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Trial registered on ANZCTR


Registration number
ACTRN12615001167550
Ethics application status
Approved
Date submitted
3/09/2015
Date registered
2/11/2015
Date last updated
5/01/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
CHESS - Curing Hepatitis C: Effect on the Endothelium and cardiovaScular riSk - a pilot single arm trial, assessing the effect of hepatitis C virus (HCV) treatment with 12 weeks of paritaprevir/ritonavir/ombitasvir, dasabuvir +/- ribavirin on endothelial function.
Scientific title
In adults with chronic hepatitis C infection, does treating the HCV infection with 12 weeks of a direct acting antiviral combination ("Vikera Pak") result in an improvement of endothelial function as measured by reactive hyperaemia peripheral arterial tonometry?
Secondary ID [1] 287411 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CHESS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C virus infection 296116 0
Endothelial function 296117 0
Condition category
Condition code
Infection 296376 296376 0 0
Other infectious diseases
Cardiovascular 296378 296378 0 0
Diseases of the vasculature and circulation including the lymphatic system
Oral and Gastrointestinal 296460 296460 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Before and after study. All patients will be assessed at baseline, week 2 and week 4 on no HCV treatment. They will then receive 12 weeks of active treatment with the “Abbvie 3D regimen” which is as follows: paritaprevir/ritonavir/ombitasvir (150/100/25 mg once daily by mouth), dasabuvir (250 mg twice daily by mouth) and weight-based RBV dosed twice daily by mouth(1000 mg daily if body weight < 75 kg, 1200 mg daily if body weight >= 75 kg). Ribavirin will be given to GT1a patients but not to GT1b patients
Intervention code [1] 292763 0
Treatment: Drugs
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296023 0
Change in RH-PAT index over 12 weeks of HCV treatment compared with a 4 week baseline period
Timepoint [1] 296023 0
3 baseline time points (Week 0, 2 and 4), 4 time points whilst receiving HCV treatment (study weeks 5, 6, 8, 16, which is treatment weeks 1,2,4 and 12)
Secondary outcome [1] 317274 0
1. Change in endothelial function, (assessed by RHPAT index) from baseline to 12 weeks post treatment compared with the pre-treatment period.
Timepoint [1] 317274 0
3 baseline time points (Week 0, 2 and 4), and 1 follow up time point (study week 28, which is 12 weeks after the end of the treatment course).
Secondary outcome [2] 317453 0
2. Change in serum Angiopoietin 2 ( a marker of endothelial cell activation) over 12 weeks of HCV treatment compared with a 4 week baseline period

Timepoint [2] 317453 0
3 baseline time points (Week 0, 2 and 4), 4 time points whilst receiving HCV treatment (study weeks 5, 6, 8, 16, which is treatment weeks 1,2,4 and 12)
Secondary outcome [3] 317454 0
Change in serum concentrations of proinflammatory cytokines (IL6, INF gamma and TNF alpha) over 12 weeks of HCV treatment compared with a 4 week baseline period
Timepoint [3] 317454 0
3 baseline time points (Week 0, 2 and 4), 4 time points whilst receiving HCV treatment (study weeks 5, 6, 8, 16, which is treatment weeks 1,2,4 and 12)
Secondary outcome [4] 317455 0
Correlation between change in plasma HCV viral load over time and change in endothelial function (assessed by RHPAT index).
Timepoint [4] 317455 0
3 baseline time points (Week 0, 2 and 4), 4 time points whilst receiving HCV treatment (study weeks 5, 6, 8, 16, which is treatment weeks 1,2,4 and 12)
Secondary outcome [5] 317456 0
Correlation between change in plasma HCV viral load over time and change in endothelial cell activation (assessed by plasma Angiopoietin 2 concentration).
Timepoint [5] 317456 0
3 baseline time points (Week 0, 2 and 4), 4 time points whilst receiving HCV treatment (study weeks 5, 6, 8, 16, which is treatment weeks 1,2,4 and 12)

