Corona Virus Infection, Covid19, Mechanical Ventilation Complication, Respiratory Failure, SARS (Severe Acute Respiratory Syndrome)
Conditions
Keywords
Covid 19, Convalescent plasmatherapy, SARS Cov-2 pneumonia
Brief 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.
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.
Interventions
BIOLOGICALConvalescent Plasma
2 units of convalescent plasma
OTHERStandard of Care
Gold Standards
Sponsors
KCE Belgian Healthcare Knowledge Centre
University of Liege
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 .
Exclusion criteria
* Pregnancy * Prior episode of transfusion-related side effect * Medical decision to limit therapy * Current participation in another trial testing a COVID-19 therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vital status | at day 28 | dead or alive |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| number of ventilator-free days at day 28 | at day 28 | to assess the ventilator free days |
| number of renal replacement therapy free days at day 28 | at day 28 | to assess the number of renal replacement therapy free days |
| number of vasopressors free-days at day 28 | at day 28 | to assess the number of vasopressors free-days |
| use of ECMO before day 28 | till day 28 | to assess if ECMO was required |
| value of the SOFA score at days 7, 14 and 28 | Day 1, 7, 14, 28 | to assess the value of SOFA score |
| changes in SOFA scores (delta SOFA) over 7, 14 and 28 days | Day 7, 14 and 28 days | to assess the changes in SOFA scores (delta SOFA) |
| assessment of the SARS-CoV-2 viral load | Days 7, 14 and 28 | 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 |
| blood C reactive protein (CRP) concentration | Days 7, 14 and 28 | to assess the concentrations of C reactive protein (CRP) |
| day 90 mortality | at day 90 | dead or alive |
| lymphocyte count | Days 7, 14 and 28 | to assess the count of lymphocyte |
| length of stay in the acute care hospital | through study completion, 1 year | to assess the lenght of stay in the acute care |
| location of the patient | Day 90 | to assess the location of the patient : acute care hospital, post acute care hospital, long-term residency, home |
| Katz Index of independence in Activity Day Living functional score | Day 90 and 365 | to assess the Activity Day Living functional Min value: 0 = Low (patient very dependent) Max value: 6 = High (patient independent) |
| Hospital Anxiety and Depression Scale (HADS) | Day 90 and 365 | to evaluate the anxiety-depression For each item 0-7 : Normal 8-10 : Bordeline abnormal (borderline case) 11-21 : Abnormal case |
| Quality of life scale EQ-5D-5L | Day 90 and 365 | 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'. |
| Transfusion related adverse events | till 28 days | to assess the transfusion related adverse events |
| Determine the type of concommittent inflammatory response | till 28 days | assess clusters based on the profile of cytokines, chemokines and cell adhesion markers |
| ferritin concentration | Days 7, 14 and 28 | to assess the concentration of ferritin |
Countries
Belgium
Outcome results
None listed