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Trial registered on ANZCTR


Registration number
ACTRN12617000935336
Ethics application status
Approved
Date submitted
23/05/2017
Date registered
28/06/2017
Date last updated
6/06/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Standard versus mIninal Monitoring : Pragmatic triaL in hepatItis C Treatment
Scientific title
In adults planned to begin treatment with 12 weeks of Sofosbuvir/Ledipasvir for Genotype 1 hepatitis C virus infection, or Sofosbuvir/Daclatasvir for genotype 3 hepatitis C, does minimal monitoring lead to a similar chance of cure with reduced staff time and good patient acceptability compared to a current standard monitoring regimen?
Secondary ID [1] 292019 0
Nil
Universal Trial Number (UTN)
Trial acronym
SIMPLICITY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C infection 303408 0
Condition category
Condition code
Infection 302819 302819 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 2: Simplified Monitoring
Patients are treated exactly the same as if they were not in a trial apart from the degree of monitoring (which will be LESS than in the standard arm.
Treatment is with either 12 weeks of Sofosbuvir/Ledipasvir for Genotype 1 hepatitis C virus infection, or Sofosbuvir/Daclatasvir for genotype 3 hepatitis C.
Face to face clinic appointment at base line and prescription dispensing, week 4 phonecall and week 12 phonecall to make sure they are taking their medications and they are ok. week 24 FBC, EUC, LFTs, HCV qualitative viral load,
Week 26 Last clinic appointment conducted in person to get the results of the week 24 blood tests.
Phonecalls are perfromed by the nursing staff.
Appointments are made by the nursing staff.
(Qualatative is the pathology measurement we do we only want to know if the virus is detected or not detected at this satge, we don't want a level measured)
Intervention code [1] 298153 0
Treatment: Other
Comparator / control treatment
Arm 1: Standard Monitoring
Treatment is with either 12 weeks of Sofosbuvir/Ledipasvir for Genotype 1 hepatitis C virus infection, or Sofosbuvir/Daclatasvir for genotype 3 hepatitis C.
Patients are treated exactly the same as if they were not in a trial.
Face to face clinic appointment at base line and prescription dispensing, week 4 of treatment visit, pathology collected FBC, EUC, LFTs, HCV quantitative viral load , week 12 end of treatment visit, pathology collected, FBC, EUC, LFTs, HCV qualitative viral load and week 24 bloods only collected FBC, EUC, LFTs, HCV qualitative viral load.
Week 26 Last clinic appointment conducted in person to get the results of the week 24 blood tests.
Appointments are made by the nursing staff.
(Qualitative is the path measurement we do we only want to know if it is Detected or not detected at this satge, we don't want a level measured)
Control group
Active

Outcomes
Primary outcome [1] 302219 0
SVR 12: Sustained virological response 12 weeks after the end of treatment week 24 HCV qualitative viral load blood test.
Timepoint [1] 302219 0
The proportion of participants with a negative HCV PCR 12 weeks after the end of treatment, week 24 (at the end of the 12 week follow period where the patient hasn't received any of the treatment medication) HCV qualatative viral load blood test.
Primary outcome [2] 302220 0
Staff time: Number of hours (in quarter hour blocks) spent by doctors and or nurses from the treating viral hepatitis service in direct or indirect contact with the participant. This includes time spent on face to face clinic visits, phone calls, and emails.
This is collected in a table on a data collection form that is in each patient's file:
Week 1 - 24
Face to face visits
Phone calls/SMS
Emails
Letters
Other (specify)
Timepoint [2] 302220 0
from day 1 to day 180 (24 weeks - 12 weeks treatment and 12 week follow up period)
Secondary outcome [1] 335188 0
Patient acceptability assessed by a quantitative patient survey was designed specifically for this study, i have attached it in the documents section.
Timepoint [1] 335188 0
At the end of the 12 week treatment phase.
Secondary outcome [2] 336399 0
Patient satisfaction. This is an unknown quantity and part of the rationale for doing a pilot study. The key element of the survey used as the co-primary endpoint will be the overall satisfaction score at both 12 weeks. For each individual patient, these 2 scores (out of 10) will be averaged. This average score for each patient will then be summarised for the whole group as for the staff hours above.
Analysis will be by intention to treat – all participants will be counted in the group to which they were allocated, regardless of the actual amount of monitoring received.
Timepoint [2] 336399 0
At the end of the 12 week treatment phase.

Eligibility
Key inclusion criteria
These are patients who have tested to being positve to the Hepatitis C Virus and further genotype testing performed to decifer if they have either Genotype 1 or 3 as the treatment prescribed is different for each genotype.
Treatment naive (cirrhotic or not); treatment experienced (only if non-cirrhotic) – this refers to previous treatment with PEG/Riba but not DAAs
Planned to begin treatment with 8 or 12 weeks of Sof/Led or 12 weeks of Sof/Dac but without ribavirin
If HIV+ve, must be on a stable, non-interacting antiretroviral regimen for at least 3 months prior to randomisation AND have an undetectable HIV viral load and a CD4 count >=200 cells/microlitre.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Genotype 1 Treatment experienced cirrhotic (because need for 24 weeks treatment and/or ribavirin)
Genotype 3 cirrhotic (regardless of Rx experience) – because of the need for 24 weeks treatment
Child-Pugh class B or C cirrhotic (i.e. decompensated cirrhosis)
Any co-morbidities which, in the opinion of the investigators, needs any special monitoring beyond that in the minimal monitoring arm.
High risk of poor adherence (a subjective measure, as assessed by the investigators)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will be via the “Sealed Envelope” web-based randomisation service.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
It will be in permuted blocks of variable size and will be stratified by genotype (1 vs 3).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Note that this is a pilot study, and thus the sample size is largely based on feasibility (the number of patients we can reasonably expect to enrol within the timeframe). As pointed out in a recent JAMA editorial (JAMA. 2015; 314(15):1561-1562), such studies not only do not need to be based on sample size analyses, but should actively avoid formal hypothesis testing. Their key aim should be “road testing” measurement tools and refining assumptions in order to inform the design of a subsequent definitive trial.
It will include unplanned interactions – e.g. following up on abnormal blood test results, or dealing with concerns/enquiries/adverse events reported by participants.

