Effect of Cyclosporine A Versus Tacrolimus on Response to Antiviral Therapy After Hepatitis C Genotype -4 Recurrence Post Liver Transplantation

NCT03665766 | Completed FDA Drug

• 1 other identifier: ASU-1124568
• Study Type: observational
• Target: 126
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background and Aim: The immunosuppression influence on the response to antiviral therapy (AVT) for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients remains controversial, especially for the rarely investigated genotype 4.This study aims to compare the effects of the two widely used calcineurin inhibitors(CNIs)(Cyclosporine A (CsA) and tacrolimus (Tac)) on the therapeutic response to different AVT regimens. Method: In126 living donor liver transplant (LDLT) recipients with recurrent HCV infection, participants were categorized to three groups according to AVT. Group one received pegylated interferon (Peg IFN-α 2a) and ribavirin (RBV) (n= 44), group two received the direct antiviral agent (DAA) sofosbuvir plus RBV (n=52) and group three received daclatasvir, sofosbuvir (other DAAs) plus RBV(n=30) each group was further subdivided according to primary immunosuppression (CsA or Tac). The sustained virological response (SVR) and relapse rates were considered the primary therapeutic outcomes of AVT. The virological response guided therapy end points for AVT were considered the secondary outcomes.

Conditions

Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• sustained virological response

  a negative serum HCV RNA

  24 weeks for group I and 12 weeks for group II and III

Study Arms (6)

IFN group received Cyclosporine

Living donor liver transplantation recipients with recurrent HCV received Peg IFN-α 2a and RBV as antiviral therapy and Cyclosporine A as primary immunosuppression ,this was routinely taken not as intervention according to local practice

Drug: Cycloserine,Tacrolimus

IFN group received tacrolimus

Living donor liver transplantation recipients with recurrent HCV received Peg IFN-α 2a and RBV as antiviral therapy and Tacrolimus as primary immunosuppression ,this was routinely taken not as interventing according to local practice

Drug: Cycloserine,Tacrolimus

Sof plus Rbv group received Cyclosporine

Living donor liver transplantation recipients with recurrent HCV received sofosbuvir and RBV as antiviral therapy and Cyclosporine as primary immunosuppression,this was routinely taken not as intervention according to local practice

Drug: Cycloserine,Tacrolimus

Sof plus Rbv received tacrolimus

Living donor liver transplantation recipients with recurrent HCV received sofosbuvir and RBV as antiviral therapy and Tacrolimus as primary immunosuppression,this was routinely taken not as intervention according to local practice

Drug: Cycloserine,Tacrolimus

Sof,dac pus ribavirin received cyclosporine

Living donor liver transplantation recipients with recurrent HCV received daclatasvir, sofosbuvir and RBV as antiviral therapy and Cyclosporine as primary immunosuppression,this was routinely taken not as intervention according to local practice

Drug: Cycloserine,Tacrolimus

sof,dac plus rbv received tacrolimus

Living donor liver transplantation recipients with recurrent HCV received daclatasvir, sofosbuvir and RBV as antiviral therapy and Tacrolimus as primary immunosuppression,this was routinely taken not as intervention according to local practice

Drug: Cycloserine,Tacrolimus

Interventions

Cycloserine,Tacrolimus DRUG

IFN group received Cyclosporine; IFN group received tacrolimus; Sof plus Rbv group received Cyclosporine; Sof plus Rbv received tacrolimus; Sof,dac pus ribavirin received cyclosporine; sof,dac plus rbv received tacrolimus

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

living donor liver transplant (LDLT) recipients with recurrent HCV infection, participants were categorized to three groups according to AVT. Group one received pegylated interferon (Peg IFN-α 2a) and ribavirin (RBV) , group two received the direct antiviral agent (DAA) sofosbuvir plus RBV and group three received daclatasvir, sofosbuvir (other DAAs) plus RBV each group was further subdivided according to primary immunosuppression (CsA or Tac)

You may qualify if:

• Age between 18 and 65 years ;
• elevated aminotransferase levels (ALT and AST)
• detectable HCV RNA by polymerase chain reaction (PCR)
• liver biopsy results consistent with HCV recurrence using the Metavir scoring system (Metavir ≥A1F1)
• For group II and III:
• age between 18 and 75 years
• detectable HCV RNA by PCR

You may not qualify if:

• if they were younger than 18 years or older than 65 years or had one of the following criteria
• alcoholic
• poorly controlled autoimmune disease
• significant cardiac disease
• suicidal ideation
• a history of suicide attempt
• major psychosis
• serum creatinine ˃3 mg/dl
• thyroid dysfunction
• combined kidney-liver transplantation
• were currently pregnant or planning pregnancy.
• Group II and III:
• younger than 18 years or older than 75 years
• total bilirubin (T.Bil) \>3 mg/dl
• serum albumin\< 2.8 mg/dl

Sponsors & Collaborators

• Ain Shams University: lead

MeSH Terms

Interventions

Cycloserine; Tacrolimus

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor -Tropical medicine-faculty of medicine-Ain Shams University

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: September 11, 2018
• Study Start: May 15, 2014
• Primary Completion: April 2, 2018
• Study Completion: April 2, 2018
• Last Updated: September 11, 2018

Record last verified: 2018-09