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Incidence of de Novo Hepatocellular Carcinoma After Antiviral Agents for HCV.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03775798
Recruitment Status : Recruiting
First Posted : December 14, 2018
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Maria Julia Cremona, Austral University, Argentina

Brief Summary:

The main risk factor for development of hepatocellular carcinoma (HCC) is cirrhosis of any etiology, with an annual incidence risk between 1-6%; currently the leading cause of death in patients with cirrhosis and the 2nd cause of death by cancer worldwide. Chronic hepatitis C (HCV) is the first single cause associated to cirrhosis and HCC in the Western world.

With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of HCC is lower in patients with virologic cure after treatment with pegINF schemes. However, recently published data, open up more controversy regarding the incidence of HCC after virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients treated with DAA has been observed, opening a paradox yet unexplained.

This project proposes to answer the following clinical research question: in patients with HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular carcinoma? To answer this question a prospective longitudinal cohort study of patients with Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.

A minimum of 210 patients will be included with clinical or histological or non-invasive diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without hepatocellular carcinoma at the time of enrollment. From this cohort, patients who develop HCC during follow-up will be identified. Routine screening will be done through ultrasound every 6 months in all subjects enrolled and the diagnosis of HCC will be according to recommendations of European and American guidelines.


Condition or disease Intervention/treatment
Hepatitis C Cirrhosis Antiviral Drug Adverse Reaction Drug: Direct antiviral agents for hepatitis C

Detailed Description:

Name of the study:

INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS WITH HEPATITIS C INFECTION, TRETAED WITH DIRECT ANTIVIRAL AGENTS IN LATIN AMERICA: A MULTICENTER PROSPECTIVE COHORT STUDY

With the advent of new direct antiviral agents (DAA) of chronic HCV infection, virological cure generally exceeds 90% of the cases. Previous studies have shown that the incidence of HCC is lower in patients with virologic cure after treatment with pegINF schemes. However, recently published data, open up more controversy regarding the incidence of HCC after virologic cure with DAA. An increasing incidence of HCC after virologic cure in patients treated with DAA has been observed, opening a paradox yet unexplained.

This project proposes to answer the following clinical research question: in patients with HCV cirrhosis treated with DAA, is there a change in the incidence of hepatocellular carcinoma? To answer this question a prospective longitudinal cohort study of patients with Child Pugh A-B cirrhosis will be held at 3 years minimum follow-up.

A minimum of 210 patients will be included with clinical or histological or non-invasive diagnosis of cirrhosis Child Pugh A or B, with HCV treated with DAA and without hepatocellular carcinoma at the time of enrollement. From this cohort, patients who develop HCC during follow-up will be identified. Routine screening will be done through ultrasound every 6 months in all subjects enrolled and the diagnosis of HCC will be according to recommendations of European and American guidelines.

However, preliminary results presented at the last European Congress of Hepatology in Barcelona, Spain, and early published in Journal of Heaptology, open up more controversy regarding the incidence of HCC after virologic cure post DAA. An unexpected higher incidence and recurrence of HCC after treatment with these new drugs has been observed, opening a paradox yet unexplained. Of particular interest then, is to clarify and find if there is a change in the incidence of HCC in HCV cirrhosis after treatment with DAA in our region. It is relevant on the other hand; that this study would be the first longitudinal cohort study evaluating the development of HCC in patients with cirrhosis in Latin America. It is then expected that the results would be extremely important to the medical science from this region.

Clinical Research Question In patients with HCV cirrhosis treated DAA, is there a change in the incidence of hepatocellular carcinoma? Primary Objective To evaluate the incidence of HCC after treatment with DAA in patients with Child Pugh A or B cirrhosis and chronic HCV infection.

Secondary Objectives

Secondary objectives will be related to:

  • Incidence of HCC between cured and uncured of HCV with DAA.
  • Impact of routine screening on survival in patients with HCC.
  • Risk factors for development of hepatocellular carcinoma in patients with HCV treated with DAA.
  • Adverse events and incidence of cirrhosis decompensation after DAA.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 2200 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 36 Months
Official Title: Incidence of de Novo Hepatocellular Carcinoma After Direct-acting Antiviral Agents for HCV: a Multicenter Prospective Cohort Study From Latin America.
Actual Study Start Date : May 1, 2016
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine



Intervention Details:
  • Drug: Direct antiviral agents for hepatitis C
    Direct-acting antivirals for hepatitis C


Primary Outcome Measures :
  1. Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV [ Time Frame: Three year period ]
    Cumulative incidence, Hazard ratios (95% CI)


Secondary Outcome Measures :
  1. Effectiveness of direct-acting antivirals for HCV [ Time Frame: Three year period ]
    Achievement of RVS

  2. Adverse events after direct-acting antivirals for HCV [ Time Frame: Three year period ]
    Safety



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
A consecutive non-probability sampling of subjects with clinical, histological or non-invasive diagnosis of cirrhosis, functional status Child Pugh class A or B with chronic HCV infection treated with DAA will be made. On a cohort of patients with these characteristics that meet the following eligibility criteria, a minimum 3-year follow-up will be done.
Criteria

Inclusion Criteria:

  • Signed Informed Consent (CI) obtained prior to any study specific procedure. Patients should be able to understand written informed and be ready to sign it (ANNEX I).
  • Men and women 18 years or older.
  • Clinical, histological or non-invasive diagnosis of cirrhosis, according to the American Association for the Study of Liver Diseases, AASLD criteria) [15].
  • Child Pugh A or B (ANNEX II). Child Pugh classification should be calculated based on clinical findings and laboratory results during the selection period.
  • Chronic Hepatitis C, defined as positive viremia with real time PCR method.
  • Current or prior treatment with DAA, including any interferon-free scheme, either in a clinical protocol or treated in the daily practice.
  • Co-infection with HIV infection is allowed or Hepatitis B.

Exclusion Criteria:

  • • Prior diagnosis of Hepatocellular to treatment with DAA.

    • Previous liver transplantation.
    • Drug addiction, medical, psychological or social problems that may interfere with the patient's participation in the study or evaluation of the results.
    • Pregnancy and/or breastfeeding.
    • Close relationship with the research center; eg close family member of the researcher, dependent (eg employee or student research center that could access study records and data CRF).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03775798


Contacts
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Contact: Maria Julia Cremona MCREMONA@austral.edu.ar
Contact: Marcelo Silva, MD msilva@cas.austral.edu.ar

Locations
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Argentina
Universidad Austral Recruiting
Pilar, Buenos Aires, Argentina, 1629
Contact: Marcelo Silva, MD       msilva@cas.austral.edu.ar   
Contact: Federico Piñero, MD, MSCE       fpinerof@cas.austral.edu.ar   
Principal Investigator: Marcelo Silva, MD         
Sponsors and Collaborators
Austral University, Argentina
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Maria Julia Cremona, UIC staff, Austral University, Argentina
ClinicalTrials.gov Identifier: NCT03775798    
Other Study ID Numbers: 17-062
First Posted: December 14, 2018    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Maria Julia Cremona, Austral University, Argentina:
direct acting antivirals
hepatitis c
hepatocellular carcinoma
Additional relevant MeSH terms:
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Hepatitis C
Carcinoma
Carcinoma, Hepatocellular
Hepatitis
Drug-Related Side Effects and Adverse Reactions
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Flaviviridae Infections
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Chemically-Induced Disorders
Antiviral Agents
Anti-Infective Agents