Hepatitis B, ChronicNCT07459426
Entecavir Resistance-Associated Mutations in Chronic HBV Patients in Turkey (STREAM Study)
An observational study of Hepatitis B, Chronic, run by Yaşar Bayındır, MD at 10 sites in Turkey (Türkiye).
Trial summary
Chronic hepatitis B is a long-term viral infection that affects millions of people worldwide. Patients usually require lifelong antiviral treatment to control the virus and prevent liver damage. Some older antiviral medications, such as lamivudine, can lead to the development of viral resistance. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Viral genetic material from blood samples using advanced sequencing technology
- How many people
- 700 participants
- Where
- 10 sitesTurkey (Türkiye)
- Study dates
- 15 Mar 2026to 15 Sep 2027
- Phase
- Observational
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult (≥18 years) HBsAg-positive patients with a documented history of lamivudine therapy for ≥6 months who were subsequently switched to tenofovir-based therapy (ADV, TDF, or TAF) and have not received entecavir or telbivudine.
Who may be able to join
- Age ≥18 years
- HBsAg positive
- Group 1: Either treatment-naïve participants with HBV DNA>2000 IU/ml
- Group 2: Prior lamivudine therapy ≥6 months with switch to ADVor TDF or TAF
- Ability to provide informed consent
Who cannot join
- Prior entecavir exposure
- Prior telbivudine exposure
- Age <18 years
- Inability to provide informed consent Note: Previous adefovir or (pegylated) interferon use is not an exclusion criterion.
- Patients with insufficient sample volume or inadequate DNA quality for sequencing will be excluded from final analysis.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
Turkey (Türkiye)10 sites, 10 recruiting
- Not yet recruiting
Cukurova University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
Adana
Yesim Tasova, MD, Prof., +905353088511, ytasova@gmail.com
Yesim Tasova, MD, Prof.
- Not yet recruiting
Gazi University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
Ankara
Yesim Yildiz, MD, Assoc. Prof., +905556109871, yesim_2323_1989@hotmail.com
Yesim Yildiz, MD, Assoc. Prof.
- Not yet recruiting
Health Sciences University Hamidiye Faculty of Medicine
Ankara
Funda Simsek, MD, Prof., +905325620953, fundasimsek67@gmail.com
Funda Simsek, MD, Assoc. Prof.
- Not yet recruiting
Akdeniz University, Faculty of Medicine
Antalya
Dilara Inan, MD, Prof., +905323706725, inan@akdeniz.edu.tr
Dilara Inan, MD, Prof.
- Recruiting
Dicle University, Faculty of Medicine
Diyarbakır
Mustafa Kemal Celen, MD, Prof., +905336207022, mkcelen@hotmail.com
Cigdem Mermutluoglu, MD., Assoc. Prof., +905052252700, cigdemmermut@gmail.com
- Recruiting
Gaziantep University
Gaziantep
Ayse Ozlem Mete, MD, +905064883309, ayseozlem_ornek@hotmail.com
Ilkay Karaoglan, MD, Prof., +905359266763, ilkayn.can@gmail.com
- Not yet recruiting
Ege University, Faculty of Medicine
Izmir
Tansu Yamazhan, MD, Prof., 905325060470, tansuyamazhan@gmail.com
Tansu Yamazhan, MD, Prof.
- Not yet recruiting
Kocaeli University, Faculty of Medicine
Kocaeli
Sila Akhan, MD, Prof., +905322666535, sila.akhan@kocaeli.edu.tr
Sila Akha, MD, Prof.
- Not yet recruiting
İnönü University, Faculty of Medicine, Department of Clinical Microbiology
Malatya
Baris Otlu, PhD, Prof., +905333710780, botlu@yahoo.com
Baris Otlu, PhD, Prof.
- Not yet recruiting
Samsun Ondokuz Mayıs University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
Samsun
Ozgur Gunal, MD, Prof., +905052543167, ozgurgop@yahoo.com
Ozgur Gunal, MD, Prof.
About this study
Official title: Sequencing-Based Tracking of Entecavir Resistance-Associated Mutations in Chronic Hepatitis B Patients: A Multicenter Observational Study (STREAM)
Chronic hepatitis B is a long-term viral infection that affects millions of people worldwide. Patients usually require lifelong antiviral treatment to control the virus and prevent liver damage.
Some older antiviral medications, such as lamivudine, can lead to the development of viral resistance. This means the virus changes in a way that makes certain treatments less effective. Even though newer drugs like entecavir are stronger and more resistant to these changes, previous exposure to lamivudine may increase the risk of developing additional resistance mutations.
By analyzing viral genetic material from blood samples using advanced sequencing technology, this research will help improve understanding of antiviral resistance patterns in patients with chronic hepatitis B in Turkey and may support better treatment decisions in the future.
Read the detailed description
Hypothesis
- Entecavir resistance-associated mutations are detectable in both naïve and lamivudine-experienced patients.
- Prevalence is higher in lamivudine-experienced patients compared to treatment-naïve patients.
- Longer lamivudine exposure and higher HBV-DNA are associated with resistance.
- Nanopore sequencing detects minor resistance variants not captured by conventional methods.
Sample size: 700 estimated participants
Pre-existing lamivudine-induced resistance mutations create a genetic background that facilitates the emergence of secondary entecavir resistance mutations, even in patients currently receiving tenofovir-based therapy.
Investigators further hypothesize that peripheral blood-derived cccDNA sequencing can serve as a minimally invasive method to characterize transmitted and acquired resistance mutation profiles in chronic HBV infection.
Clinical Significance Chronic hepatitis B management relies on long-term antiviral therapy, and resistance-associated mutations significantly influence treatment success and future therapeutic strategies.
Although entecavir has a high genetic barrier, prior lamivudine exposure may predispose patients to secondary resistance mutations, potentially compromising antiviral efficacy. However, the prevalence and distribution of such mutations in the Turkish HBV population remain insufficiently characterized
This study will provide:
- National-level data on entecavir resistance-associated mutations
- Comparative analysis between treatment-naïve and lamivudine-experienced patients
- Insight into the clinical relevance of minor resistance variants detected by long-read sequencing Peripheral blood-derived cccDNA sequencing may represent a minimally invasive resistance monitoring tool.
The findings may contribute to optimizing antiviral selection strategies, guiding individualized treatment decisions, and informing national hepatitis B management policies.
This study will provide national-level data on entecavir resistance mutations in Turkey.
It may support individualized antiviral selection and contribute to national HBV management strategies.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Viral genetic material from blood samples using advanced sequencing technology
- Keywords
- Chronic hepatitis B, Lamivudine, Entecavir, Antiviral resistance
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Viral genetic material from blood samples using advanced sequencing technologyDiagnostic test
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Treatment-Naïve Chronic HBV Patients | Adult (≥18 years) HBsAg-positive patients with HBV-DNA >2,000 IU/mL who have not received prior nucleos(t)ide analogue therapy. Receives: Diagnostic Test: Viral genetic material from blood samples using advanced sequencing technology | |
| Lamivudine-Experienced Chronic HBV Patients | Adult (≥18 years) HBsAg-positive patients with a documented history of lamivudine therapy for ≥6 months who were subsequently switched to tenofovir-based therapy (ADV, TDF, or TAF) and have not received entecavir or telbivudine. Receives: Diagnostic Test: Viral genetic material from blood samples using advanced sequencing technology |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of entecavir resistance-associated mutations in the HBV polymerase/RT region detected by Oxford Nanopore sequencing.
Detection of entecavir resistance-associated mutations (T184, S202, M250), with or without lamivudine resistance background mutations (L180M, M204V/I), in the HBV polymerase/RT region by Oxford Nanopore sequencing of peripheral blood-derived cccDNA. Mutations will be reported if detected at an allele frequency ≥5%.
Measured: March 15th, 2026-March 15th, 2027
Secondary outcomes (4)
Comparison of mutations between two groups.
Comparison of mutation frequency between treatment-naïve and lamivudine-experienced patients.
Comparison of mutation frequency between treatment-naïve and lamivudine-experienced patients.
Comparison of mutation frequency between treatment-naïve and lamivudine-experienced patients.
Measured: March 15th, 2026-March 15th, 2027
Association between HBV-DNA level and resistance-associated mutation presence.
Association between HBV-DNA level and resistance-associated mutation presence in all groups.
Measured: March 15th, 2026-March 15th, 2027
Duration of lamivudine exposure and secondary mutations.
Association between duration of lamivudine exposure and secondary mutations.
Measured: March 15th, 2026-March 15th, 2027
Classical lamivudine resistance mutations and their co-occurrence with ETV resistance mutations.
Detection of classical lamivudine resistance mutations (M204V/I, L180M) and their co-occurrence with ETV resistance mutations.
Measured: March 15th, 2026-March 15th, 2027
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start15 Mar 2026
- Primary completion15 Dec 2026 (estimated)
- Study completion15 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies 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
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yaşar Bayındır, MD
- Sponsor type
- University, hospital or other
- Collaborators
- SOUTHEAST NEUROLOGY AND INFECTIOUS DISEASES SOCIETY
- Responsible party
- Sponsor-investigator, Yaşar Bayındır, MD, Guven Health Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07459426
- Sponsor's protocol ID
- STREAM Study-GVN
- Status last verified
- Sep 2026
- First submitted
- 28 Feb 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Prevalence of entecavir resistance-associated mutations in the HBV polymerase/RT region detected by Oxford Nanopore sequencing.