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ID
Source
Brief title
Health condition
COVID-19
Sponsors and support
Intervention
Outcome measures
Primary outcome
Duration of mechanical ventilation
Secondary outcome
(1) ICU Mortality
(2) Number (%) of patients with acute kidney injury (AKI) stage 2/3 (KDIGO criteria)
(3) Number (%) of ventilated patients
(4) Number (%) of patients in need for reintubation
(5) Safety (according to chapter 8)
(6) Values of inflammatory markers (e.g. macrophages, neutrophils, lymphocytes and their inflammatory products (TNF-α, IL-6, IL-8, IL-10))
Background summary
Our hypothesis is that critical ill COVID-19 patients suffer more from their own immune response against the virus, than from the viral infection itself. Alkaline phosphatase (RESCAP®) has proven to reduce SIRS reactions by neutralizing the inflammatory response in various medical conditions, like sepsis induced acute kidney injury and ischemia-reperfusion reactions in cardiothoracic surgery. Furthermore, endogenous alkaline phosphatase (AP) is highly expressed on type II lung alveolar (surfactant producing) cells and is thought to stabilize the alveolar barrier. In acute inflammation, endogenous AP is lost from the cells after binding to its substrate. Replenishing AP might restore the alveolar barrier and combat subsequent SIRS and secondary organ failure.
The objective is to assess the safety and preliminary efficacy of AP in reducing the inflammatory reaction in COVID-19 patients and thereby shorten time on mechanical ventilation or prevent the need for mechanical ventilation in COVID-19 patients.
This will be done in a randomised multicentre prospective interventional clinical trial.
All COVID-19 patients with an indication for admittance to the ICU department will be included and will (after informed consent) be rondomised to receive a bolus of alkaline phosphatase of 1000iU, followed by 9000 iU the same day. For the 3 consecutive days 10.000iU/day on top of regular care.
Main study parameters/endpoints:
(1) Duration of mechanical ventilation
(2) ICU mortality
(3) Number (%) of patients with acute kidney injury (AKI) stage 2/3 (KDIGO)
(4) Concentration of pro-inflammatory cytokines
Study objective
Our hypothesis is that critical ill COVID-19 patients suffer more from their own immune response against the virus, than from the viral infection itself. Alkaline phosphatase (RESCAP®) has proven to reduce SIRS reactions by neutralizing the inflammatory response in various medical conditions, like sepsis induced acute kidney injury and ischemia-reperfusion reactions in cardiothoracic surgery. Furthermore, endogenous alkaline phosphatase (AP) is highly expressed on type II lung alveolar (surfactant producing) cells and is thought to stabilize the alveolar barrier. In acute inflammation, endogenous AP is lost from the cells after binding to its substrate. Replenishing AP might restore the alveolar barrier and combat subsequent SIRS and secondary organ failure.
Study design
1 year
Intervention
All COVID-19 patients with an indication for admittance to the ICU department will be included and will (after informed consent) be rondomised to receive a bolus of alkaline phosphatase of 1000iU, followed by 9000 iU the same day. For the 3 consecutive days 10.000iU/day on top of regular care.
Inclusion criteria
Patients with proved or considered Sars-CoV-2 infection admitted to the ICU with type 1 or 2 respiratory failure despite supplemental oxygen.
Sars-CoV-2 infection based on: highly clinical suspicion on admission and/or positive PCR test on nasopharynx swab or sputum and/or a CT imaging of the chest compatible with COVID-19 + type 1 or type 2 respiratory failure despite supplemental oxygen that indicates airway support/ICU admittance and meeting any of the following criteria: .
- SpO2 <90% or PaO2 < 60 mmHg despite FiO2 >60%
- Clinical evidence of respiratory distress (RR > 25 breaths/minute)
- Respiratory acidosis (pH< 7.35)
Exclusion criteria
- Inclusion in another interventional clinical trial
- Age < 18
- Age > 80
- Patients who are pregnant or lactating
- Patients expected to have fatal disease within 24 hours
- Patients who are already on dialysis (Renal Replacement Therapy, RRT) or a decision has been made to initiate RRT within 24 hours after planned start of study drug administration
- Patients who have advanced chronic liver disease confirmed by a Child-Pugh C
- Patients who are having an known history of immune system that has been impaired by disease, such as patients with HIV and with a CD4 count of less than 200 cells/mm, neutropenic patients (<0.5 x 109/l) or medical treatment with immunosuppressive effects
- Patients with active haematological malignancy
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8578 |
| Other | METC VUMC : METC2020248 |