Dr. Iram Shad PGT-Medicine MU-1, HFH,RWP SAFETY PROFILE OF SOFOSBUVIR-BASED TRIPLE THERAPY IN HEPATITIS C GENOTYPE-3 INFECTION Dr. Iram Shad PGT-Medicine MU-1, HFH,RWP

INTRODUCTION Hepatitis C is a global health issue. It is one of the common causes of cirrhosis, end-stage liver disease and hepatocellular carcinoma. Sofosbuvir is a novel nucleotide analogue inhibitor of hepatitis C virus (HCV) NS5B polymerase that has recently been approved by the Federal Drug Administration department of United States of America for the treatment of HCV.

Sofosbuvir in combination with pegylated interferon and ribavirin has better clinical and laboratory safety profile than standard treatment. Rates of treatment discontinuation and dose reduction with sofosbuvir containing regimens are lower than those commonly observed with standard regimen.

RATIONALE OF STUDY The rationale of current study is to gather the safety data of Sofosbuvir combined with standard treatment in comparison with the standard treatment alone in our settings. This will help us in devising our local guidelines compatible with international ones for utilization of this new drug in the clinical settings.

STUDY OBJECTIVE HYPOTHESIS (H0): To compare the treatment discontinuation rate due to adverse events in patients receiving Sofosbuvir combined with standard treatment in comparison with the standard treatment alone at 12 weeks. HYPOTHESIS (H0): There is no difference in the treatment discontinuation rate due to adverse events in both groups at 12 weeks

STUDY DESIGN: SETTING: DURATION OF STUDY: SAMPLE SIZE: Randomized controlled trial SETTING: Study will be conducted at Centre for Liver and Digestive Diseases (CLD), Holy Family Hospital, (HFH) Rawalpindi. DURATION OF STUDY: 06 months after the acceptance of synopsis. SAMPLE SIZE: 258 patients. SAMPLING TECHNIQUE: Simple random sampling technique through lottery method.

INCLUSION CRITERIA: All diagnosed cases of hepatitis C infection with Genotype 3 confirmed through PCR quantitative and genotyping test Age > 18 years, both genders. Written informed consent to participate in the study.

EXCLUSION CRITERIA: Patients with history of previous treatment for HCV HBsAg positive patients (on ELISA) Patients with history of suffering from other chronic medical illnesses like diabetes, chronic renal failure or congestive cardiac failure Patients with history of suffering from any psychiatric illness Pregnant or nursing female, or male with pregnant female partner Current or prior history of clinical hepatic decompensation History of clinically-significant illness or any other major medical disorder that may have interfered with subject treatment, assessment, or compliance with the protocol Excessive alcohol consumption or significant drug abuse

DATA COLLECTION TECHNIQUE: After seeking permission from the Ethical commite of RMC and hospital authorities, all the patients fulfilling the required will be explained the purpose and procedure of the study. After taking written informed consent, patients will be enrolled in the study. The information regarding demographic characteristics and clinical presentation of the selected patients will be recorded. All the patients will be assigned to the two treatment groups.

Group I will comprise of patients who will receive oral sofosbuvir, peginterferon and oral ribavirin. Group II will comprise of patients who will receive standard treatment i.e., peginterferon and oral ribavirin. Adverse events will be recorded in both groups and the percentage of patients who will discontinue treatment due to adverse events till 12 weeks of treatment will also be noted and recorded on the prescribed proforma.

DATA ANALYSIS PROCEDURE: Data will be entered and analyzed using SPSS software version 17.0. The continuous numerical variables like age will be calculated as mean and standard deviations. Categorical variables like gender, presence or absence of adverse events and treatment discontinuation rate will be represented as frequency and percentage in both groups. The treatment discontinuation rate will be compared in both groups using chi-square test at 5% level of significance. A p- value of <0.05 will be considered significant.