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

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

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.

Study Overview

• Status: Unknown
• Conditions: COVID; ARDS, Human
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Recruiting
    • Aalborg University Hospital
    • Contact: Bodil S Rasmussen, MD, PhD
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Steffen Christensen, MD, PhD
  • Hvidovre, Denmark, 2650
    • Recruiting
    • Hvidovre Hospital
    • Contact: Klaus T Kristiansen, MD
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Thomas Strøm, MD

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment; Standard intensive care
Active Comparator: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Mortality	Assessment of mortality is considered a core outcome for trials within acute respiratory failure	Day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Need for renal replacement therapy	Renal replacement therapy includes dialysis (hemodialysis or peritoneal dialysis), hemofiltration, and hemodiafiltration.	Day 28
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
Measurement of SARS-CoV2 load	Quantification of viral load before and after treatment	Day 0 and 3

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Odense University Hospital; Aarhus University Hospital; Hvidovre University Hospital; Aalborg 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

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2020
• Primary Completion (Anticipated): April 24, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 19, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: SARS-COV2; corona virus infection; senicapoc; severe acute respiratory distress syndrome
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Respiratory Insufficiency; Respiratory Distress Syndrome
• Other Study ID Numbers: 2020-001420-34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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).
• IPD Sharing Time Frame: Data will become available following publication with no planned end date.
• IPD Sharing 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
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No