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Trial registered on ANZCTR


Registration number
ACTRN12617000263392
Ethics application status
Approved
Date submitted
18/12/2016
Date registered
20/02/2017
Date last updated
10/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Fixed twelve weeks duration versus response tailored course of dual Sofosbuvir/Daclatasvir therapy in Egyptian adult and adolescent patients with chronic hepatitis C infection (HCV).
Scientific title
Fixed twelve weeks duration versus response tailored course of dual Sofosbuvir/Daclatasvir therapy in Egyptian adult and adolescent patients with chronic hepatitis C infection (HCV).
prospective, randomized, open-label, non-inferiority, multi-center study
Secondary ID [1] 290768 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic virus hepatitis C infection 301366 0
Condition category
Condition code
Infection 301119 301119 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Response guided duration of therapy:
Dual treatment with weight based Gratisovir (Sofosbuvir) + weight based Daclatasvir for doses according to the following table:
* Gratisovir (Sofosbuvir) 400mg / 200 mg tablets on daily doses based on body weight (20 – 29.9 Kg will take one 200 mg tablet daily); (30 – 39.9 Kg will take 1.5 tablets daily); (> 40 Kg/adults will take 2 tablets (or 1 table of 400 mg) once daily)
* + Daclatasvir 60 mg/30 mg tablets on daily doses based on body weight or according to the following schedule:
(20 – 30 Kg: will take 30 mg once daily),
(31 – 45 Kg: 45 mg once daily)
(> 45 Kg/adults: 60 mg once daily)

And for a duration tailored according to the very rapid virological response (vRVR) for each patient::
* Those who will show very show rapid virological response (undetectable HCV RNA at week 2) will be treated with 8 weeks duration.

* Rest will complete the 12 weeks duration.

Adherence to the study protocol and medications will be monitored at each visit by counting the number of pills (if any) remained in the medication packets.
Intervention code [1] 296677 0
Treatment: Drugs
Comparator / control treatment
Fixed 12 weeks duration of dual treatment:
• Dual treatment with weight based Gratisovir (Sofosbuvir) + weight based Daclatasvir for doses according to the following table:
* Gratisovir (Sofosbuvir) 400mg / 200 mg tablets on daily doses based on body weight (20 – 29.9 Kg will take one 200 mg tablet daily); (30 – 39.9 Kg will take 1.5 tablets daily); (> 40 Kg/adults will take 2 tablets (or 1 table of 400 mg) once daily)
* + Daclatasvir 60 mg/30 mg tablets on daily doses based on body weight or according to the following schedule:
(20 – 30 Kg: will take 30 mg once daily),
(31 – 45 Kg: 45 mg once daily)
(> 45 Kg/adults: 60 mg once daily)
Adherence to the study protocol and medications will be monitored at each visit by counting the number of pills (if any) remained in the medication packets.
Control group
Active

Outcomes
Primary outcome [1] 300523 0
The primary outcome of the trial is non-inferiority in mean differences in the proportion of patients achieving SVR12 (HCV RNA below the lower level of quantification (LLOQ) between the 2 groups.
The response tailored duration (test group) versus the recommended fixed 12 weeks duration (reference group).
The comparison was based on testing the null hypothesis of inferiority of the test group with a pre-specified margin of non-inferiority (NI-margin) of 0.1.

SVR12 Rate is defined as Sustained virologic response rate at 12 weeks after end of treatment.. This will be estimated as rate and percentage of patients who will have serum negativity for hepatitis c virus RNA (virus load below level of quantification) by a polymerase chain reaction (PCR) test, at the end of 12 weeks after completion of therapy.
Timepoint [1] 300523 0
Twelve weeks after end of the treatment course of either 8 or 12 weeks duration.
Secondary outcome [1] 330213 0
rate of suspected unexpected serious and non serious adverse events such as headache, abdominal pain, fatigue that are known to occur with such drug therapy or any other unknown or unexpected drug reactions or hypersensitivity reactions, This will be assessed by asking the patients to report immediately to his treating doctor any adverse event during treatment and also during weekly visits by verbal questionnaire, physical examination and laboratory investigations including complete blood count, renal and liver function tests, abdominal ultrasonographic examination
Timepoint [1] 330213 0
patients are asked to report any adverse event.at any time during treatment
Also during weekly visits by verbal questionnaire, physical examination and laboratory investigations including complete blood count, renal and liver function tests, abdominal ultrasonographic examination
Secondary outcome [2] 331320 0
To evaluate the sensitivity and specificity of the very-rapid virologic response (vRVR) as an on-treatment predictor for SVR12.
Timepoint [2] 331320 0
vRVR is evaluated at 2 weeks after starting therapy,
while SVR12 is evaluated at 12 weeks after the end of treatment course

Eligibility
Key inclusion criteria
1. Males or females "greater than or equal to" 18 years & 'less than or equal to' 80 years of age.
2. Naive chronically infected with Hepatitis C virus (HCV) as evidenced by a positive HCV viral load for more than 6 months.
3. An HCV RNA viral load "greater than or equal to" 10,000 IU/mL at baseline.
4. Willing and able to complete all study visits and procedures.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cirrhosis with Child’s Pugh class C, patients with decompensated cirrhosis, Additionally, patients with cirrhosis are excluded if their AFP is greater than 100ng/ml.
2. History of chronic Hepatitis B infection (HBV) [positive test for hepatitis B surface antigen (HBsAg)], or human immunodeficiency virus (HIV) infection [positive test for anti-HIV Ab] or evidence of other cause of hepatitis.
3. Pregnant/lactating females or married or intended to marry during the whole study period.
4. Uncontrolled diabetes mellitus as evidenced by HbA1C "greater than or equal to" 8.5% at Screening should be treated and blood glucose controlled.
5. Creatinine clearance less than 30 mL/minute.

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 allocation sequence is concealed by being kept in sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The random allocation sequence is generated centrally by software generated block randomization technique.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The comparison is based on testing the null hypothesis of inferiority of the test group with a pre-specified margin of non-inferiority (NI-margin) of 0.1.
H0 (Null hypothesis): (P(reference group) - P(test group) ) >= 0.1 (NI-margin);
H1 (alternative hypothesis): (P(reference group) - P(test group) ) < 0.1 (NI-margin).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
5/06/2016
Date of last participant enrolment
Anticipated
Actual
25/09/2016
Date of last data collection
Anticipated
25/03/2017
Actual
20/03/2017
Sample size
Target
130
Accrual to date
Final
120
Recruitment outside Australia
Country [1] 8519 0
Egypt
State/province [1] 8519 0

Funding & Sponsors
Funding source category [1] 295211 0
Commercial sector/Industry
Name [1] 295211 0
Pharco
Country [1] 295211 0
Egypt
Funding source category [2] 295212 0
Other
Name [2] 295212 0
Abbass Helmy charity
Country [2] 295212 0
Egypt
Primary sponsor type
Other
Name
Green CRC
Address
Green Clinic and Research Center, 27 Green Street, 21121, Alexandria, Egypt.
Country
Egypt
Secondary sponsor category [1] 294040 0
Other
Name [1] 294040 0
National Liver Institute
Address [1] 294040 0
Menofia, Shebin El-Kom 32714, Egypt
Country [1] 294040 0
Egypt
Secondary sponsor category [2] 294923 0
Hospital
Name [2] 294923 0
Alexandria Faculty of medicine Hospital
Address [2] 294923 0
Khartoom Square 21522, Alexandria, Egypt
Country [2] 294923 0
Egypt

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296558 0
Green Clinic and Research Center IRB: IRB00008268
Ethics committee address [1] 296558 0
Green CRC, 27 Green Street 21121, Egypt.
Ethics committee country [1] 296558 0
Egypt
Date submitted for ethics approval [1] 296558 0
05/05/2016
Approval date [1] 296558 0
05/06/2016
Ethics approval number [1] 296558 0

Summary
Brief summary
Efficacy and Safety of Gratisovir (Sofosbuvir) - Daclatasvir Dual Therapy in Egyptian adult and Pediatric Patients with Chronic Hepatitis C Infection.
A prospective, randomized, open-label, non-inferiority, multi-center Study

Objectives:
1. To evaluate the efficacy of Gratisovir (Sofosbuvir) - Daclatasvir dual combination therapy, in Egyptian adult and Pediatric age group patients with chronic hepatitis C.
2. To compare the standard fixed 12 weeks duration of dual SOF/DAC versus a response guided duration of 8/12 in patients with vRVR.
3. To evaluate the safety and tolerability of Sofosbuvir based combination therapy, in Egyptian adult and Pediatric age group patients with chronic hepatitis C
4.. To evaluate the sensitivity and specificity of the very-rapid virologic response as an on-treatment predictor for SVR12.
A randomized, open label, non-inferiority, study designed to test efficacy (SVR12) of the combined Sofosbuvir and Daclatasvir and to compare a suggested response guided shortened duration of 8 weeks of therapy versus the recommended 12 weeks duration.
Eligible adults and children above 10 years old patients with chronic hepatitis c infection will be included and randomized into 2 groups, group 1 will be treated for a fixed 12 weeks duration of dual therapy and group 2 will be treated according to their virologic response at week 2 for either 8 weeks (for those who will have vRVR) or 12 weeks for the rest.
Data will be compared between the 2 groups and the 2 studied durations.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71222 0
Dr Mostafa Yakoot
Address 71222 0
Green Clinic and Research Center,, 27 Green Street, 21121, Alexandria, Egypt.
Country 71222 0
Egypt
Phone 71222 0
+201223927561
Fax 71222 0
Email 71222 0
[email protected]
Contact person for public queries
Name 71223 0
Mostafa Yakoot
Address 71223 0
Green Clinic and Research Center, 27 Green Street, 21121, Alexandria, Egypt.
Country 71223 0
Egypt
Phone 71223 0
+201223927561
Fax 71223 0
Email 71223 0
[email protected]
Contact person for scientific queries
Name 71224 0
Mostafa Yakoot
Address 71224 0
Green Clinic and Research Center, 27 Green Street, 21121, Alexandria, Egypt.
Country 71224 0
Egypt
Phone 71224 0
+201223927561
Fax 71224 0
Email 71224 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
Dimensions AIEffects of dual sofosbuvir/daclatasvir therapy on, chronic hepatitis C infected, survivors of childhood malignancy2019https://doi.org/10.12998/wjcc.v7.i16.2247
N.B. These documents automatically identified may not have been verified by the study sponsor.