Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency (COVIPOC)

• ClinicalTrials.gov Identifier: NCT04594668
• Recruitment Status: Recruiting
• First Posted: October 20, 2020
• Last Update Posted: October 20, 2020
• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Odense University Hospital; Aalborg University Hospital; Hvidovre University Hospital
• Information provided by (Responsible Party): University of Aarhus

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 (Clinical Trial)
• Estimated Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A 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: April 24, 2020
• Estimated Primary Completion Date: April 24, 2021
• Estimated Study Completion Date: December 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 Name: ICA-17043

Outcome Measures

Primary Outcome Measures :

1. PaO2/FiO2 ratio [ Time Frame: 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 :

1. Ventilator-free days [ Time Frame: 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
2. Mortality [ Time Frame: Day 28 ]
   Assessment of mortality is considered a core outcome for trials within acute respiratory failure

Other Outcome Measures:

1. Vasopressor-free days [ Time Frame: Day 28 ]
   An infusion of a vasopressor will be defined as any continuous infusion of noradrenaline, dopamine, dobutamine, terlipressin, vasopressin, phenylephrine, and/or adrenaline
2. Sequential Organ Failure Assessment (SOFA)-score [ Time Frame: 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.
3. Need for renal replacement therapy [ Time Frame: Day 28 ]
   Renal replacement therapy includes dialysis (hemodialysis or peritoneal dialysis), hemofiltration, and hemodiafiltration.
4. Health-related quality of life (EQ-5D-5L) [ Time Frame: 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.
5. Measurement of SARS-CoV2 load [ Time Frame: Day 0 and 3 ]
   Quantification of viral load before and after treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Ulf Simonsen, MD, PhD; +4560202613; us@biomed.au.dk

Contact: Asger Granfeldt, MD, PhD; covipoc@clin.au.dk

Locations

Denmark

Aalborg University Hospital; Recruiting

Aalborg, Denmark, 9000

Contact: Bodil S Rasmussen, MD, PhD

Aarhus University Hospital; Recruiting

Aarhus, Denmark, 8000

Contact: Steffen Christensen, MD, PhD

Hvidovre Hospital; Recruiting

Hvidovre, Denmark, 2650

Contact: Klaus T Kristiansen, MD

Odense University Hospital; Recruiting

Odense, Denmark, 5000

Contact: Thomas Strøm, MD

Sponsors and Collaborators

University of Aarhus

Aarhus University Hospital

Odense University Hospital

Aalborg University Hospital

Hvidovre University Hospital

Investigators

• Principal Investigator: Steffen Christensen, MD; Aarhus University Hospital
• Principal Investigator: Thomas Strøm, MD; Odense University Hospital
• Principal Investigator: Bodil S Rasmussen, MD, PhD; Aalborg University Hospital
• Principal Investigator: Klaus T Kristiansen, MD; Hvidovre University Hospital
• Study Chair: Asger Granfeldt, MD, PhD; Aarhus University Hospital

More Information

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT04594668
• Other Study ID Numbers: 2020-001420-34
• First Posted: October 20, 2020
• Last Update Posted: October 20, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data sharing plan: Individual de-identified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data to be shared included de-identified data points in published, peer-reviewed articles. Additional, related documents will also be available (study protocol, informed consent form, statistical analysis plan).
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Data will become available following publication with no planned end date.
• Access Criteria: Access to the data sharing will be given to researchers who provide a methodologically sound proposal for any type of analysis and requires IRB/Ethics approval (if applicable). Proposal should be addressed to us@biomed.au.dk

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Aarhus:

senicapoc; severe acute respiratory distress syndrome; SARS-COV2; corona virus infection

Additional relevant MeSH terms:

Respiratory Insufficiency; Respiratory Distress Syndrome; Pulmonary Valve Insufficiency; Respiration Disorders; Respiratory Tract Diseases; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Lung Diseases