mesland JB, Donneau AF, Laterre PF, Misset B. Health-related quality of life trajectories one year after COVID-19-induced ARDS: A secondary analysis of the CONFIDENT trial. Ann Intensive Care. 2026 Jan 16;16:100009. doi: 10.1016/j.aicoj.2025.100009. eCollection 2026.
PubMed 41788496Misset B, Diep AN, Bertrand A, Piagnerelli M, Hoste E, Michaux I, De Waele E, Dumoulin A, Jorens PG, van der Hauwaert E, Vallot F, Swinnen W, De Schryver N, de Mey N, Layios N, Mesland JB, Robinet S, Cavalier E, Donneau AF, Moutschen M, Laterre PF. Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial. Ann Intensive Care. 2024 Oct 21;14(1):160. doi: 10.1186/s13613-024-01392-1.
PubMed 39432177Misset B, Piagnerelli M, Hoste E, Dardenne N, Grimaldi D, Michaux I, De Waele E, Dumoulin A, Jorens PG, van der Hauwaert E, Vallot F, Lamote S, Swinnen W, De Schryver N, Fraipont V, de Mey N, Dauby N, Layios N, Mesland JB, Meyfroidt G, Moutschen M, Compernolle V, Gothot A, Desmecht D, Taveira da Silva Pereira MI, Garigliany M, Najdovski T, Bertrand A, Donneau AF, Laterre PF. Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients. N Engl J Med. 2023 Oct 26;389(17):1590-1600. doi: 10.1056/NEJMoa2209502. Epub 2023 Oct 25.
PubMed 37889107Misset B, Hoste E, Donneau AF, Grimaldi D, Meyfroidt G, Moutschen M, Compernolle V, Gothot A, Desmecht D, Garigliany M, Najdovski T, Laterre PF. A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol. BMC Pulm Med. 2020 Dec 7;20(1):317. doi: 10.1186/s12890-020-01361-x.
PubMed 33287790
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Trial to Assess the Efficacy of CONvalescent Plasma Therapy in Patients With Invasive COVID-19 and Acute Respiratory Failure Treated With Mechanical Ventilation: the CONFIDENT Trial
- ClinicalTrials.gov ID
- NCT04558476
- Acronym / sponsor ID
- CONFIDENT / 2020-003102-31
- Conditions
- Covid19, Mechanical Ventilation Complication, Corona Virus Infection, Respiratory Failure, SARS (Severe Acute Respiratory Syndrome)
- Keywords
- Covid 19, Convalescent plasmatherapy, SARS Cov-2 pneumonia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 475 participants (actual)
- Lead sponsor
- University of LiegeUniversity, hospital or other
- Collaborators
- KCE Belgian Healthcare Knowledge Centre
- Study start
- 11 Sep 2020 (actual)
- Primary completion
- 9 Apr 2022 (actual)
- Study completion
- 9 Mar 2023 (actual)
- First posted
- 22 Sep 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.
The principal objective of the CONFIDENT trial is to assess the efficacy of two units (400-500 mL in total) of convalescent plasma, as compared to Standard of Care (SoC), to reduce day-28 mortality in patients with SARS-CoV-2 pneumonia who require mechanical ventilation.
Detailed description
Design : multicenter randomized openlabel, phase II trial.
Number of patients to include : 500 (250 with plasma, 250 without plasma).
The principal objective is to assess the efficacy of the treatment to reduce day-28 mortality in patients with SARS-CoV-2 pneumonia who require mechanical ventilation.
Hypothesis: Passive immunization with plasma collected from patients having contracted COVID-19 and developed specific antibodies may alleviate symptoms and viral load of SARS-CoV-2 and reduce mortality.
The patients will receive currently accepted standard of care for both COVID-19 and usual organ dysfunctions observed in such cases. half the patients will be administered either Convalescent plasma, depending on the randomization process. All patients will be followed-up for one year after inclusion. The study will be considered either positive or negative, based on the principal objective. This means that the product convalescent plasme will be considered effective if mortality at day 28 is lower is patients treated with convalescent plasma than without it. The follow-up will allow to assess a series of secondary objectives, addressing the evolution of organ failures, viral infection, inflammatory response and long-term physical of psychological impact of COVID-19. Interim analyses will be performed every 100 patients included in order to stop the trial if an exceptionally good or bad result is observed, to prevent using or not using the product appropriately in further patients. These analyses will be supervised by an independent committee.
The choice to include only those patients under mechanical ventilation for severe respiratory failure makes this study different from other trials testing convalescent plasma, as most trial include less severe patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Convalescent Plasma | Experimental | Biological: Convalescent Plasma2 units of plasma ( 400-500ml) from 2 different donnors duration of treatment =2 h |
| Standard of care | Other | Other: Standard of CareStandard of care according the last gold standards |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- age at least 18 years
- hospitalization in an intensive care unit participating to the study
- medical diagnosis with SARS-CoV-2 pneumonia as defined by both:
- under mechanical ventilation administered through an endotracheal tube, for less than 5 days
- prior Clinical Frailty Scale < 6.
Key exclusion criteria (4 listed)
- Pregnancy
- Prior episode of transfusion-related side effect
- Medical decision to limit therapy
- Current participation in another trial testing a COVID-19 therapy
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 |
|---|---|---|
| Convalescent Plasma2 units of convalescent plasma | Biological | Convalescent Plasma |
| Standard of CareGold Standards | Other | Standard of care |
Primary outcome
Vital status
Time frame: at day 28
dead or alive
18 secondary outcomes
day 90 mortality
Time frame: at day 90
number of ventilator-free days at day 28
Time frame: at day 28
number of renal replacement therapy free days at day 28
Time frame: at day 28
number of vasopressors free-days at day 28
Time frame: at day 28
use of ECMO before day 28
Time frame: till day 28
value of the SOFA score at days 7, 14 and 28
Time frame: Day 1, 7, 14, 28
changes in SOFA scores (delta SOFA) over 7, 14 and 28 days
Time frame: Day 7, 14 and 28 days
assessment of the SARS-CoV-2 viral load
Time frame: Days 7, 14 and 28
blood C reactive protein (CRP) concentration
Time frame: Days 7, 14 and 28
ferritin concentration
Time frame: Days 7, 14 and 28
lymphocyte count
Time frame: Days 7, 14 and 28
length of stay in the acute care hospital
Time frame: through study completion, 1 year
location of the patient
Time frame: Day 90
Katz Index of independence in Activity Day Living functional score
Time frame: Day 90 and 365
Hospital Anxiety and Depression Scale (HADS)
Time frame: Day 90 and 365
Quality of life scale EQ-5D-5L
Time frame: Day 90 and 365
Transfusion related adverse events
Time frame: till 28 days
Determine the type of concommittent inflammatory response
Time frame: till 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2024.
- Derived from this study: PubMed 41788496Rousseau AF, Dardenne N, Bertrand A, Piagnerelli M, Hoste E, Grimaldi D, Michaux I, De Waele E, Dumoulin A, Jorens PG, van der Hauwaert E, Vallot F, Lamote S, Swinnen W, De Schryver N, Fraipont V, de Mey N, Dauby N, Layios N, Mesland JB, Donneau AF, Laterre PF, Misset B. Health-related quality of life trajectories one year after COVID-19-induced ARDS: A secondary analysis of the CONFIDENT trial. Ann Intensive Care. 2026 Jan 16;16:100009. doi: 10.1016/j.aicoj.2025.100009. eCollection 2026.
- Derived from this study: PubMed 39432177Misset B, Diep AN, Bertrand A, Piagnerelli M, Hoste E, Michaux I, De Waele E, Dumoulin A, Jorens PG, van der Hauwaert E, Vallot F, Swinnen W, De Schryver N, de Mey N, Layios N, Mesland JB, Robinet S, Cavalier E, Donneau AF, Moutschen M, Laterre PF. Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial. Ann Intensive Care. 2024 Oct 21;14(1):160. doi: 10.1186/s13613-024-01392-1.
- Derived from this study: PubMed 37889107Misset B, Piagnerelli M, Hoste E, Dardenne N, Grimaldi D, Michaux I, De Waele E, Dumoulin A, Jorens PG, van der Hauwaert E, Vallot F, Lamote S, Swinnen W, De Schryver N, Fraipont V, de Mey N, Dauby N, Layios N, Mesland JB, Meyfroidt G, Moutschen M, Compernolle V, Gothot A, Desmecht D, Taveira da Silva Pereira MI, Garigliany M, Najdovski T, Bertrand A, Donneau AF, Laterre PF. Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients. N Engl J Med. 2023 Oct 26;389(17):1590-1600. doi: 10.1056/NEJMoa2209502. Epub 2023 Oct 25.
- Derived from this study: PubMed 33287790Misset B, Hoste E, Donneau AF, Grimaldi D, Meyfroidt G, Moutschen M, Compernolle V, Gothot A, Desmecht D, Garigliany M, Najdovski T, Laterre PF. A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol. BMC Pulm Med. 2020 Dec 7;20(1):317. doi: 10.1186/s12890-020-01361-x.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Convalescent Plasma in people with Covid19 and Mechanical Ventilation Complication, run by University of Liege at 17 sites in Belgium.
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 8 inclusion and 4 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: finished, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Belgium. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Vital status (time frame: at day 28). 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 NCT04558476, which also lists 4 linked publications.
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 29 Oct 2024.