COVIPOC: Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency

Sponsor

University of Aarhus (Other)

Overall Status

Unknown status

CT.gov ID

NCT04594668

Collaborator

Aarhus University Hospital (Other), Odense University Hospital (Other), Aalborg University Hospital (Other), Hvidovre University Hospital (Other)

Enrollment

Locations

Arms

20.2

Anticipated Duration (Months)

11.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
ARDS, Human COVID	Drug: Senicapoc	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A Randomized, Open-Label, Phase II TrialA Randomized, Open-Label, Phase II Trial

Masking:

None (Open Label)

Masking Description:

Senicapoc-treated patients compared to standard treatment

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 24, 2020

Anticipated Primary Completion Date :

Apr 24, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard treatment Standard intensive care
Active Comparator: Senicapoc Senicapoc	Drug: Senicapoc The intervention will consist of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 hours Other Names: ICA-17043

Arm

Intervention/Treatment

No Intervention: Standard treatment

Standard intensive care

Active Comparator: Senicapoc

Senicapoc

Drug: Senicapoc

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

Other Names:

ICA-17043

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

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
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.
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.
Measurement of SARS-CoV2 load [Day 0 and 3]
Quantification of viral load before and after treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Aalborg University Hospital	Aalborg	Denmark	9000
2	Aarhus University Hospital	Aarhus	Denmark	8000
3	Hvidovre Hospital	Hvidovre	Denmark	2650
4	Odense University Hospital	Odense	Denmark	5000