Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000067875
Ethics application status
Approved
Date submitted
11/01/2021
Date registered
27/01/2021
Date last updated
27/01/2021
Date data sharing statement initially provided
27/01/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of the safety and tolerability of inhaled aerosolised ethanol in adult volunteers for COVID-19
Scientific title
A Phase I Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled Aerosolised Ethanol for COVID-19 disease in Healthy Adult Volunteers and Adults with Underlying Lung Disease
Secondary ID [1] 302078 0
COVINHAL-01
Universal Trial Number (UTN)
Trial acronym
COVINHAL-01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 (SARS-CoV-2) 318686 0
Condition category
Condition code
Infection 316697 316697 0 0
Other infectious diseases
Respiratory 317660 317660 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Testing for safety and tolerability will be performed at one visit where participants will continuously inhale aerosolised ethanol delivered using a closed circuit nebuliser system specifically designed with an inflatable / deflatable reservoir, extension tubing, and a viral filter on the exhalation arm. This maximises delivery efficiency (particularly for volatile fluids) and minimises aerosol loss during nebulisation thus protecting nearby personnel from exposure to potentially toxic drug and exhaled viral particles. The aerosol is delivered first to the upper airways via a nasal mask for 10 minutes followed by oral inhalation to the lower airway for 30 minutes with a 3-5 minute break in between for equipment changeover and testing. While previous studies support that adverse events and discomfort with oral inhalation to the lower airway are minimal and limited mainly to mild transient cough in a few patients, upper airway discomfort with exposure to high ethanol concentrations can be significant in some. This will therefore be alleviated by topical nasal mucosal analgesia using cophenylcaine 5% nasal spray (3 sprays each nostril - self-administered under guidance) together with cophenylcaine 3ml nebulised through a nasal mask by study staff to reach the posterior naso-pharyngeal area 30 minutes prior to ethanol nasal delivery. Upper and lower airway inhalation of aerosolised ethanol will be repeated 2 hours apart for a total of 3 doses with 3 different concentrations (40%, 60% and then 80% ethanol). All doses will be administered by a trained nurse under the supervision of a respiratory physician. Interruptions caused by the participant to upper or lower airway inhalation during dosing will be recorded together with the reasons for the interruption, the time period, and the subsequent action taken. Participants can choose to discontinue the study at any stage.
Intervention code [1] 318376 0
Treatment: Drugs
Intervention code [2] 319480 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324827 0
To assess the tolerability of upper and lower airway inhalation of aerosolized ethanol at doses of 40%, 60% or 80% v/v in water. Tolerability will be assessed by the collection of adverse events and completion of a questionnaire which has been specifically designed for this study to collect data on the level of tolerability and comfort of inhaling ethanol
Timepoint [1] 324827 0
Adverse events will be collected continuously through Day 1 (Test day) from pre-dosing until discharge with the questionnaire completed 15 minutes after the third and final dosing. Thereafter adverse events will be collected at the Day 2 visit and Day 8 phone call. In between and up to Day 8, participants are encouraged to self report any adverse events considered possibly related to study drug by contacting the study team.
Primary outcome [2] 324828 0
To assess the safety of upper and lower airway inhalation of aerosolized ethanol at doses of 40%, 60% or 80% v/v in water. Safety will be assessed by the collection of safety data including adverse events, vital signs, ECG, physical exams (including neurological and respiratory assessments), spirometry, blood ethanol levels and clinical laboratory tests.
Timepoint [2] 324828 0
Standard safety and exploratory blood tests will be performed on Day 1 pre-dosing and 1 hour after the final dose, and on Day 2, 18 hours after the final dose.
Blood Alcohol Concentration (BAC) will be measured by both breathalyser and blood sampling before, at the end of and 15 minutes after each dosing.
On Day 1, physical examinations (selected neurological and cardio-respiratory), and clinical testing, including vital signs, 12 lead ECG and spirometry will be performed at strategic time points before, during, and post each dose.
Safety will also be assessed during the follow-up visit on Day 2 and the follow-up phone call on Day 8.
Secondary outcome [1] 385878 0
Composite outcome:
Compliance and comfort levels with the delivery circuit as reported by participants throughout testing and afterwards by a questionnaire specifically designed for this study to assess the circuit's comfort, efficiency and user-friendliness.
Timepoint [1] 385878 0
Measured continually throughout dosing on Day 1 and via questionnaire specifically designed for the study 15 minutes after the final dose.
Secondary outcome [2] 385879 0
Environmental ethanol levels measured by infra-red spectroscope
Timepoint [2] 385879 0
Before, fifteen minutes into each dosing and at the end of dosing
Secondary outcome [3] 388872 0
Exploratory outcome: Ethanol levels in nasal secretions as measured by colorimetric assay
Timepoint [3] 388872 0
Immediately after each nasal dosing period on Day 1
Secondary outcome [4] 388873 0
Exploratory Outcome: Pharmacodynamic Assessment of Inflammatory markers: cytokines IL-6 and TNF-alpha using ELISA serum assay
Timepoint [4] 388873 0
Pre-dose, one hour following last dose and 24 hours post last dose
Secondary outcome [5] 388874 0
Exploratory Outcome: Assessment of urinary alcohol metabolite levels as measured by colorimetric assay
Timepoint [5] 388874 0
Single spot urine pre-dosing and pooled urine collected from start of dosing until 1 hour after the final dose
Secondary outcome [6] 389118 0
Exploatory Outcome: Evaluation of un-absorbed ethanol vapour being exhaled as measured by colorimetric assay
Timepoint [6] 389118 0
Immediately following each dosing
Secondary outcome [7] 391031 0
Exploratory outcome:
Ethanol levels in sputum as measured by colorimetric assay
Timepoint [7] 391031 0
After each lower airway dosing period on Day 1

Eligibility
Key inclusion criteria
1. Able to understand, give consent, and comply with all scheduled study visits, procedures and restrictions.

2. Group 1. Healthy adult volunteers (6 participants) as judged by the investigator based on medical history, physical examination, vital signs, laboratory tests and ECG; and is a non-smoker defined as not having smoked (inhalation of tobacco/nicotine or drugs of abuse) for four weeks prior to the study.

3. Group 2 participants with underlying lung disease as specified - smokers (4 participants see below), asthmatics (4 participants) and patients with cystic fibrosis (4 participants). These patients should have no other associated co-morbidities such as cardiovascular, renal or liver - either diagnosed or suspected through the tests listed to be performed at screening. Their underlying condition must be stable as defined by no exacerbations or significant changes in their underlying condition or treatment for the past four weeks. The participant will be advised to have the permission of their treating physician to participate in this study.

4. Group 2 participants in the smokers group must be regular smokers as defined by the
minimum pack year history (1 pack/week for 6 months) and must be able to withhold
smoking for the duration of the testing as they will be in a non-smoking environment and will not be able to leave the premises during testing. These patients should also have no other associated co-morbidities such as cardiovascular, renal or liver - either diagnosed or suspected through the tests performed at screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Under the age of 18 years. No upper age limits.

2. The COVID-19 serology or swab test performed at screening is positive.

3. Participants with a known diagnosis of Chronic Obstructive Pulmonary Disease (COPD) or who, at screening, have an FEV1/FVC reading on spirometry of less than 70% predicted which is indicative of COPD.

4. Participants in Group 2 who at screening have an FEV1 reading on spirometry of less than 40% predicted.

5. Positive hepatitis or HIV serology testing performed at screening.

6. Participant is pregnant or breast-feeding.

7. Participants known to be allergic or have reacted to alcohol in the past

8. Participants unable to be exposed to alcohol for any reason including religious or cultural reasons

9. In the opinion of the Investigator, the participant is unable to comply with the procedures required for the testing.

10. Previous history of alcohol dependence or abuse, defined as greater than 21 units per week for males and greater than 14 units per week for females. Where 1 unit equals 360 mL of beer, 150 mL wine or 45 mL of spirits.

11. No specific medications are to be avoided, although if in the opinion of the medical staff that a new medication reported prior to starting the study has the potential for an interaction with ethanol, the participant will be precluded from participating while on that medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
All participants receive the same intervention with three doses of inhaled ethanol at three different concentrations 2 hours apart.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Prior studies performed under similar conditions strongly support the expectation of positive safety and tolerability outcomes from this study with no significant adverse events anticipated. With this in mind, and in the absence of an evident direct comparator, a sample size of 18 participants and no placebo group is considered to be adequate to confirm the study aims.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/02/2021
Actual
Date of last participant enrolment
Anticipated
18/03/2021
Actual
Date of last data collection
Anticipated
26/03/2021
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 17281 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 30999 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 306503 0
Other Collaborative groups
Name [1] 306503 0
Wal-yan Centre for Respiratory Research
Country [1] 306503 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Telethon Kids Institute
Address
15 Hospital Ave, Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 307028 0
None
Name [1] 307028 0
Address [1] 307028 0
Country [1] 307028 0
Other collaborator category [1] 281430 0
Other Collaborative groups
Name [1] 281430 0
Inspiring Pty Ltd
Address [1] 281430 0
Telethon Kids Institute, 15 Hospital Ave, Nedlands WA 6009
Country [1] 281430 0
Australia
Other collaborator category [2] 281432 0
Other Collaborative groups
Name [2] 281432 0
Wal-yan Centre for Respiratory Research
Address [2] 281432 0
Telethon Kids Institute, 15 Hospital Ave, Nedlands WA 6009
Country [2] 281432 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306702 0
Bellberry
Ethics committee address [1] 306702 0
123 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 306702 0
Australia
Date submitted for ethics approval [1] 306702 0
18/08/2020
Approval date [1] 306702 0
17/11/2020
Ethics approval number [1] 306702 0
2020-08-774

Summary
Brief summary
The aim of this study is to confirm earlier studies demonstrating safety and tolerability of inhaled aerosolised ethanol in adult volunteer participants. The ethanol will be administered to the upper and lower airways using a specifically-designed closed-circuit nebuliser system which improves delivery efficiency by minimising escape of volatile ethanol vapor during nebulisation and at the same time meets WHO requirements for safety and protection of nearby personnel from environmental aerosol exposure and exhaled virus particles. Confirmation of safety and tolerability will reassure physicians that inhaled ethanol can be used to treat COVID-19 and other viral and bacterial respiratory infections.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104722 0
A/Prof Barry Clements
Address 104722 0
Telethon Kids Institute
15 Hospital Ave
Nedlands, Western Australia
6009
Country 104722 0
Australia
Phone 104722 0
+61 414930103
Fax 104722 0
Email 104722 0
[email protected]
Contact person for public queries
Name 104723 0
A/Prof Barry Clements
Address 104723 0
Telethon Kids Institute
15 Hospital Ave
Nedlands, Western Australia
6009
Country 104723 0
Australia
Phone 104723 0
+61 414930103
Fax 104723 0
Email 104723 0
[email protected]
Contact person for scientific queries
Name 104724 0
A/Prof Barry Clements
Address 104724 0
Telethon Kids Institute
15 Hospital Ave
Nedlands, Western Australia
6009
Country 104724 0
Australia
Phone 104724 0
+61 414930103
Fax 104724 0
Email 104724 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIA phase I clinical trial assessing the safety, tolerability, and pharmacokinetics of inhaled ethanol in humans as a potential treatment for respiratory tract infections2024https://doi.org/10.3389/fmed.2024.1324686
N.B. These documents automatically identified may not have been verified by the study sponsor.