Eligibility
Key inclusion criteria
1. Age >= 18 years
2. Chronic HCV infection (HCV PCR positive for at least 6 months)
3. HCV Genotype 1a or 1b
4. HCV viral load at screening of >=10,000 IU/ml
5. Absence of advanced fibrosis as defined by fibroscan within 12months prior to randomisation of < 9.6 kPa
6. Females who are potentially fertile must agree to use 2 forms of reliable contraception
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cirrhosis as defined by any one of
a. Fibroscan in past 12 months >=12kPa
b. Liver biopsy in past 5 years showing F4 fibrosis
c. Clinical or radiological evidence of portal hypertension (any of varices, splenomegaly, reversal of flow in portal vein, ascites, encephalopathy)
2. Receiving prescribed medication which has a significant interaction with the AbbVie 3D+R regimen which cannot be ceased or substituted
3. Previous treatment with HCV protease-inhibitor based therapy. (Previous treatment with interferon +/- ribavirin, including both relapsers and null responders is allowed).
4. Screening laboratory values showing any of:
a. ALT or AST > 10x ULN
b. eGFR <60ml/min
c. Albumin <=30 g/dL
d. INR >1.3
e. Haemaglobin <110 g/dL
f. Platelet count<140 cells/mm3
g. Total serum bilirubin >2 x ULN
5. Known latex allergy
6. Receiving nitrates that cannot be ceased (isosorbide mononitrate, GTN patch)

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)
Open label before and after study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
N/A
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome measure is the change in RH-PAT index between weeks 0 and 12 of treatment compared with during the pre-treatment observational phase. The two periods will be compared using a mixed effects linear regression model, with the slope and intercept of the model-fitted RHPAT trend line from the treatment period compared with that from the baseline period.

Recruitment
Recruitment status
Completed
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)
NSW
Recruitment hospital [1] 4299 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment postcode(s) [1] 10236 0
2299 - Lambton

Funding & Sponsors
Funding source category [1] 291977 0
Commercial sector/Industry
Name [1] 291977 0
Abbvie Sciences
Address [1] 291977 0
AbbVie Pty Ltd
Gateway 241, Level 7,
241 O’Riordan Street,
MASCOT, NSW 2020
Country [1] 291977 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Lookout Road
New Lambton Heights
NSW 2299
Country
Australia
Secondary sponsor category [1] 290642 0
University
Name [1] 290642 0
Hunter Medical Research Institute
Address [1] 290642 0
Lookout Road
New Lambton Heights
NSW 2299
Country [1] 290642 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293470 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 293470 0
Lookout Road
New Lambton Heights
NSW 2299
Ethics committee country [1] 293470 0
Australia
Date submitted for ethics approval [1] 293470 0
03/04/2015
Approval date [1] 293470 0
03/04/2015
Ethics approval number [1] 293470 0
15/04/15/3.01

Summary
Brief summary
Hepatitis C virus (HCV) leads to cirrhosis and/or hepatocellular carcinoma in 20-40% of those infected after 30 years. It is unclear whether the remaining 60-80% of those with HCV derive an objective physical health benefit from the treatment and cure of HCV infection. HCV infection appears to be associated with increased cardiovascular risk, however this is controversial, and it is unclear whether the mechanism is through HCV-induced metabolic syndrome and diabetes, or through chronic inflammation and endothelial dysfunction. The aim of this study if to determine feasibility of using RH-PAT to measure change in endothelial function over time during HCV treatment, to refine assumptions and to seek a signal of effect. These data will then be used to determine if a larger multicentre trial is justifiable and to inform its design.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 60058 0
Dr Joshua Davis
Address 60058 0
C/- Department of Immunology and Infectious Diseases
John Hunter Hospital
Lookout Road
New Lambton Heights
NSW 2299
Country 60058 0
Australia
Phone 60058 0
+61 249 213000
Fax 60058 0
Email 60058 0
Joshua.Davis@hnehealth.nsw.gov.au
Contact person for public queries
Name 60059 0
Dr Joshua Davis
Address 60059 0
C/- Department of Immunology and Infectious Diseases
John Hunter Hospital
Lookout Road
New Lambton Heights
NSW 2299
Country 60059 0
Australia
Phone 60059 0
+61 249 213000
Fax 60059 0
Email 60059 0
Joshua.Davis@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 60060 0
Dr Joshua Davis
Address 60060 0
C/- Department of Immunology and Infectious Diseases
John Hunter Hospital
Lookout Road
New Lambton Heights
NSW 2299
Country 60060 0
Australia
Phone 60060 0
+61 249 213000
Fax 60060 0
Email 60060 0
Joshua.Davis@hnehealth.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary