Hepatitis CNCT03775798
Incidence of de Novo Hepatocellular Carcinoma After Antiviral Agents for HCV.
An observational study of Hepatitis C and Cirrhosis, run by Austral University, Argentina at 1 site in Argentina.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Cirrhosis, Antiviral Drug Adverse Reaction
- What is being tested?
- Direct antiviral agents for hepatitis C
- How many people
- 2,200 participants
- Where
- 1 siteArgentina
- Study dates
- 1 May 2016to 1 Jan 2021
- How long will I take part?
- 36 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- • 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).
Trial locations and contacts
1 site in 1 country.
Maria Julia Cremona contact
Marcelo Silva, MD contact
Argentina1 site, 1 recruiting
- Recruiting
Universidad Austral
Pilar, Buenos Aires, 1629
Marcelo Silva, MD, msilva@cas.austral.edu.ar
Federico Piñero, MD, MSCE, fpinerof@cas.austral.edu.ar
About this study
Official title: Incidence of de Novo Hepatocellular Carcinoma After Direct-acting Antiviral Agents for HCV: a Multicenter Prospective Cohort Study From Latin America.
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.
Read more
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.
Read the 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.
- Conditions
- Hepatitis C, Cirrhosis, Antiviral Drug Adverse Reaction
- Being tested
- Direct antiviral agents for hepatitis C
- Keywords
- direct acting antivirals, hepatitis c, hepatocellular carcinoma
- Medical subject headings
- Hepatitis C, Fibrosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct antiviral agents for hepatitis CDrug
Direct-acting antivirals for hepatitis C
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV
Cumulative incidence, Hazard ratios (95% CI)
Measured: Three year period
Secondary outcomes (2)
Effectiveness of direct-acting antivirals for HCV
Achievement of RVS
Measured: Three year period
Adverse events after direct-acting antivirals for HCV
Safety
Measured: Three year period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2018
- Study start1 May 2016
- Primary completion1 Dec 2020 (estimated)
- Study completion1 Jan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,200 participants (estimated)
- Target duration
- 36 Months
Sponsor and investigators
- Lead sponsor
- Austral University, Argentina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Julia Cremona, Austral University, Argentina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03775798
- Sponsor's protocol ID
- 17-062
- Status last verified
- Dec 2018
- First submitted
- 12 Dec 2018
- Last updated
- 19 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Braillon A. Achieving Virological Response in Patients With Hepatitis C Is Only Half Way for Effective Care. Clin Gastroenterol Hepatol. 2021 Mar;19(3):622-623. doi: 10.1016/j.cgh.2020.04.086. Epub 2020 Nov 26. No abstract available.
PubMed 33248099Ridruejo E, Pinero F, Mendizabal M, Cheinquer H, Wolff FH, Anders M, Reggiardo V, Ameigeiras B, Palazzo A, Alonso C, Schinoni MI, Zuain MGV, Tanno F, Figueroa S, Santos L, Peralta M, Soza A, Vistarini C, Adrover R, Fernandez N, Perez D, Hernandez N, Estepo C, Bruno A, Descalzi V, Sixto M, Borzi S, Cocozzella D, Zerega A, de Araujo A, Varon A, Silva M; Latin American Liver Research Educational and Awareness Network (LALREAN). Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort. J Med Virol. 2020 Dec;92(12):3545-3555. doi: 10.1002/jmv.26383. Epub 2020 Aug 13.
PubMed 32749710Mendizabal M, Pinero F, Ridruejo E, Herz Wolff F, Anders M, Reggiardo V, Ameigeiras B, Palazzo A, Alonso C, Schinoni MI, Videla Zuain MG, Tanno F, Figueroa S, Santos L, Peralta M, Soza A, Vistarini C, Adrover R, Fernandez N, Perez D, Hernandez N, Estepo C, Bruno A, Descalzi V, Sixto M, Borzi S, Cocozzella D, Zerega A, de Araujo A, Varon A, Rubinstein F, Cheinquer H, Silva M; Latin American Liver Research; Educational and Awareness Network (LALREAN). Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2554-2563.e3. doi: 10.1016/j.cgh.2020.02.044. Epub 2020 Feb 28.
PubMed 32113892
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incidence of de Novo Hepatocellular Carcinoma After Direct-acting Antiviral Agents for HCV: a Multicenter Prospective Cohort Study From Latin America.
- ClinicalTrials.gov ID
- NCT03775798
- Acronym / sponsor ID
- 17-062
- Conditions
- Hepatitis C, Cirrhosis, Antiviral Drug Adverse Reaction
- Keywords
- direct acting antivirals, hepatitis c, hepatocellular carcinoma
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,200 participants (estimated)
- Lead sponsor
- Austral University, ArgentinaUniversity, hospital or other
- Study start
- 1 May 2016 (actual)
- Primary completion
- 1 Dec 2020 (estimated)
- Study completion
- 1 Jan 2021 (estimated)
- First posted
- 14 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 36 Months
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- • Prior diagnosis of Hepatocellular to treatment with DAA.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Direct antiviral agents for hepatitis CDirect-acting antivirals for hepatitis C | Drug | – |
Primary outcome
Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV
Time frame: Three year period
Cumulative incidence, Hazard ratios (95% CI)
2 secondary outcomes
Effectiveness of direct-acting antivirals for HCV
Time frame: Three year period
Adverse events after direct-acting antivirals for HCV
Time frame: Three year period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
- Derived from this study: PubMed 33248099Braillon A. Achieving Virological Response in Patients With Hepatitis C Is Only Half Way for Effective Care. Clin Gastroenterol Hepatol. 2021 Mar;19(3):622-623. doi: 10.1016/j.cgh.2020.04.086. Epub 2020 Nov 26. No abstract available.
- Derived from this study: PubMed 32749710Ridruejo E, Pinero F, Mendizabal M, Cheinquer H, Wolff FH, Anders M, Reggiardo V, Ameigeiras B, Palazzo A, Alonso C, Schinoni MI, Zuain MGV, Tanno F, Figueroa S, Santos L, Peralta M, Soza A, Vistarini C, Adrover R, Fernandez N, Perez D, Hernandez N, Estepo C, Bruno A, Descalzi V, Sixto M, Borzi S, Cocozzella D, Zerega A, de Araujo A, Varon A, Silva M; Latin American Liver Research Educational and Awareness Network (LALREAN). Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort. J Med Virol. 2020 Dec;92(12):3545-3555. doi: 10.1002/jmv.26383. Epub 2020 Aug 13.
- Derived from this study: PubMed 32113892Mendizabal M, Pinero F, Ridruejo E, Herz Wolff F, Anders M, Reggiardo V, Ameigeiras B, Palazzo A, Alonso C, Schinoni MI, Videla Zuain MG, Tanno F, Figueroa S, Santos L, Peralta M, Soza A, Vistarini C, Adrover R, Fernandez N, Perez D, Hernandez N, Estepo C, Bruno A, Descalzi V, Sixto M, Borzi S, Cocozzella D, Zerega A, de Araujo A, Varon A, Rubinstein F, Cheinquer H, Silva M; Latin American Liver Research; Educational and Awareness Network (LALREAN). Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2554-2563.e3. doi: 10.1016/j.cgh.2020.02.044. Epub 2020 Feb 28.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Julia Cremona contact
Marcelo Silva, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis C and Cirrhosis, run by Austral University, Argentina at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria Julia Cremona (MCREMONA@austral.edu.ar), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of hepatocellular carcinoma after direct-acting antivirals for HCV (time frame: Three year period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03775798, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2018.