Carvedilol vs Band Ligation vs Combination Therapy for Primary Prophylaxis of Variceal Bleeding
| Status: | Withdrawn |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Gastrointestinal |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/26/2018 |
| Start Date: | July 2018 |
| End Date: | September 2021 |
A Phase 3 Study of Carvedilol vs Variceal Band Ligation vs Combination Therapy for Primary Prophylaxis of Variceal Bleeding
Subjects will be those individuals greater than 18 years of age with a diagnosis of cirrhosis
undergoing screening for esophageal varices. Eligible subjects will have a diagnosis of
cirrhosis and esophageal varices (graded as medium or large) with no prior history of
variceal bleeding. The diagnosis of cirrhosis will be based on clinical, radiologic, and/or
laboratory data. Patients will be randomly assigned using electronic medical records to one
of three treatment arms after screening esophagogastroduodenoscopy (EGD) has been performed
and large varices are identified. Primary outcome of the study will be the incidence of
variceal bleeding in patients receiving one of the following therapies for primary
prophylaxis of variceal bleeding: carvedilol, variceal band ligation (VBL), or both
carvedilol and VBL.
undergoing screening for esophageal varices. Eligible subjects will have a diagnosis of
cirrhosis and esophageal varices (graded as medium or large) with no prior history of
variceal bleeding. The diagnosis of cirrhosis will be based on clinical, radiologic, and/or
laboratory data. Patients will be randomly assigned using electronic medical records to one
of three treatment arms after screening esophagogastroduodenoscopy (EGD) has been performed
and large varices are identified. Primary outcome of the study will be the incidence of
variceal bleeding in patients receiving one of the following therapies for primary
prophylaxis of variceal bleeding: carvedilol, variceal band ligation (VBL), or both
carvedilol and VBL.
Inclusion criteria for the study will be an individual > 18 years old with a diagnosis of
cirrhosis (either by history, serology or imaging), with medium or large esophageal varices
on variceal screening esophagogastroduodenoscopy (EGD), and no prior history of
gastrointestinal (GI) bleeding, as related to portal hypertension. Exclusion criteria will be
the following: pregnant females; patients on beta blockers or nitrates for any underlying
condition; allergies to carvedilol; mean arterial pressure < 55 mm Hg or pulse < 55 beats per
minute at baseline; presence of hepatocellular carcinoma; presence of portal vein thrombosis;
patients with severe, uncontrolled respiratory disease (asthma, COPD); patients with complete
heart block or other significant arrhythmias; those with significant renal disease (CKD stage
III or higher); patients who are unable to provide consent; and patients who in the opinion
of the principal investigator are not suitable for participation in the trial.
Patients will be randomized to one of the following three treatment groups: (1) carvedilol
group, (2) variceal band ligation and (3) combination therapy (carvedilol plus variceal band
ligation). Since the standard of care at University Hospital is use of beta blocker
medications, the carvedilol group will serve as the control group.
After consent has been obtained for the EGD and research study and patients have met the
non-endoscopic inclusion and exclusion criteria mentioned above, they will undergo a
screening EGD to look for varices. Varices will be graded by the 2-group classification
system of "small" and "large". Varices are graded as large if > 5mm and small if < 5mm in
size. A biopsy forceps will be inserted through the biopsy channel of the gastroscope and
opened. An open biopsy forceps measures approximately 5mm in diameter. This will be used to
measure the size of the varices and will be confirmed by two physicians. If a patient is
found to have small esophageal varices, they will be excluded from the study and managed as
per the standard of care. Once a patient has been identified in having large esophageal
varices, he or she will undergo randomization during that initial endoscopy. A random number
generator will be used to randomize the patient into one of the three treatment groups
described above. If a patient is randomized to the carvedilol group, the endoscopic procedure
will be terminated and the patient will be given a prescription for carvedilol at the time of
discharge. He or she will then be followed up in our Gastroenterology clinics in a regular
fashion where medication can be titrated and symptoms can be assessed. If a patient is
randomized to the variceal band ligation group, the patient will undergo banding of the
esophageal varices with a Wilson-Cook multi-banding device. He/she will be started on a
proton-pump inhibitor post-procedure to minimize the risk of post-banding ulcers, a known
complication of variceal banding. Once the patient has been treated with VBL, this procedure
will be scheduled and repeated every two weeks until the obliteration of varices (ie once
varices cannot be detected on endoscopy). The first surveillance EGD after obliteration will
then be performed 1-3 months after obliteration and then every 6 months to check for variceal
recurrence. If a patient is randomized to the combination group, the patient will undergo the
banding protocol described above. The patient will then be given a prescription for
carvedilol and a proton-pump inhibitor on discharge and followed in our clinics as scheduled.
