Liver CirrhosesNCT04254822
HVPG-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Cirrhotic Patients
A study testing Transjugular intrahepatic portosystemic shunt, Carvedilol and Endoscopic variceal ligation in people with Liver Cirrhoses and Variceal Hemorrhage, run by Air Force Military Medical University, China at 1 site in China.
Trial summary
Variceal bleeding is a major complication of cirrhosis, associated with a hospital mortality rate of 10%-20%. Surviving patients are at high risk for recurrent hemorrhage. For these reasons, management should be directed at its prevention. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhoses, Variceal Hemorrhage, Esophageal Varices
- What is being tested?
- Transjugular intrahepatic portosystemic shunt, Carvedilol and Endoscopic variceal ligation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2020to 31 Dec 2023
- Phase
- Interventional
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of liver cirrhosis
- History of esophageal variceal bleeding confirmed by endoscopy
- Time interval between index bleeding and randomization > 5 days.
- Child-Pugh score < 12，MELD score<19
Who cannot join
- Clinical manifestation of active bleeding
- Gastric variceal bleeding: GOV2，IGV1 or IGV2
- Degree of main portal vein thrombosis > 50%
- Refractory ascites
- Contraindications of TIPS
- Contraindications of NSBB
Show all 13Show fewer
- Budd-Chiari Syndrome
- Malignancy tumor
- Uncontrolled infections
- History of portal-systemic shunt surgery
- HIV
- Pregnancy or breastfeeding woman
- Poor incompliance
Trial locations and contacts
1 site in 1 country.
China1 site
Fourth Military Medical University
Xi'an, Shaanxi, 710032
Jun Tie, MD. Ph.D., +862984771537, tiejun7776@163.com
Hui Chen, MD. Ph.D., +862984771537, qychenhui@163.com
About this study
Official title: Hepatic Vein Pressure Gradient(HVPG)-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Patients With Liver Cirrhosis: A Prospective Randomized Controlled Trial
Variceal bleeding is a major complication of cirrhosis, associated with a hospital mortality rate of 10%-20%. Surviving patients are at high risk for recurrent hemorrhage. For these reasons, management should be directed at its prevention. Endoscopic variceal band ligation (EBL) in combination with non-selective β-blocker (NSBB) therapy is the recommended first line therapy. Transjugular intrahepatic portosystemic stent-shunt (TIPS) is the most effective method to prevent rebleeding, however, it is burdened with increased hepatic encephalopathy and deterioration of liver function in patients with advanced cirrhosis. So TIPS placement forms an alternative if first line therapy fails.
Hepatic venous pressure gradient (HVPG) is currently the best available method to evaluate the presence and severity of portal hypertension. Patients who experience a reduction in HVPG of ≥20% or to <12mmHg in response to drug therapy are defined as 'responders'. The lowest rebleeding rates are observed in patients on secondary prophylaxis who are HVPG responders. A recent meta-analysis has demonstrated that combination therapy is only marginally more effective than drug therapy. This suggests that pharmacological therapy is the cornerstone of combination therapy. Adding EBL may not be the optimal approach to improve the outcome of HVPG nonresponders and HVPG non-responders are a special high-risk population that may benefit from a more aggressive approach, such as an early decision for TIPS. It recently was shown that TIPS placement within 72 hours after acute bleeding not only prevented recurrent bleeding but also improved survival. These raise the question of whether ligation together with NSBB should remain the first choice for elective secondary prophylaxis.
Therefore, the purpose of the study is to compare whether HVPG-guided therapy is superior to standard combination therapy for the prevention of variceal bleeding in patients with decompensated cirrhosis.
- Conditions
- Liver Cirrhoses, Variceal Hemorrhage, Esophageal Varices
- Being tested
- Transjugular intrahepatic portosystemic shunt, Carvedilol, Endoscopic variceal ligation
- Keywords
- Transjugular intrahepatic portosystemic shunt, Endoscopic variceal ligation, Non-selective β-blocker therapy, Hepatic venous pressure gradient
- Medical subject headings
- Esophageal and Gastric Varices
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transjugular intrahepatic portosystemic shuntProcedure or surgery
The TIPS procedures will be performed by experienced interventional radiologists. polytetrafluroethylene-covered stents were used with initial balloon dilatation to 8 mm, aiming for a decrease in portal-venous pressure gradient to less than 12 mm Hg.
CarvedilolDrug
Carvedilol will be started at least 5 days after the index bleeding, unless a contraindication was present. Carvedilol will be start with 6.25 mg once a day and after 3 days increase to 6.25 mg twice-daily (the maximal dose was 12.5 mg/day). Systolic arterial blood pressure should not decrease <90 mmHg.
Endoscopic variceal ligationProcedure or surgery
For endoscopic variceal ligation, the first elective session will be carried out within 7 days of randomisation. Then EBL sessions were scheduled every 10-14 days until variceal eradication (disappearance of varices or being too small to be sucked in the banding device).
| Study group | Role | What they receive |
|---|---|---|
| HVPG-guided therapy | Experimental | HVPG will be determined before randomization. In this arm, patients with an adequate reduction in HVPG (responders) receive carvedilol whereas nonresponders receive TIPS. Receives: Procedure: Transjugular intrahepatic portosystemic shunt; Drug: Carvedilol |
| Standard therapy | Active comparator | In this group, both responders and nonresponders will receive combination therapy of carvedilol and endoscopic variceal ligation as first-line therapy. If first-line therapy fails, TIPS will considered. Receives: Drug: Carvedilol; Procedure: Endoscopic variceal ligation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of esophageal variceal rebleeding
Source of variceal rebleeding will be determined by endoscopy.
Measured: 12 months
Secondary outcomes (5)
Cumulative incidence of variceal rebleeding related death
Measured: 12 months
Cumulative incidence of all cause mortality
Measured: 12 months
Cumulative incidence of patients with further decompensation
Decompensation was defined as variceal rebleeding, ascites, and hepatic encephalopathy
Measured: 12 months
Cumulative incidence of patients with ascites
Measured: 12 months
Cumulative incidence of patients with hepatic encephalopathy
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start1 Jun 2020 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosesStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Air Force Military Medical University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tie Jun, Air Force Military Medical University, China
- Investigators
- Jun Tie, M.D.,Ph.D., Principal investigator, Air Force Military Medical University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04254822
- Sponsor's protocol ID
- KY20192149-F-1
- Status last verified
- Feb 2020
- First submitted
- 2 Feb 2020
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatic Vein Pressure Gradient(HVPG)-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Patients With Liver Cirrhosis: A Prospective Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04254822
- Acronym / sponsor ID
- KY20192149-F-1
- Conditions
- Liver Cirrhoses, Variceal Hemorrhage, Esophageal Varices
- Keywords
- Transjugular intrahepatic portosystemic shunt, Endoscopic variceal ligation, Non-selective β-blocker therapy, Hepatic venous pressure gradient
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Air Force Military Medical University, ChinaUniversity, hospital or other
- Study start
- 1 Jun 2020 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 5 Feb 2020 (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.
Variceal bleeding is a major complication of cirrhosis, associated with a hospital mortality rate of 10%-20%. Surviving patients are at high risk for recurrent hemorrhage. For these reasons, management should be directed at its prevention. Endoscopic variceal band ligation (EBL) in combination with non-selective β-blocker (NSBB) therapy is the recommended first line therapy. Transjugular intrahepatic portosystemic stent-shunt (TIPS) is the most effective method to prevent rebleeding, however, it is burdened with increased hepatic encephalopathy and deterioration of liver function in patients with advanced cirrhosis. So TIPS placement forms an alternative if first line therapy fails.
