Esophageal and Gastric VaricesPhase 4NCT02504723
Carvedilol as an Adjunct to Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding
A Phase 4 study testing carvedilol and cyanoacrylate in people with Esophageal and Gastric Varices, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.
Trial summary
Gastric variceal obturation is the current endoscopic therapy of choice for gastric variceal bleeding but is associated with a high rebleeding rate. Carvedilol is a potent non-selective β-blocker. The role of carvedilol in the prevention of recurrent gastric variceal bleeding is not studied. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Esophageal and Gastric Varices
- What is being tested?
- carvedilol and cyanoacrylate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 1 siteTaiwan
- Study dates
- Dec 2011to Feb 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age of 20 to 80 years
- Cirrhotic patients with acute gastric variceal bleeding proven by an endoscopy within 24 h of bleeding
- Stable hemodynamic condition for at least 3 days after cyanoacrylate injection
Who cannot join
- Previous treatment of gastric varices, including endoscopic therapy, transjugular intrahepatic porto-systemic shunt, or surgery
- Contraindications to non-selective beta-blockers or cyanoacrylate injection
- Serum total bilirubin >10 mg/dL
- Grade III/IV hepatic encephalopathy
- Hepato-renal syndrome
- Severe heart failure (NYHA Fc III/IV)
Show all 12Show fewer
- Chronic kidney disease under renal replacement therapy
- Refractory ascites
- Malignancy other than hepatocellular carcinoma
- Pregnancy
- Pacemaker use
- Refusal to participate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Carvedilol Plus Endoscopic Cyanoacrylate Injection Versus Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding
Gastric variceal obturation is the current endoscopic therapy of choice for gastric variceal bleeding but is associated with a high rebleeding rate. Carvedilol is a potent non-selective β-blocker. The role of carvedilol in the prevention of recurrent gastric variceal bleeding is not studied. This study aimed at evaluating the efficacy of carvedilol as an adjunct to gastric variceal obturation in the secondary prophylaxis of gastric variceal bleeding.
Read the detailed description
Gastric variceal bleeding is a lethal complication of portal hypertension. The rebleeding rate ranged between 30% to 50% in patients after initial hemostasis. Endoscopic cyanoacrylate injection is currently the choice of endoscopic therapy of acute gastric variceal bleeding and prevention of recurrent bleeding. However, the rebleeding rate is still high in the patients undergoing repeated endoscopic cyanoacrylate injection.
Non-selective β-blockers are frequently used for the secondary prophylaxis of variceal bleeding. In the case of esophageal varices, combination of non-selective β-blockers and endoscopic therapy significantly lowers the rebleeding rate compared with endoscopic therapy alone. However, propranolol failed to decrease the rebleeding rate as an adjunct to endoscopic cyanoacrylate injection and was associated with a higher incidence of adverse effects in gastric variceal bleeding patients. A more potent non-selective β-blocker than propranolol might further decrease portal pressure and decrease the rebleeding rate.
Carvedilol is a potent non-selective β-blocker with both beta and alpha-1 blocker effect. It significantly lowers portal pressure even in propranolol non-responders. However, it is unclear weather carvedilol will play a role in the prevention of recurrent gastric variceal bleeding. The investigators conducted a randomized controlled trial to compare the efficacy of carvedilol combined with endoscopic cyanoacrylate injection with endoscopic cyanoacrylate injection alone in secondary prophylaxis of gastric variceal bleeding.
- Conditions
- Esophageal and Gastric Varices
- Being tested
- carvedilol, cyanoacrylate
- Keywords
- Gastric varices, cyanoacrylate, carvedilol
- 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.
carvedilolDrug
Oral carvedilol is started after randomization at an initial dose of 6.25 mg daily. Doses are increased every 3 days during the admission or every 7 days in the out-patient clinics until the maximum tolerated dose was achieved or up to 25 mg daily, aiming at reducing resting pulse rate by 25 percent but not below 55 beats per minute with systolic blood pressure >90 mm Hg.
cyanoacrylateDrug
The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.
| Study group | Role | What they receive |
|---|---|---|
| Cyanoacrylate injection plus carvedilol | Experimental | The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. Oral carvedilol is administrated during the whole study period, starting at 6.25 mg daily and increased until the maximum tolerated dose. Receives: Drug: carvedilol; Drug: cyanoacrylate |
| Cyanoacrylate injection | Active comparator | The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. Receives: Drug: cyanoacrylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rebleeding From Gastric Varices
Rebleeding from gastric varices during the follow-up period
Measured: Within 6 years
Secondary outcomes (3)
All Upper Gastrointestinal Bleeding
All upper gastrointestinal bleeding during the follow-up period
Measured: Within 6 years
All Cause Mortality or Liver Transplantation
All cause mortality or liver transplantation during the study period
Measured: Within 6 years
All Adverse Effects
All adverse effects during the study period
Measured: Within 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study startDec 2011
- Primary completionFeb 2017
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Esophageal and Gastric VaricesStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kaohsiung Veterans General Hospital.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wen-Chi Chen, Kaohsiung Veterans General Hospital.
