Bleeding Esophageal VaricesPhase 4P-HCCNCT01970748
Primary Prevention of Patients With Hepatocellular Carcinoma and Concomitant Esophageal Varices
A Phase 4 study testing Propranolol and Esophageal variceal ligation in people with Bleeding Esophageal Varices and Hepatocellular Carcinoma, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
Trial summary
Randomized comparison within the endoscopic esophageal varices ligation versus non-selective beta-blocker in the primary prevention of esophageal variceal bleeding in patients with HCC. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Bleeding Esophageal Varices, Hepatocellular Carcinoma
- What is being tested?
- Propranolol and Esophageal variceal ligation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2009to 31 Dec 2025
- Phase
- Phase 4
- 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 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between 20 and 80 years old
- Hepatocellular carcinoma (HCC) associated with esophageal varices
- F2 or F3 esophageal varices (Beppu et al classification)
- Hepatocellular carcinoma (HCC) associated with portal thrombosis
Who cannot join
- History of esophageal variceal bleeding
- Had received endoscopic variceal ligation (EVL) or endoscopic injection sclerotherapy (EIS)
- Pregnancy, or the patients with other terminal illness (such as other terminal cancers, heart failure, renal failure...)
- Propranolol contraindications (such as atrioventricular block, heart failure, chronic obstructive pulmonary disease, asthma, poorly controlled diabetes, severe peripheral arterial disease...)
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Veterans General Hospital
Taipei, 11217
Ming-Chih Hou, MD, 886-2-28712121 ext. 1320, mchou@vghtpe.gov.tw
Han-Chieh Lin, MD, 886-2-28712121 ext. 7506, hclin@vghtpe.gov.tw
About this study
Official title: Endoscopic Treatment Versus Propranolol for Primary Prevention of Patients With Hepatocellular Carcinoma and Concomitant Esophageal Varices
Randomized comparison within the endoscopic esophageal varices ligation versus non-selective beta-blocker in the primary prevention of esophageal variceal bleeding in patients with HCC.
Read the detailed description
Gastroesophageal variceal bleeding is a major complication of cirrhosis and has high rate of rebleeding and mortality. In these 20 to 30 years, medical advances have significantly improved the prognosis of variceal bleeding. Nevertheless, the mortality of gastroesophageal variceal bleeding is still nearly 20 to 30%.
Hepatocellular carcinoma (HCC) is one of the most common malignancy in Asian, and is also the special group in portal hypertension. Studies in Italy, more than 50% of patients diagnosed with HCC are concomitant with esophageal varices. HCC and portal thrombosis caused by HCC itself are all independent risk factors of gastroesophageal bleeding. Once the bleeding, rebleeding rate is up to 50% even if early use of vasoconstrictor agents and endoscopic therapy, which is generally 2 times in patients with cirrhosis.
According to 2010 Baveno V recommendations, non-selective beta-blockers (NSBB) or endoscopic variceal ligation (EVL) are first choice for primary prevention of first variceal bleeding in cirrhotic patients. However, risk factors of variceal bleeding caused by HCC or cirrhosis are different, and portal hypertension is particularly high in patients with HCC and may be combined with portal vein thrombosis. NSBB sufficient to decreased portal hypertension to prevent variceal bleeding is not clear. In Hepatology 2010, Lebrec claimed that NSBB used for cirrhotic patients with refractory ascites had poor prognosis, the main cause of death were the progression of HCC and sepsis, although the impact of NSBB for HCC patients are not entirely clear, but this issue remind clinicians to careful use of NSBB in these patients. Since NSBB possible adverse effects, the use of EVL to prevent bleeding in patents with HCC is superior to NSBB? These need further study to clarify. So we designed this study to evaluate the feasibility and effectiveness of using EVL or NSBB to prevent first bleeding in patients with HCC concomitant with esophageal varices.
- Being tested
- Propranolol, Esophageal variceal ligation
- Keywords
- Variceal bleeding, Portal hypertension, Hepatocellular carcinoma, Endoscopic variceal ligation, Non-selective beta-blocker
- Medical subject headings
- Carcinoma, Hepatocellular, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Also called Inderal, Cardolol
Propranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate>55 or systemic blood pressure>90mmHg)
Esophageal variceal ligationProcedure or surgery
Also called EVL
Esophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy
| Study group | Role | What they receive |
|---|---|---|
| Propranolol | Placebo comparator | Propranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate>55 or systemic blood pressure>90mmHg) Receives: Drug: Propranolol |
| Esophageal variceal ligation | Active comparator | Esophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy. After eradication, follow-up endoscopy every 3 months and variceal ligation again if recurrence. Receives: Procedure: Esophageal variceal ligation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bleeding
Measured: 2 years
Secondary outcomes (1)
Complication survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2013 (estimated)
- Study startAug 2009
- Primary completion25 Dec 2023 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bleeding Esophageal VaricesStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Ming-Chih Hou, MD, Principal investigator, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01970748
- Sponsor's protocol ID
- V101C-016；V102C-094
- Acronym
- P-HCC
- Status last verified
- Aug 2019
- First submitted
- 22 Oct 2013
- Last updated
- 30 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yang TC, Chen WC, Hou MC, Chen PH, Lee PC, Chang CY, Lu HS, Chen YJ, Hsu SJ, Huang HC, Luo JC, Huang YH, Lee FY. Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial. Gut. 2024 Mar 7;73(4):682-690. doi: 10.1136/gutjnl-2023-330419.
PubMed 38123994
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endoscopic Treatment Versus Propranolol for Primary Prevention of Patients With Hepatocellular Carcinoma and Concomitant Esophageal Varices
- ClinicalTrials.gov ID
- NCT01970748
- Acronym / sponsor ID
- P-HCC / V101C-016；V102C-094
- Keywords
- Variceal bleeding, Portal hypertension, Hepatocellular carcinoma, Endoscopic variceal ligation, Non-selective beta-blocker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Study start
- Aug 2009
- Primary completion
- 25 Dec 2023 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 28 Oct 2013 (estimated)
- 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.
Randomized comparison within the endoscopic esophageal varices ligation versus non-selective beta-blocker in the primary prevention of esophageal variceal bleeding in patients with HCC.
Detailed description
Gastroesophageal variceal bleeding is a major complication of cirrhosis and has high rate of rebleeding and mortality. In these 20 to 30 years, medical advances have significantly improved the prognosis of variceal bleeding. Nevertheless, the mortality of gastroesophageal variceal bleeding is still nearly 20 to 30%.
Hepatocellular carcinoma (HCC) is one of the most common malignancy in Asian, and is also the special group in portal hypertension. Studies in Italy, more than 50% of patients diagnosed with HCC are concomitant with esophageal varices. HCC and portal thrombosis caused by HCC itself are all independent risk factors of gastroesophageal bleeding. Once the bleeding, rebleeding rate is up to 50% even if early use of vasoconstrictor agents and endoscopic therapy, which is generally 2 times in patients with cirrhosis.
According to 2010 Baveno V recommendations, non-selective beta-blockers (NSBB) or endoscopic variceal ligation (EVL) are first choice for primary prevention of first variceal bleeding in cirrhotic patients. However, risk factors of variceal bleeding caused by HCC or cirrhosis are different, and portal hypertension is particularly high in patients with HCC and may be combined with portal vein thrombosis. NSBB sufficient to decreased portal hypertension to prevent variceal bleeding is not clear. In Hepatology 2010, Lebrec claimed that NSBB used for cirrhotic patients with refractory ascites had poor prognosis, the main cause of death were the progression of HCC and sepsis, although the impact of NSBB for HCC patients are not entirely clear, but this issue remind clinicians to careful use of NSBB in these patients. Since NSBB possible adverse effects, the use of EVL to prevent bleeding in patents with HCC is superior to NSBB? These need further study to clarify. So we designed this study to evaluate the feasibility and effectiveness of using EVL or NSBB to prevent first bleeding in patients with HCC concomitant with esophageal varices.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propranolol | Placebo comparator | Drug: PropranololPropranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate>55 or systemic blood pressure>90mmHg) |
| Esophageal variceal ligation | Active comparator | Procedure: Esophageal variceal ligationEsophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy. After eradication, follow-up endoscopy every 3 months and variceal ligation again if recurrence. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Between 20 and 80 years old
- Hepatocellular carcinoma (HCC) associated with esophageal varices
- F2 or F3 esophageal varices (Beppu et al classification)
- Hepatocellular carcinoma (HCC) associated with portal thrombosis
Key exclusion criteria (4 listed)
- History of esophageal variceal bleeding
- Had received endoscopic variceal ligation (EVL) or endoscopic injection sclerotherapy (EIS)
- Pregnancy, or the patients with other terminal illness (such as other terminal cancers, heart failure, renal failure...)
- Propranolol contraindications (such as atrioventricular block, heart failure, chronic obstructive pulmonary disease, asthma, poorly controlled diabetes, severe peripheral arterial disease...)
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 |
|---|---|---|
| PropranololAlso: Inderal, CardololPropranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate>55 or systemic blood pressure>90mmHg) | Drug | Propranolol |
| Esophageal variceal ligationAlso: EVLEsophageal variceal ligation every 3-4 weeks to achieve variceal eradication under endoscopy | Procedure or surgery | Esophageal variceal ligation |
Primary outcome
Bleeding
Time frame: 2 years
1 secondary outcome
Complication survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2019.
- Derived from this study: PubMed 38123994Yang TC, Chen WC, Hou MC, Chen PH, Lee PC, Chang CY, Lu HS, Chen YJ, Hsu SJ, Huang HC, Luo JC, Huang YH, Lee FY. Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial. Gut. 2024 Mar 7;73(4):682-690. doi: 10.1136/gutjnl-2023-330419.
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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.
Ming-Chih Hou, MD principal investigator
Taipei Veterans General Hospital, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Propranolol and Esophageal variceal ligation in people with Bleeding Esophageal Varices and Hepatocellular Carcinoma, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
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 4 inclusion and 4 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 30 Aug 2019. 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 Taiwan. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Ming-Chih Hou, MD (886-2-28712121 ext. 1320, mchou@vghtpe.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bleeding (time frame: 2 years). 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 NCT01970748, which also lists 1 linked publication.
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 30 Aug 2019.