Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency

COVID Clinical Trial

— COVIPOC  

Official title:

Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04594668
• Other study ID #: 2020-001420-34
• Status: Recruiting
• Phase: Phase 2
• Start date: April 24, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: April 2020
• Source: University of Aarhus
• Contact: Ulf Simonsen, MD, PhD
• Phone: +4560202613
• Email: us[@]biomed.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: December 31, 2021
• Est. primary completion date: April 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ARDS, Human
• COVID
• Pulmonary Valve Insufficiency
• Respiratory Distress Syndrome, Adult
• Respiratory Insufficiency

Intervention

Drug:
• Senicapoc
The intervention will consist of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 hours

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Odense University Hospital	Odense

Sponsors (5)

Lead Sponsor	Collaborator
University of Aarhus	Aalborg University Hospital, Aarhus University Hospital, Hvidovre University Hospital, Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Vasopressor-free days	An infusion of a vasopressor will be defined as any continuous infusion of noradrenaline, dopamine, dobutamine, terlipressin, vasopressin, phenylephrine, and/or adrenaline	Day 28
Other	Sequential Organ Failure Assessment (SOFA)-score	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.	Day 1, 2, 3, and 5
Other	Need for renal replacement therapy	Renal replacement therapy includes dialysis (hemodialysis or peritoneal dialysis), hemofiltration, and hemodiafiltration.	Day 28
Other	Health-related quality of life (EQ-5D-5L)	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.	Day 28
Other	Measurement of SARS-CoV2 load	Quantification of viral load before and after treatment	Day 0 and 3
Primary	PaO2/FiO2 ratio	The PaO2/FiO2 ratio will be calculated based on the arterial gas closest to the time-point of Day 3 after randomization	Day 3
Secondary	Ventilator-free days	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	Day 28
Secondary	Mortality	Assessment of mortality is considered a core outcome for trials within acute respiratory failure	Day 28