cirrhosis (either by history, serology or imaging), with medium or large esophageal varices
on variceal screening esophagogastroduodenoscopy (EGD), and no prior history of
gastrointestinal (GI) bleeding, as related to portal hypertension. Exclusion criteria will be
the following: pregnant females; patients on beta blockers or nitrates for any underlying
condition; allergies to carvedilol; mean arterial pressure < 55 mm Hg or pulse < 55 beats per
minute at baseline; presence of hepatocellular carcinoma; presence of portal vein thrombosis;
patients with severe, uncontrolled respiratory disease (asthma, COPD); patients with complete
heart block or other significant arrhythmias; those with significant renal disease (CKD stage
III or higher); patients who are unable to provide consent; and patients who in the opinion
of the principal investigator are not suitable for participation in the trial.
Patients will be randomized to one of the following three treatment groups: (1) carvedilol
group, (2) variceal band ligation and (3) combination therapy (carvedilol plus variceal band
ligation). Since the standard of care at University Hospital is use of beta blocker
medications, the carvedilol group will serve as the control group.
After consent has been obtained for the EGD and research study and patients have met the
non-endoscopic inclusion and exclusion criteria mentioned above, they will undergo a
screening EGD to look for varices. Varices will be graded by the 2-group classification
system of "small" and "large". Varices are graded as large if > 5mm and small if < 5mm in
size. A biopsy forceps will be inserted through the biopsy channel of the gastroscope and
opened. An open biopsy forceps measures approximately 5mm in diameter. This will be used to
measure the size of the varices and will be confirmed by two physicians. If a patient is
found to have small esophageal varices, they will be excluded from the study and managed as
per the standard of care. Once a patient has been identified in having large esophageal
varices, he or she will undergo randomization during that initial endoscopy. A random number
generator will be used to randomize the patient into one of the three treatment groups
described above. If a patient is randomized to the carvedilol group, the endoscopic procedure
will be terminated and the patient will be given a prescription for carvedilol at the time of
discharge. He or she will then be followed up in our Gastroenterology clinics in a regular
fashion where medication can be titrated and symptoms can be assessed. If a patient is
randomized to the variceal band ligation group, the patient will undergo banding of the
esophageal varices with a Wilson-Cook multi-banding device. He/she will be started on a
proton-pump inhibitor post-procedure to minimize the risk of post-banding ulcers, a known
complication of variceal banding. Once the patient has been treated with VBL, this procedure
will be scheduled and repeated every two weeks until the obliteration of varices (ie once
varices cannot be detected on endoscopy). The first surveillance EGD after obliteration will
then be performed 1-3 months after obliteration and then every 6 months to check for variceal
recurrence. If a patient is randomized to the combination group, the patient will undergo the
banding protocol described above. The patient will then be given a prescription for
carvedilol and a proton-pump inhibitor on discharge and followed in our clinics as scheduled.
Inclusion Criteria:
- Inclusion criteria for the study will be an individual > 18 years old with a diagnosis
of cirrhosis (either by history, serology or imaging), with medium or large esophageal
varices on variceal screening esophagogastroduodenoscopy (EGD), and no prior history
of gastrointestinal (GI) bleeding, as related to portal hypertension
Exclusion Criteria:
- Exclusion criteria will be the following: pregnant females; patients on beta blockers
or nitrates for any underlying condition; allergies to carvedilol; mean arterial
pressure < 55 mm Hg or pulse < 55 beats per minute at baseline; presence of
hepatocellular carcinoma; presence of portal vein thrombosis; patients with severe,
uncontrolled respiratory disease (asthma, COPD); patients with complete heart block or
other significant arrhythmias; those with significant renal disease (CKD stage III or
higher); patients who are unable to provide consent; and patients who in the opinion
of the principal investigator are not suitable for participation in the trial.
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