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Trial registered on ANZCTR


Registration number
ACTRN12618001740280p
Ethics application status
Submitted, not yet approved
Date submitted
17/10/2018
Date registered
23/10/2018
Date last updated
23/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Adverse reactions to Hepatitis C drugs
Scientific title
Drug hypersensitivity reactions to direct acting hepatitis C virus antiviral drugs
Secondary ID [1] 296361 0
Nil known
Universal Trial Number (UTN)
U1111-1222-5058
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypersensitivity reaction to direct acting antiviral drugs used to treat Hepatitis C 310091 0
Condition category
Condition code
Inflammatory and Immune System 308836 308836 0 0
Allergies

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
2
Target follow-up type
Years
Description of intervention(s) / exposure
The aim of this project is to investigate the underlying genetic mechanism of cases of adverse reactions to direct acting antiviral drugs used to treat Hepatitis C. People on the study will be asked to supply buccal tissue samples (DNA) so that whole genomic analysis will identify potential genetic associations. This may help predict which people are sensitive to these antiviral drugs and therefore prevent severe reactions. Those people with demonstrated hypersensitivity reactions to direct acting antiviral medication will be compared to people treated with direct acting antiviral drugs that have not had a reaction. After the initial recruitment and enrolment visit, there will be no follow up - information obtained will be included in a National drug allergy registry.
Intervention code [1] 312691 0
Early Detection / Screening
Comparator / control treatment
Those people with demonstrated hypersensitivity reactions to direct acting antiviral medication will be compared to people treated with direct acting antiviral drugs that have not had a reaction.
People identified (by participating hepatologists, clinical immunologists, hospital medical staff) as potentially having HCV treated with direct acting antiviral medications and having a hypersensitivity reaction will be invited to take part in this research study. A similar group of gender and age matched controls (people that have been treated for hepatitis C with direct acting antiviral medications that have not had a hypersensitivity reaction) will be recruited for comparison purposes. The diagnosis of drug hypersensitivity reaction will be verified or dismissed. Those participants that have been treated with direct acting antiviral medications without a verified hypersensitivity reaction will be recruited into the Control group. Recruitment for both groups will be simultaneous and will commence once ethics approval has been granted. Medical records at both Sir Charles Gairdner Hospital (WA) and St Vincent's Hospital (Vic) will be used to identify potential participants.
Control group
Active

Outcomes
Primary outcome [1] 307808 0
HLA allele as assessed by whole genome sequencing of DNA from buccal swab
Timepoint [1] 307808 0
At recruitment, after signed consent
Secondary outcome [1] 353000 0
Severity of hypersensitivity reaction as assessed by data-linkage to medical records
Timepoint [1] 353000 0
Two years after first participant recruited

Eligibility
Key inclusion criteria
Diagnosis of drug hypersensitivity reaction (HSR) confirmed using:
• Modified European Network of Drug Allergy (ENDA) drug allergy questionnaire.
• Severe Cutaneous Adverse Reactions (SCAR) to drugs criteria.
• Idiosyncratic drug-induced liver injury (iDILI) criteria.
• Clinical severity.
• Direct acting antiviral drug treatment at time of hypersensitivity reaction.
• Laboratory parameters: liver function test, total bilirubin.
• Informed consent for health information acquisition, DNA bio-sample (buccal swab).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• People under the age of 18years.
• Females that are pregnant.
• Those people not willing to give consent.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
SAMPLE SIZE
It is anticipated that 6 patients can be recruited each month, over an 18month period. Therefore, we aim to recruit 108 patients that have an hypersensitivity reaction to a direct acting antiviral medication; each of these patients will have an age and gender matched control patient who did not have a hypersensitivity reaction to a direct acting antiviral medication. We expect this to provide enough information based on similar research to identify genetic differences between the groups.
Statistical analysis
Patient variables, such as age, sex, co-infection history and clinical laboratory parameters (e.g. liver function tests, full blood count, inflammatory markers, biopsy material) will be summarised. Categorical patient variables will be compared between hypersensitivity reaction and control groups using McNemar’s tests, whilst continuous patient variables will be compared between groups using paired t-tests.
The proportion of patients with each HLA allele will be summarised and compared between hypersensitivity reaction and control groups using McNemar’s tests (performed separately for each HLA allele). P-values will be adjusted using the false discovery rate to take into account the multiple comparisons.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 12195 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 12196 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 24366 0
6009 - Nedlands
Recruitment postcode(s) [2] 24367 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 300963 0
Government body
Name [1] 300963 0
Australian Centre for HIV and Hepatitis Virology Research
Address [1] 300963 0
176 Hawkesbury Rd, Westmead NSW 2145
Country [1] 300963 0
Australia
Primary sponsor type
Individual
Name
Prof Michaela Lucas
Address
The Harry Perkins Institute of Medical Research
6 Verdun St, Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 300541 0
None
Name [1] 300541 0
Address [1] 300541 0
Country [1] 300541 0
Other collaborator category [1] 280394 0
Individual
Name [1] 280394 0
Prof Alex Thompson
Address [1] 280394 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country [1] 280394 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 301727 0
Sir Charles Gairdner Osborne Park Health Care Group Human Research Ethics Committee
Ethics committee address [1] 301727 0
Sir Charles Gairdner Hospital
Level 2, A Block
Hospital Avenue
NEDLANDS WA 6009
Ethics committee country [1] 301727 0
Australia
Date submitted for ethics approval [1] 301727 0
08/08/2018
Approval date [1] 301727 0
Ethics approval number [1] 301727 0

Summary
Brief summary
Adverse reactions to direct acting antiviral medications to treat hepatitis C have occurred in some people. These adverse reactions include damage to the liver. The aim of this project is to study the genetic association of these cases of adverse reactions. People that have had direct acting antiviral medications to treat hepatitis C and have had a hypersensitivity reaction will be compared to those that have had direct acting antiviral medications to treat hepatitis C and have not had a hypersensitivity reaction. The study will require people to supply buccal tissue samples so that identification of potential genetic association can be established through DNA testing. This may help predict which people are sensitive to these antiviral drugs and therefore prevent sever reactions. These DNA samples will be destroyed after the genetic testing has been completed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87906 0
Prof Michaela Lucas
Address 87906 0
The Harry Perkins Institute of Medical Research
6 Verdun St
Nedlands WA 6008
Country 87906 0
Australia
Phone 87906 0
+61 (08) 6151 0700
Fax 87906 0
Email 87906 0
Michaela.Lucas@health.wa.gov.au
Contact person for public queries
Name 87907 0
Prof Michaela Lucas
Address 87907 0
The Harry Perkins Institute of Medical Research
6 Verdun St
Nedlands WA 6008
Country 87907 0
Australia
Phone 87907 0
+61 (08) 6151 0700
Fax 87907 0
Email 87907 0
Michaela.Lucas@health.wa.gov.au
Contact person for scientific queries
Name 87908 0
Prof Michaela Lucas
Address 87908 0
The Harry Perkins Institute of Medical Research
6 Verdun St
Nedlands WA 6008
Country 87908 0
Australia
Phone 87908 0
+61 (08) 6151 0700
Fax 87908 0
Email 87908 0
Michaela.Lucas@health.wa.gov.au

No data has been provided for results reporting
Summary results
Not applicable