ARDS, Human, COVID
Conditions
Keywords
senicapoc, severe acute respiratory distress syndrome, SARS-COV2, corona virus infection
Brief summary
SARS-CoV-2, one of a family of human coronaviruses, was initially identified in December 2019 in Wuhan city. This new coronavirus causes a disease that has now been named COVID-19. The virus has subsequently spread throughout the world and was declared a pandemic by the World Health Organisation on 11th March 2020. As of April 1, 2020, there are 874.081 numbers of confirmed cases with 43.290 fatalities. There is no approved therapy for COVID-19 and the current standard of care is supportive treatment. Key markers implying a fatal outcome are acute respiratory distress syndrome (ARDS)-like disease with pronounced dyspnea, hypoxia and radiological changes in the lung. Senicapoc improves oxygenation and reduces fluid retention, inflammation, and bleeding in the lungs of mice with ARDS-like disease. In cells, there is an antiviral effect of senicapoc.
Detailed description
The investigators discovered that in an animal model with a knockout of a potassium channel with intermediate conductance (KCa3.1), the knockout protected against lung damage and accumulation of liquid in the lung. In subsequent studies, the investigators have developed a mouse model showing that genetic deletion of the KCa3.1 channels and senicapoc, a blocker of KCa3.1 channels, protects against the accumulation of liquid in the lung. Moreover, senicapoc treatment possesses anti-inflammatory effects illustrated as lower leukocyte accumulation inside the lungs after injury. Importantly, it also increases the FiO2/PaO2 ratio (ratio of inhaled to blood oxygen), hence preserving lung function in mice with an ARDS-like disease. In addition, there is evidence that senicapoc has antiviral properties. Aarhus University has patented senicapoc for use in the treatment of acute respiratory disease. In this case, respiratory disease is caused by an infection with a coronavirus. Senicapoc has been developed for the treatment of sickle cell disease and has been administered to 500 patients without observation of major treatment-related adverse effects.
Interventions
DRUGSenicapoc
The intervention will consist of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 hours
Sponsors
Aarhus University Hospital
Odense University Hospital
Aalborg University Hospital
Hvidovre University Hospital
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Senicapoc-treated patients compared to standard treatment
Intervention model description
A Randomized, Open-Label, Phase II Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* COVID-19 positive * Age ≥18 years * Respiratory insufficiency * ICU admission
Exclusion criteria
* Severe heart failure (ejection fraction \< 30%) * Severe renal insufficiency (eGFR \< 30 mL/min/1.73m2) * Severe hemodynamic instability (noradrenalin dose \> 0.3 μg/kg/min) * Prior enrollment in the trial * Pregnancy * Allergy to senicapoc * Inability to take enteral medication * More than 24 hours since ICU admission * Limitations of care * Anticipated death within 24 hours
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PaO2/FiO2 ratio | Day 3 | The PaO2/FiO2 ratio will be calculated based on the arterial gas closest to the time-point of Day 3 after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free days | Day 28 | Ventilator-free days will be defined as the number of days (or proportion of days) within the first 28 days after randomization where the patient is alive and not on invasive mechanical ventilation |
| Mortality | Day 28 | Assessment of mortality is considered a core outcome for trials within acute respiratory failure |
Other
| Measure | Time frame | Description |
|---|---|---|
| Health-related quality of life (EQ-5D-5L) | Day 28 | Health-related quality of life (EQ-5D-5L) in 5 dimensions and 5 levels (1-5) with 1 as worst and 5 as best level in each dimension. At day 28 EQ-5D-5L will be assessed via telephone communication with the patient or a surrogate. The telephone interview will be semi-structured and based on the EQ-5D-5L questionnaire. The interview will be conducted by a centrally-located and trained member of the research team according to detailed standard operating procedures. In case the patient is still in the hospital, this interview will be face-to-face. |
| Vasopressor-free days | Day 28 | An infusion of a vasopressor will be defined as any continuous infusion of noradrenaline, dopamine, dobutamine, terlipressin, vasopressin, phenylephrine, and/or adrenaline |
| Measurement of SARS-CoV2 load | Day 0 and 3 | Quantification of viral load before and after treatment |
| Sequential Organ Failure Assessment (SOFA)-score | Day 1, 2, 3, and 5 | The Sequential Organ Failure Assessment (SOFA)-score 1-4 will be used with 1 as best and 4 as worst score. The SOFA score is a validated and widely used measure of organ failure assessing the respiratory, nervous, cardiovascular, hepatic, coagulation, and renal systems. The sub scores as well as the overall SOFA score will be assessed. The calculation of the SOFA score will be based on available clinical and laboratory data. Laboratory and clinical data closest to the given time point will be used. If a given component (e.g. bilirubin) is not available, it will be assumed to be within normal ranges. |
| Need for renal replacement therapy | Day 28 | Renal replacement therapy includes dialysis (hemodialysis or peritoneal dialysis), hemofiltration, and hemodiafiltration. |
Countries
Denmark
Contacts
Primary ContactUlf Simonsen, MD, PhD
Backup ContactAsger Granfeldt, MD, PhD
Outcome results
None listed