The total number of minutes will be summarised for each group, as a mean if it is normally distributed and as a median if not, and the total in the 2 groups will be compared using a Student’s t test or Mann Whitney U test as appropriate.

3) Patient satisfaction. This is an unknown quantity and part of the rationale for doing a pilot study. The key element of the survey used as the co-primary endpoint will be the overall satisfaction score at both 12 weeks. For each individual patient, these 2 scores (out of 10) will be averaged. This average score for each patient will then be summarised for the whole group as for the staff hours above.
Analysis will be by intention to treat – all participants will be counted in the group to which they were allocated, regardless of the actual amount of monitoring received.

Due to the small sample size, there will only be 2 subgroup analyses:

a. Genotype (1 or 3)
b. Site (JHH, RBWH or RDH)

For the subsequent definitive RCT, the primary endpoint will be a simple non-inferiority design with a tight margin and SVR as the primary outcome. If there is truly no difference between the standard and experimental arms, then 894 patients are required to have 90% power to show that the upper limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will exclude a difference in favour of the standard group of more than 5%. Accounting for loss to follow up, this would require approximately 1000 patients. This would be achievable by including multiple sites (e.g. 10-15) over 12 months, but would require dedicated funding.





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,NT
Recruitment hospital [1] 8111 0
John Hunter Hospital - New Lambton
Recruitment hospital [2] 8112 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 16168 0
2305 - New Lambton
Recruitment postcode(s) [2] 16169 0
0810 - Tiwi

Funding & Sponsors
Funding source category [1] 296550 0
Hospital
Name [1] 296550 0
John Hunter Hospital
Address [1] 296550 0
Lookout Road,
New Lambton, NSW 2305
Country [1] 296550 0
Australia
Primary sponsor type
Hospital
Name
Royal Darwin Hospital
Address
Rocklands Drive, Tiwi, Northern Territory 0811
Country
Australia
Secondary sponsor category [1] 295509 0
None
Name [1] 295509 0
Address [1] 295509 0
Country [1] 295509 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297764 0
Hunter New England Research & Ethics Committee
Ethics committee address [1] 297764 0
Lookout Road, New Lambton, NSW 2305
Ethics committee country [1] 297764 0
Australia
Date submitted for ethics approval [1] 297764 0
17/03/2016
Approval date [1] 297764 0
04/05/2016
Ethics approval number [1] 297764 0
HREC/16/HNE/127

Summary
Brief summary
In March 2016, several new, all oral treatments became available in Australia for chronic hepatitis C virus (HCV) infection, bringing the “interferon era” to a close. These new treatments are much easier to take and more effective than the previous standard treatment, which was based on an injected medicine called interferon.

Although we know these new treatments are very safe with side effect rates in clinical trials similar to placebo (sugar pills), we don’t know exactly how much monitoring is needed during a course of treatment. A “standard” monitoring plan has recently been developed by Australian experts, but this is based on what we know of the new treatments, and it has never been directly compared with less intensive monitoring.
For the old interferon-based treatments, patients had some blood tests and a clinic appointment every 2 to 4 weeks for at least 24 weeks. For the new all-oral treatments, we know that much less intense monitoring is needed, but different monitoring strategies have not been tested in clinical trials.

The purpose of SIMPLICITY is to compare “standard monitoring” with “minimal monitoring”, to determine if minimal monitoring results in similar cure rates but with lower cost and better patient satisfaction. The SIMPLICITY trial is being co-ordinated by Associate Professor Joshua Davis, who is based at John Hunter Hospital in Newcastle, and at the Menzies School of Health Research in Darwin. It aims to enrol a total of 100 participants at two sites in Australia (Darwin and Newcastle).
There are no medications being given specifically as part of this study. You will receive the same medications whether or not you choose to take part in this study. The only difference between the two study arms is the number of blood tests and clinic visits during your course of treatment.

Trial website
Trial related presentations / publications
None
Public notes
None
Attachments [2] 1735 1735 0 0
Attachments [3] 1736 1736 0 0
Attachments [4] 1737 1737 0 0

Contacts
Principal investigator
Name 75042 0
A/Prof Joshua Davis
Address 75042 0
I & ID
Royal Newcastle centre
John Hunter Hospital
Lookout Road
New Lambton, NSW, 2305
Country 75042 0
Australia
Phone 75042 0
+61 249213000
Fax 75042 0
+61 249855978
Email 75042 0
joshua.davis@menzies.edu.au
Contact person for public queries
Name 75043 0
Ms Mel Young
Address 75043 0
Gastroenterology Department
John Hunter Hospital
Lookout Road
New Lambton, NSW, 2305
Country 75043 0
Australia
Phone 75043 0
+61 249214853
Fax 75043 0
+61 249855978
Email 75043 0
melissa.young@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 75044 0
A/Prof Joshua Davis
Address 75044 0
I & ID
Royal Newcastle centre
John Hunter Hospital
Lookout Road
New Lambton, NSW, 2305
Country 75044 0
Australia
Phone 75044 0
+61 249213000
Fax 75044 0
+61 249855978
Email 75044 0
joshua.davis@menzies.edu.au

No data has been provided for results reporting
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