Efficacy and Safety of Daclatasvir plus Sofosbuvir for Treatment-

Naïve and Treatment-Experienced Egyptian Patients with Hepatitis C

virus Infection

‫فاعلية و سالمة عقارى دكالتاسفير وسوفوسبوفير لعالج المرضى المصريين المصابين بالفيروس الكبدى (سى) ممن سبق أو لم يسبق لهم العالج‬
 Islam Nasr Abd El Ghaffar Nasr
 B Pharm -Faculty of Pharmacy, Alexandria University
 Clinical pharmacist in Oncology Department
 El-Qabbary Hospital, Alexandria , Ministry of Health, Egypt
 BPS & BCOP
The prevalence of HCV
The treatment of HCV

 A new era of hepatitis C virus treatment has begun in the last few years; the ultimate
goals of which were directly targeting the virus, shortening the length of therapy,
improving sustained virologic response rates, and minimizing side effects. Several new
concepts arose with the development of Directly Acting Antivirals (DAAs) to treat
hepatitis C.
 Sofosbuvir, a potent inhibitor of the HCV nonstructural proteins 5B nucleoside
polymerase inhibitors (NS5B polymerase inhibitors) has recently been approved for the
treatment of HCV in Egypt.
 Daclatasvir inhibits the HCV nonstructural protein NS5A  Recent research suggests that
it targets two steps of the viral replication process, enabling rapid decline of HCV
RNA.
Target of thesis

 Daclatasvir has been used as treatment in combination regimens with PEG-IFN/RIB, as

well as with other DAA agents including sofosbuvir. But, as little is known about the
efficacy & safety of these combinations in Egypt especially with the recently used
DAA agents. We hope that this work can add in discovering the real aspects of this
combination.

The aim of this work is to assess the efficacy and safety of daclatasvir plus sofosbuvir for
treatment-naïve and treatment-experienced Egyptian patients with hepatitis C virus infection
Subjects and Methods
 Subjects:

 Study setting: El-Qabbary Hospital, Alexandria, Egypt

 Study population: chronic HCV infection Egyptian patients presented at the outpatients
clinic with the following eligibility criteria

 Inclusion criteria (According to The Egyptian Ministry of Health Protocol)(8)

 Patients are
1. at least 18 years old
2. with plasma HCV RNA ≥ 104 IU/mL
3. either HCV treatment naïve or experienced
4. should have compensated cirrhosis (based on clinical, laboratory and ultrasound evaluation)
 Exclusion criteria (According to The Egyptian Ministry of Health Protocol) (8)

 Pregnant or lactating females or any female with childbearing potential not practicing adequate contraception
 Patients with evidence of medical condition contributing to chronic liver disease other than HCV
 Patients with any of the following conditions or characteristics will be excluded from participation:
1. Body mass index (BMI) <18 kg/m2;
2. Decompensated liver disease ( in the form of either esophageal variceal bleeding, ascites, spontaneous bacterial
peritonitis, hepatic encephalopathy, hepatorenal syndrome or hepatocellular carcinoma)
3. Chronic use of systemically administered immunosuppressive agents, such as prednisone equivalent >10 mg /day
4. Chronic liver disease of a non-HCV etiology; HIV infection, hepatitis B virus infection; or excessive alcohol
ingestion (defined as >3 glasses/day).
5. Creatinine clearance <60 mL/min as calculated by the Cockcroft-Gault equation
6. Blood hemoglobin <11 g/dL for females and <12 g/dL for males
7. Blood platelet count ≤ 50,000/mm3;
8. Serum level of direct bilirubin ≥ 1.5 times the upper limit of normal (1.5×ULN)
9. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase >10 ×
ULN;
10. Hemoglobin A1c >10%
11. History of malignancy diagnosed or treated within the prior 5 years

12. Arrhythmic patients

 Sample size:

 A total sample size of 406 chronic HCV patients is sufficient to detect a SVR of 90%
with a margin error of 4% with 95% confidence, after compensation for an the expected
non- response rate (completeness of records) of 20%
 Methods

 Study design:

 A local, one center, non-interventional, retrospective cohort study

 Treatment regimen and duration:

 Sofosbuvir: 400 mg tablet. Taken orally, once daily with or without food for 12 weeks

 Daclatasvir: 60 mg tablet. Taken orally, once daily with or without food for 12 weeks
 Study endpoints:

 Primary Efficacy End Point:

1. Rapid virologic response (RVR) rate which is defined as undetectable serum HCV RNA
(level of <25 IU per milliliter) at week 4 after the end of therapy.
2. Sustained virologic response (SVR) rate which is defined as undetectable serum HCV RNA
(level of <25 IU per milliliter) at week 12 after the end of therapy.

  

 Primary Safety End Point:

 Number of participants experiencing serious adverse events (SAEs)
a) Anemia
b) Hepato-renal syndrome
c) Hepatic toxicity and cirrhosis
d) Arrhythmia
 Baseline Assessment:

 According to the Egyptian Ministry of Health Protocol, all patients eligible for treatment
will be subjected to the following:

1. Medical history and clinical examination with stress on BMI calculation and history of any
of the exclusion criteria
2. Routine laboratory investigations, including complete blood picture, blood urea, and serum
creatinine. Creatinine clearance will be calculated by the Cockcroft-Gault equation.
3. Electrocardiographic examination (ECG)
4. Abdominal imaging by ultrasound to assess ascites and exclude hepatocellular carcinoma
5. Upper gastrointestinal endoscopy to exclude grade 3 and 4 esophageal varices
6. Hepatic function panel, including AST , ALT , Alkaline phosphatase, bilirubin, albumin,
International Normalized Ratio (INR) and alpha-fetoprotein
7. Hepatitis C viral load (HCV RNA) by quantitative polymerase chain reaction (PCR)
 Patients follow up:

1. Patients will be followed up at weeks 4, 8, 12 after starting treatment to detect serious adverse
events (SAEs).
2. Patients will be followed up at weeks 4, 12 after the end of therapy to detect Rapid virologic
response (RVR) rates and Sustained virologic response (SVR) rates

 In each follow up visit, they will be subjected to:

1. Medical history and clinical examination with stress on epilepsy and arrhythmia
2. Routine laboratory investigations, including complete blood picture, blood urea and serum
creatinine. Creatinine clearance will be calculated by the Cockcroft-Gault equation to assess
hepato-renal syndrome and anemia.
3. Electrocardiographic examination (ECG) to assess developing arrhythmia
4. Hepatic function panel, including AST , ALT , alkaline phosphatase, bilirubin, albumin, INR &
alpha-feto protein to assess Hepatotoxicity and cirrhosis
5. Hepatitis C viral load (HCV RNA) by quantitative polymerase chain reaction (PCR) to assess
efficacy end points
6. Patient drop out and its causes and patient mortality will be recorded.
Thanks