- Investigators
- Wen-Chi Chen, MD, Principal investigator, Kaohsiung Veterans General Hospital.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02504723
- Sponsor's protocol ID
- VGHKS11-CT10-11
- Status last verified
- Jul 2017
- First submitted
- 18 Jul 2015
- Last updated
- 21 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen WC, Hsin IF, Chen PH, Hsu PI, Wang YP, Cheng JS, Lin HS, Hou MC, Lee FY. Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2019 Oct;17(11):2356-2363.e2. doi: 10.1016/j.cgh.2019.02.021. Epub 2019 Feb 14.
PubMed 30772583
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carvedilol Plus Endoscopic Cyanoacrylate Injection Versus Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding
- ClinicalTrials.gov ID
- NCT02504723
- Acronym / sponsor ID
- VGHKS11-CT10-11
- Conditions
- Esophageal and Gastric Varices
- Keywords
- Gastric varices, cyanoacrylate, carvedilol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Kaohsiung Veterans General Hospital.University, hospital or other
- Study start
- Dec 2011 (actual)
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 22 Jul 2015 (estimated)
- Results
- Posted 27 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Gastric variceal obturation is the current endoscopic therapy of choice for gastric variceal bleeding but is associated with a high rebleeding rate. Carvedilol is a potent non-selective β-blocker. The role of carvedilol in the prevention of recurrent gastric variceal bleeding is not studied. This study aimed at evaluating the efficacy of carvedilol as an adjunct to gastric variceal obturation in the secondary prophylaxis of gastric variceal bleeding.
Detailed description
Gastric variceal bleeding is a lethal complication of portal hypertension. The rebleeding rate ranged between 30% to 50% in patients after initial hemostasis. Endoscopic cyanoacrylate injection is currently the choice of endoscopic therapy of acute gastric variceal bleeding and prevention of recurrent bleeding. However, the rebleeding rate is still high in the patients undergoing repeated endoscopic cyanoacrylate injection.
Non-selective β-blockers are frequently used for the secondary prophylaxis of variceal bleeding. In the case of esophageal varices, combination of non-selective β-blockers and endoscopic therapy significantly lowers the rebleeding rate compared with endoscopic therapy alone. However, propranolol failed to decrease the rebleeding rate as an adjunct to endoscopic cyanoacrylate injection and was associated with a higher incidence of adverse effects in gastric variceal bleeding patients. A more potent non-selective β-blocker than propranolol might further decrease portal pressure and decrease the rebleeding rate.
Carvedilol is a potent non-selective β-blocker with both beta and alpha-1 blocker effect. It significantly lowers portal pressure even in propranolol non-responders. However, it is unclear weather carvedilol will play a role in the prevention of recurrent gastric variceal bleeding. The investigators conducted a randomized controlled trial to compare the efficacy of carvedilol combined with endoscopic cyanoacrylate injection with endoscopic cyanoacrylate injection alone in secondary prophylaxis of gastric variceal bleeding.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyanoacrylate injection plus carvedilol | Experimental | Drug: carvedilol, Drug: cyanoacrylateThe patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. Oral carvedilol is administrated during the whole study period, starting at 6.25 mg daily and increased until the maximum tolerated dose. |
| Cyanoacrylate injection | Active comparator | Drug: cyanoacrylateThe patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age of 20 to 80 years
- Cirrhotic patients with acute gastric variceal bleeding proven by an endoscopy within 24 h of bleeding
- Stable hemodynamic condition for at least 3 days after cyanoacrylate injection
Key exclusion criteria (12 listed)
- Previous treatment of gastric varices, including endoscopic therapy, transjugular intrahepatic porto-systemic shunt, or surgery
- Contraindications to non-selective beta-blockers or cyanoacrylate injection
- Serum total bilirubin >10 mg/dL
- Grade III/IV hepatic encephalopathy
- Hepato-renal syndrome
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 |
|---|---|---|
| carvedilolOral carvedilol is started after randomization at an initial dose of 6.25 mg daily. Doses are increased every 3 days during the admission or every 7 days in the out-patient clinics until the maximum tolerated dose was achieved or up to 25 mg daily, aiming at reducing resting pulse rate by 25 percent but not below 55 beats per minute with systolic blood pressure >90 mm Hg. | Drug | Cyanoacrylate injection plus carvedilol |
| cyanoacrylateThe patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. | Drug | Cyanoacrylate injection, Cyanoacrylate injection plus carvedilol |
Primary outcome
Rebleeding From Gastric Varices
Time frame: Within 6 years
Rebleeding from gastric varices during the follow-up period
3 secondary outcomes
All Upper Gastrointestinal Bleeding
Time frame: Within 6 years
All Cause Mortality or Liver Transplantation
Time frame: Within 6 years
All Adverse Effects
Time frame: Within 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30772583Chen WC, Hsin IF, Chen PH, Hsu PI, Wang YP, Cheng JS, Lin HS, Hou MC, Lee FY. Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2019 Oct;17(11):2356-2363.e2. doi: 10.1016/j.cgh.2019.02.021. Epub 2019 Feb 14.
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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.
Wen-Chi Chen, MD principal investigator
Kaohsiung Veterans General Hospital.
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 carvedilol and cyanoacrylate in people with Esophageal and Gastric Varices, run by Kaohsiung Veterans General Hospital. 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 3 inclusion and 12 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: finished, as of the sponsor's last update on 21 Aug 2017. 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. 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?
Yes. Results are posted in the registry (first posted 27 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rebleeding From Gastric Varices (time frame: Within 6 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 NCT02504723, 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 21 Aug 2017.