To assess the 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.
ID
Source
Brief title
Condition
- Viral infectious disorders
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Duration of mechanical ventilation (days) and withholding of mechanical
ventilation (%)
Secondary outcome
- not applicable -
Background summary
Up to 15% of COVID-19 patients are admitted to the hospitals with signs of
(near) respiratory failure. The CT of the chest shows extensive interstitial
pneumonia in all these cases. In this acute setting however, PCR analyses of
nasopharynx swabs are frequently negative for Sars-CoV-2. Our hypothesis is
that these critical ill 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 objective
To assess the 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.
Study design
Multicentre prospective placebo-controlled interventional clinical trial.
Intervention
Bolus alkaline phosphatase of 1000iU; followed by 9000 iU the same day. For the
3 consecutive days 10.000iU/day on top of regular care (all patients)
Study burden and risks
Alkaline phosphatase (AP) is an endogenous protein/enzyme. RESCAP is AP derived
from bovine intestinal cells and processed for clinical application. Critically
ill patients with COVID-19 are treated with AP for 4 consecutive days in this
study. In 3 other (Dutch) clinical trials, no treatment-related side effects
were reported (see DSUR). RESCAP has the potential to reduce (pulmonary)
complications in critically ill COVID-19 patients. In the current APhIRI
clinical trial running in Amsterdam UMC (prevention of ischemia-reperfusion
injury in renal transplantation), the intervention was considered as low-risk
because of the small amount of protein that is infused (<10 mg/24 hours) and no
observed IMP related side effects in other clinical trials.
Vondellaan 13
Beverwijk 1942 LE
NL
Vondellaan 13
Beverwijk 1942 LE
NL
Listed location countries
Age
Inclusion criteria
- Sars-CoV-2 infection based on: highly clinical suspicion on admission and/or
positive PCR test on naso-pharynx swab or sputum and/or a CT imaging of the
chest compatible with COVID-19 + type 1 or type 2 respiratory failure needing
supplemental oxygen that indicates airway support or ICU admittance and meeting
any of the following criteria: .
- SpO2 <90% or PaO2/FiO2 < 200 mmHg
- Clinical evidence of respiratory distress (RR > 25 breaths/minute)
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 a 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) Patients who are
receiving chronic high doses (equivalent to prednisone/prednisolone 0.5
mg/kg/day) steroids therapy immediately prior to recruitment exceeding 2 weeks
of treatment. This means dexamethasone 6 mg once daily serving as treatment for
severe COVID-19 is not an exclusion criterion.
- Patients with active haematological malignancy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001714-38-NL |
| CCMO | NL73891.029.20 |
| Other | NL8578 |