Hepatic venous pressure gradient (HVPG) is currently the best available method to evaluate the presence and severity of portal hypertension. Patients who experience a reduction in HVPG of ≥20% or to <12mmHg in response to drug therapy are defined as 'responders'. The lowest rebleeding rates are observed in patients on secondary prophylaxis who are HVPG responders. A recent meta-analysis has demonstrated that combination therapy is only marginally more effective than drug therapy. This suggests that pharmacological therapy is the cornerstone of combination therapy. Adding EBL may not be the optimal approach to improve the outcome of HVPG nonresponders and HVPG non-responders are a special high-risk population that may benefit from a more aggressive approach, such as an early decision for TIPS. It recently was shown that TIPS placement within 72 hours after acute bleeding not only prevented recurrent bleeding but also improved survival. These raise the question of whether ligation together with NSBB should remain the first choice for elective secondary prophylaxis.
Therefore, the purpose of the study is to compare whether HVPG-guided therapy is superior to standard combination therapy for the prevention of variceal bleeding in patients with decompensated cirrhosis.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HVPG-guided therapy | Experimental | Procedure: Transjugular intrahepatic portosystemic shunt, Drug: CarvedilolHVPG will be determined before randomization. In this arm, patients with an adequate reduction in HVPG (responders) receive carvedilol whereas nonresponders receive TIPS. |
| Standard therapy | Active comparator | Drug: Carvedilol, Procedure: Endoscopic variceal ligationIn this group, both responders and nonresponders will receive combination therapy of carvedilol and endoscopic variceal ligation as first-line therapy. If first-line therapy fails, TIPS will considered. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmed diagnosis of liver cirrhosis
- History of esophageal variceal bleeding confirmed by endoscopy
- Time interval between index bleeding and randomization > 5 days.
- Child-Pugh score < 12，MELD score<19
Key exclusion criteria (13 listed)
- Clinical manifestation of active bleeding
- Gastric variceal bleeding: GOV2，IGV1 or IGV2
- Degree of main portal vein thrombosis > 50%
- Refractory ascites
- Contraindications of TIPS
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 |
|---|---|---|
| Transjugular intrahepatic portosystemic shuntThe TIPS procedures will be performed by experienced interventional radiologists. polytetrafluroethylene-covered stents were used with initial balloon dilatation to 8 mm, aiming for a decrease in portal-venous pressure gradient to less than 12 mm Hg. | Procedure or surgery | HVPG-guided therapy |
| CarvedilolCarvedilol will be started at least 5 days after the index bleeding, unless a contraindication was present. Carvedilol will be start with 6.25 mg once a day and after 3 days increase to 6.25 mg twice-daily (the maximal dose was 12.5 mg/day). Systolic arterial blood pressure should not decrease <90 mmHg. | Drug | HVPG-guided therapy, Standard therapy |
| Endoscopic variceal ligationFor endoscopic variceal ligation, the first elective session will be carried out within 7 days of randomisation. Then EBL sessions were scheduled every 10-14 days until variceal eradication (disappearance of varices or being too small to be sucked in the banding device). | Procedure or surgery | Standard therapy |
Primary outcome
Cumulative incidence of esophageal variceal rebleeding
Time frame: 12 months
Source of variceal rebleeding will be determined by endoscopy.
5 secondary outcomes
Cumulative incidence of variceal rebleeding related death
Time frame: 12 months
Cumulative incidence of all cause mortality
Time frame: 12 months
Cumulative incidence of patients with further decompensation
Time frame: 12 months
Cumulative incidence of patients with ascites
Time frame: 12 months
Cumulative incidence of patients with hepatic encephalopathy
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Individual participant dataSharing planned: No
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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.
Jun Tie, M.D.,Ph.D. principal investigator
Air Force Military Medical University, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transjugular intrahepatic portosystemic shunt, Carvedilol and Endoscopic variceal ligation in people with Liver Cirrhoses and Variceal Hemorrhage, run by Air Force Military Medical University, China at 1 site in China.
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 13 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 5 Feb 2020. 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 China. 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 Jun Tie, M.D.,Ph.D. (+862984771537, tiejun7776@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative incidence of esophageal variceal rebleeding (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Feb 2020.