Clinical trial NCT04594668: Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency
Official title: Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: ARDS, Human
COVID
Keywords: senicapoc
severe acute respiratory distress syndrome
SARS-COV2
corona virus infection
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Odense University Hospital
name: Aalborg University Hospital
name: Hvidovre University Hospital
First posted: 2020-10-20
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Randomized, Open-Label, Phase II Trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: PaO2/FiO2 ratio
timeFrame: Day 3
Secondary outcomes:
measure: Ventilator-free days
timeFrame: Day 28
measure: Mortality
timeFrame: Day 28
Other outcomes:
measure: Vasopressor-free days
timeFrame: Day 28
measure: Sequential Organ Failure Assessment (SOFA)-score
timeFrame: Day 1, 2, 3, and 5
measure: Need for renal replacement therapy
timeFrame: Day 28
measure: Health-related quality of life (EQ-5D-5L)
timeFrame: Day 28
measure: Measurement of SARS-CoV2 load
timeFrame: Day 0 and 3
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Steffen Christensen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Thomas Strøm, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aalborg University Hospital
name: Bodil S Rasmussen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hvidovre University Hospital
name: Klaus T Kristiansen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Asger Granfeldt, MD, PhD
role: STUDY_CHAIR
References: