Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001535864
Ethics application status
Approved
Date submitted
20/10/2021
Date registered
10/11/2021
Date last updated
16/06/2023
Date data sharing statement initially provided
10/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Ivermectin to prevent Coronavirus
Scientific title
A pilot randomized placebo-controlled double-blind trial of single dose oral Ivermectin for post-exposure prophylaxis of SARS-CoV-2
Secondary ID [1] 305168 0
EP-Ivermectin-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 323436 0
SARS-CoV-2 324193 0
Condition category
Condition code
Infection 320989 320989 0 0
Other infectious diseases
Respiratory 321585 321585 0 0
Other respiratory disorders / diseases
Public Health 321586 321586 0 0
Epidemiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose of ivermectin 200ug/kg orally or matching placebo tablets. The trial will recruit participants who have, in the preceding 72 hours, had close contact with a person infectious with SARS-CoV-2. Participants must have, since that contact, tested negative for SARS-CoV-2 on a polymerase chain reaction (PCR) from a pharyngeal swab or on a rapid antigen test (RAT) and be asymptomatic of: fever, new cough, sore throat, rhinorrhoea, loss of smell, loss of taste, or more difficulty breathing than usual. The baseline PCR or RAT is required to determine qualification for the study but is not performed as part of the study.
Participants will be randomized 1:1 to receive either Ivermectin 200ug/kg orally or Placebo tablets on Day 1. Approximately 4 hours after receipt of the study drug the participants will be contacted by staff from the CRO and asked whether all study tablets were taken and, if not, why not.
The trial will recruit until 40 participants have converted to a positive pharyngeal swab PCR or positive TGA-approved RAT for SARS-CoV-2 within 14 days of their contact with an infectious SARS-CoV-2 index case.
Intervention code [1] 321569 0
Prevention
Intervention code [2] 322040 0
Treatment: Drugs
Comparator / control treatment
Participants will be randomised 1:1 ivermection to placebo. Commercial placebo tablets will be provided by Edenbridge Pharmaceuticals in the USA.
Control group
Placebo

Outcomes
Primary outcome [1] 328766 0
Amongst the 40 participants who convert to a positive PCR or or positive TGA-approved RAT for SARS-CoV-2, the proportion who received Ivermectin. To determine this, participants will be asked whether they took some/all of the study drug (for sensitivity analyses), Their information will be entered into the study database (REDCap) which will also contain their treatment allocation (only the study Pharmacists are unblinded to this information prior to database lock).
Timepoint [1] 328766 0
14 days after initial COVID-19 close contact
Secondary outcome [1] 400267 0
Amongst the 40 participants who convert to a positive PCR or positive TGA-approved RAT for SARS-CoV-2,
the difference (those who received Ivermectin versus those who received placebo) in days alive free of SARS-CoV-2 symptoms (fever, new cough, sore throat, rhinorrhoea, loss of smell, loss of taste, more difficulty breathing than usual) at Day 14. Participants will be followed up with phone calls weekly for 1 month and then monthly until 6 months post randomisation. Details of any follow up PCR or RAT test results since the previous study contact will be entered in the database. For the first 4 weeks participants also complete a Symptom Questionnaire for fever, new cough, sore throat, rhinorrhoea, loss of smell, loss of taste, more difficulty breathing than usual.
Timepoint [1] 400267 0
Day 14 post treatment. Follow up calls weekly for 1 month.
Secondary outcome [2] 400268 0
Amongst the 40 participants who convert to a positive PCR or positive TGA-approved RAT for SARS-CoV-2, the difference (those who received Ivermectin versus those who received placebo) in days alive free of SARS-CoV-2 symptoms (fever, new cough, sore throat, rhinorrhoea, loss of smell, loss of taste, more difficulty breathing than usual) at Day 28. Details of any follow up PCR or RAT results since the previous study contact will be entered in the database. For the first 4 weeks participants also complete a Symptom Questionnaire for fever, new cough, sore throat, rhinorrhoea, loss of smell, loss of taste, more difficulty breathing than usual.
Timepoint [2] 400268 0
Day 28 post treatment. Follow up calls weekly for 1 month..
Secondary outcome [3] 400269 0
Amongst the 40 participants who convert to a positive PCR or positive TGA-approved RAT for SARS-CoV-2, the difference (those who received Ivermectin versus those who received placebo) in days alive free of presentation to hospital and/or acute hospital care and/or to outpatient care under hospital supervision at Day 28. Acute hospital care will not include days spent in an acute hospital ward solely because a rehabilitation or non-acute care facility bed was not available. During the weekly follow up calls, participants will be asked about any presentation to hospital and/or acute hospital care and/or to outpatient care under hospital supervision. If applicable, then the relevant hospital will be contacted to obtain further details regarding the admission.
Timepoint [3] 400269 0
Day 28 post treatment. Follow up calls weekly for 1 month.
Secondary outcome [4] 400270 0
Amongst the 40 participants who convert to a positive PCR or positive TGA-approved RAT for SARS-CoV-2, the difference (those who received Ivermectin versus those who received placebo) in time from exposure to an index case of SARS-CoV-2 to a positive PCR or positive TGA-approved RAT for SARS-CoV-2. Time of exposure to an index case of SARS-CoV-2 (documented in REDCap at time of baseline collection), treatment allocation (documented in REDCap) and conversion to a positive PCR or positive TGA-approved RAT post treatment (documented in PCR result sent to participant, or RAT, and forwarded to CRO) will be captured in the study database.
Timepoint [4] 400270 0
Day 14 post treatment

