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Trial registered on ANZCTR


Registration number
ACTRN12615001111561
Ethics application status
Approved
Date submitted
13/08/2015
Date registered
21/10/2015
Date last updated
21/10/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparison of the degree and speed of virologic response to two treatment options in patients with chronic Hepatitis C.
Scientific title
Chronic hepatitis C virus genotype 4 infected patients treated with a either one of generic Sofosbuvir plus ribavirin for 3 months versus 6 months duration based on their very rapid or ultra rapid virologic response
Secondary ID [1] 287269 0
None
Universal Trial Number (UTN)
None
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic hepatitis C 295889 0
Condition category
Condition code
Oral and Gastrointestinal 296140 296140 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 296141 296141 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1 started treatment with Gratisovir 400mg tablets (Sofosbuvir-Pharco), one tablet daily after main meal plus Weight-Based Dosing (WBD) of Hepaverin capsules (Ribavirin) 1200mg if body weight is 75kg or above and 1000 mg if body weight is <75 kg, twice daily, orally; patients who achieve very rapid Virologic response (i.e. undetectable hepatitis C virus RNA Levels at week 2) will be then randomized to receive treatment for a total duration of 3 months or 6 months. Patients who do not achieve the very rapid virologic response will be treated for a total duration of 6 months.
Intervention code [1] 292568 0
Treatment: Drugs
Comparator / control treatment
Group 2 started treatment with Grateziano 400mg tablets (Sofosbuvir-EEPI), one tablet daily after main meal plus Weight-Based Dosing (WBD) of Hepaverin capsules (Ribavirin) 1200mg if body weight is 75kg or above and 1000 mg if body weight is below 75 kg, twice daily, orally; for a duration of 6 or 3 months according to further randomization for those achieving vRVR.
Control group
Active

Outcomes
Primary outcome [1] 295817 0
Sustained virologic response (serum HCV RNA below level of quantification at 12 weeks post treatment).
Timepoint [1] 295817 0
12 weeks after end of treatment
Primary outcome [2] 295818 0
very Rapid Virologic Response (vRVR) (i.e. Serum HCV RNA below level of quantification at the end of week 2 of therapy)
Timepoint [2] 295818 0
2 weeks after starting treatment
Primary outcome [3] 295819 0
ultra Rapid Virologic Response (i.e. serum HCV RNA below level of quantification or decreased by at least 4 Logs10 at the end of one week of therapy)
Timepoint [3] 295819 0
1 week after treatment start
Secondary outcome [1] 316595 0
Adverse drug reactions assessed clinically or by laboratory tests; examples of possible adverse reactions/events are: anemia, thrombocytopenia (assessed by complete blood count), headache, fatigue, abdominal pain, skin rash, itching (assessed clinically by symptoms and signs)
Timepoint [1] 316595 0
throughout the study, by weekly clinical evaluation, complete blood count, liver and function tests.

Eligibility
Key inclusion criteria
Chronic Hepatitis C genotype 4 infection with HCV RNA levels > 4 Log 10
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Other causes of chronic hepatitis such as hepatitis B or autoimmune hepatitis.
critically ill patients and severe organ dysfunctions

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)
The study is a randomized, open-label, comparative effectiveness study design.
Consecutive patients presenting to the outpatient clinics with chronic HCV were screened for eligibility. Those eligible were randomized centrally to 2 groups.
Allocation was carried out with the randomization centrally by patient sequent numbers and the allocation sequence kept in sealed opaque envelopes to be opened by investigators at day 0 just before starting treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization was done using software generated balanced block randomization technique.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Those who experienced vRVR were further randomized to either 3 months treatment duration or 6 months duration
Phase
Phase 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/06/2015
Actual
9/06/2015
Date of last participant enrolment
Anticipated
15/12/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment outside Australia
Country [1] 7089 0
Egypt
State/province [1] 7089 0
Alexandria

Funding & Sponsors
Funding source category [1] 291826 0
Charities/Societies/Foundations
Name [1] 291826 0
Abass Helmy Charity establishment
Country [1] 291826 0
Egypt
Primary sponsor type
Individual
Name
Mostafa Yakoot
Address
Green Clinic and Research Centre
27 Green Street, Alexandria, Egypt, 21121
Country
Egypt
Secondary sponsor category [1] 290489 0
None
Name [1] 290489 0
None
Address [1] 290489 0
Country [1] 290489 0
Other collaborator category [1] 278579 0
None
Name [1] 278579 0
None
Address [1] 278579 0
None
Country [1] 278579 0
Egypt

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293345 0
GREEN CRC Ethics committee #1
Ethics committee address [1] 293345 0
27 Green Street, Alexandria 21121
Ethics committee country [1] 293345 0
Egypt
Date submitted for ethics approval [1] 293345 0
Approval date [1] 293345 0
12/05/2015
Ethics approval number [1] 293345 0

Summary
Brief summary
We designed this comparative effectiveness study as a quick economic model to timely support making an urgent choice for a cost/effective dual antiviral treatment protocol for chronic hepatitis C in a limited resource charity setting.
Methods: Data collected during the period of this interim report from the first 25 patients randomized to either one of two generic Sofosbuvir products (Grateziano or Gratisovir) in a daily dose of one 400 mg tablet plus a weight based ribavirin dose, were analyzed for both the degree and speed of virus load reduction at the end of 1 and 2 weeks from starting treatment.
Results:
As we planned to include a sample of 200 patients for a mean follow up duration of 9 months, the full report is expected to be available by the end of the year 2016.
Here we present interim data collected from the first 25 patients included in the study during the first 2 weeks of treatment.

The Log10 transformed virus load (Log PCR) in both groups showed an almost equal markedly significant reduction both at the end of week 1 and week 2 of starting treatment by more than 4 and 5 Logs respectively. The differences between the 2 treatment groups at both analysis points were not statistically significant (p = 602, 728) by both student t test and repeated measures ANOVA test.Whereas the difference between proportions of patients with ultra-rapid virologic response (uRVR) at the end of week 1 and very-rapid virologic response (vRVR) at the end of week 2 in both groups were also not statistically significant (vRVR: 10/13 versus 10/12 respectively (p = 0.95, 0.86 respectively))
Conclusion: We can conclude from this interim report that the two generic products Gratisovir and Grateziano are almost equally effective and equally rapid in reducing the HCV virus load. The predictive accuracy of our suggested markers of efficacy (the vRVR and the uRVR) and the results of truncated 3 months response guided therapy versus the recommended 6 months course duration will be addressed upon full completion of the study in our final report.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59494 0
Dr Mostafa Yakoot
Address 59494 0
Green Clinic and Research Centre
27 Green Street, Alexandria city, post code 21121
Country 59494 0
Egypt
Phone 59494 0
+201223927561
Fax 59494 0
Email 59494 0
[email protected]
Contact person for public queries
Name 59495 0
Mostafa Yakoot
Address 59495 0
Green Clinic and Research Centre
27 Green Street, Alexandria city, post code 21121
Country 59495 0
Egypt
Phone 59495 0
+201223927561
Fax 59495 0
Email 59495 0
[email protected]
Contact person for scientific queries
Name 59496 0
Mostafa Yakoot
Address 59496 0
Green Clinic and Research Centre
27 Green Street, Alexandria city, post code 21121
Country 59496 0
Egypt
Phone 59496 0
+201223927561
Fax 59496 0
Email 59496 0
[email protected]

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