Eligibility
Key inclusion criteria
1. In the preceding 72 hours, had close contact with a person infectious with SARS-CoV-2.
• AND that contact was in the context of i) a participant’s home or ii) an indoor work environment or iii) a family gathering or a social or a religious function or a ceremony each being of less than 30 people.
• AND since that contact, tested negative for SARS-CoV-2 on polymerase chain reaction(PCR) of pharyngeal swab or on a rapid antigen test (RAT).
• AND are asymptomatic of fever, new cough, sore throat, rhinorrhoea, loss of smell, loss of taste, or more difficulty breathing than usual.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Not agreeable to being at home for delivery of the investigational product
•The close contact with an infectious index case of SARS-CoV-2 occurred in a hospital
•Residing outside the current geographic recruitment area
•The index case who has SARS-CoV-2 lives in the same residence as the potential participant.
•Another person who lives in the same residence as the potential participant has returned a positive pharyngeal PCR or a RAT for SARS-CoV-2 in the last 2 weeks.
•Unable to provide the name, address and phone number of the potential participant’s general practitioner/primary care physician OR does not have such a general practitioner/primary care physician.
. Has not attended a doctor at the practice of the above general practitioner/primary care physician for more than 12 months. (NB Given the pandemic, that attendance may have been by telehealth).
• Lives alone (as potentially at higher risk should there be a serious adverse event).
• Unable to provide the name and phone number of a back-up contact person.
• History of past infection with SARS-CoV-2.
• Use of Ivermectin for any purpose in 5 weeks prior to enrolment.
• Known past allergy or severe adverse reaction to Ivermectin.
• Weight <45kg or > 120kg.
• Pregnant or breast feeding.
• Not willing to refrain from falling pregnant or fathering a child for 6 months after last dose of investigational product.
• Cirrhosis or known decompensated liver disease (Child-Pugh B or C).
• Current use, or use within the last 3 months, of the drug amiodarone.
• Current use of any of the following drugs: warfarin, verapamil, diltiazem, quinidine, spironolactone, ciclosporin, tacrolimus, cobicistat, indinavir, ritonavir, didanosine (DDI), ketoconazole, itraconazole, fusidic acid, erythromycin, clarithromycin.
• Past sedation or somnolence from products containing codeine
• History of residency or travel to loa loa endemic areas (“Angola, Cameroon, Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial, Guinea, Gabon, Republic of Congo, Nigeria and Sudan”, Chaccour et al 2020b).
• Severe Asthma
• Encephalopathy.
. Head injury requiring medical attention in the last 6 months.
. Concussion within the last 6 months.
• Fit, seizure, stroke, TIA (transient ischaemic attack) or transient global amnesia in the last 6 months.
• History of epilepsy (as Stromectol product information notes in “Post-marketing Experience” “very rarely,…seizures”).
• Dementia of any type.
• Not usually fully independent in activities of daily living and self-care, including: washing, toileting, dressing and dental care.
• Inability of participant to communicate to the level necessary to provide verbal or written consent.
• Incarcerated by local, state or federal authorities.
• Conditions which in the opinion of the investigative team would make successful trial completion (including follow up data collection) unlikely, for example including uncontrolled substance use, poorly controlled mental state disorder.
• Unable to advise trial staff of Coronavirus vaccination status including date of administration of last vaccine dose.
. Already enrolled in another Coronavirus RCT
• In Australia, lack of a valid Medicare Card
• Unable or unwilling to have a RAT upon receipt of investigational product and on days 1, 2, 3, 4, 5, and on days 6 and 14 following close contact.
• Unable or unwilling to have a pharyngeal swab PCR test for SARS-CoV-2 at 6 and/or 14 days post initial exposure to a close contact if such tests are then practical and available given the then public health circumstances.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Pharmacist randomises using the trial database randomisation module,
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Concealed permuted blocks.
Stratified by Coronavirus vaccination status and site of exposure to index case.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The trial has over 90% power to detect (2-sided testing with an alpha of 0.05) a 66% reduction (Ivermectin versus Placebo) of the incidence of a positive pharyngeal swab PCR or a positive RAT for SARS-CoV- 2 at or before day 14 after close contact with an index case of SARS-CoV-2.
For the primary endpoint, if 200ug/kg oral Ivermectin has no benefit for post-exposure prophylaxis within 72 hours of close contact with an infectious index case of SARS-CoV-2, then, one would expect; that of the 40 participants who convert to a positive pharyngeal swab PCR or positive RAT for SARS-CoV-2, approximately half will have received Ivermectin and approximately half will have received placebo.
The proportion of those 40 participants who convert to a positive pharyngeal swab PCR or positive RAT for SARS-CoV-2, who received Ivermectin, will thus be tested as being different from a proportion of 0.5.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
22/02/2022
Actual
3/03/2022
Date of last participant enrolment
Anticipated
30/09/2023
Actual
Date of last data collection
Anticipated
31/03/2024
Actual
Sample size
Target
1000
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC

Funding & Sponsors
Funding source category [1] 309556 0
Charities/Societies/Foundations
Name [1] 309556 0
The Leona M and Harry B Helmsley Charitable Trust
Country [1] 309556 0
United States of America
Primary sponsor type
University
Name
Monash University
Address
Wellington Road, Clayton, Vic 3800
Country
Australia
Secondary sponsor category [1] 311009 0
None
Name [1] 311009 0
Address [1] 311009 0
Country [1] 311009 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309336 0
Bellberry HREC
Ethics committee address [1] 309336 0
123 Glen Osmond Road, Eastwood, SA 5063
Ethics committee country [1] 309336 0
Australia
Date submitted for ethics approval [1] 309336 0
20/10/2021
Approval date [1] 309336 0
14/12/2021
Ethics approval number [1] 309336 0
2021-09-1083

Summary
Brief summary
The trial will recruit participants who have, in the preceding 72 hours, had close contact with a person infectious with SARS-CoV-2. Participants must have, since that contact, tested negative for SARS-CoV-2 on polymerase chain reaction (PCR) of pharyngeal swab or on a rapid antigen test (RAT) and be asymptomatic of: fever, new cough, sore throat, rhinorrhoea, loss of smell, loss of taste, or more difficulty breathing than usual.
Participants will be randomized 1:1 to receive either Ivermectin 200ug/kg orally or Placebo on Day 1.
The trial will recruit until 40 participants have converted to a positive PCR or TGA-approved RAT for SARS-CoV-2 within 14 days of their contact with an infectious SARS-CoV-2 index case. Amongst the 40 participants who convert to a positive PCR or positive TGA-approved RAT for SARS-CoV-2, the proportion who received Ivermectin. Specifically, the trial will test whether that proportion is less than half.
Trial website
Trial related presentations / publications
Public notes
The Trial Principal Investigators are:
Dr Mark Stein: Melbourne, Australia
Kylie Wagstaff, PhD: Melbourne, Australia
Professor David Jans: Melbourne, Australia
Dr Jean-Jacques Rajter: Fort Lauderdale, USA
Dr Juliana Cepelowicz-Rajter: Fort Lauderdale, USA

Contacts
Principal investigator
Name 113810 0
Dr Kylie Wagstaff
Address 113810 0
Monash University
Wellington Road
Clayton, Vic 3800
Country 113810 0
Australia
Phone 113810 0
+61 3 99029348
Fax 113810 0
Email 113810 0
[email protected]
Contact person for public queries
Name 113811 0
Ms Michele Sallaberger
Address 113811 0
Neuroscience Trials Australia
30 Royal Parade, Parkville VIC 3052
Country 113811 0
Australia
Phone 113811 0
+61400935448
Fax 113811 0
Email 113811 0
[email protected]
Contact person for scientific queries
Name 113812 0
Dr Kylie Wagstaff
Address 113812 0
Monash University
Wellington Road
Clayton, Vic 3800
Country 113812 0
Australia
Phone 113812 0
+61 3 99029348
Fax 113812 0
Email 113812 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
No additional documents have been identified.