Clinical trial NCT01809535: Monthly Versus Biweekly Endoscopic Variceal Ligation for the Prevention of Esophageal Variceal Rebleeding
Official title: A Randomized Controlled Trial of Monthly Versus Biweekly Endoscopic Variceal Ligation for the Prevention of Esophageal Variceal Rebleeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Variceal Bleeding, Endoscopic Variceal Ligation
Keywords: endoscopic variceal ligation
post-EVL ulcer
variceal bleeding
Lead sponsor: Kaohsiung Veterans General Hospital.
Sponsor class: OTHER
Collaborators: name: Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
name: National Yang-Ming University, Kaohsiung, Taiwan, ROC
First posted: 2013-03-12
Enrollment: 70
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Endoscopic variceal ligation (EVL) has proved to be effective in the prevention of esophageal variceal rebleeding. However, the optimal interval of EVL remains unclear. Our previous studies demonstrated that repeating EVL every 3-4 weeks could achieve an appreciable low incidence of variceal rebleeding and mortality. In our own opinion, many shallow post-EVL ulcers may hamper the performance of variceal ligation if EVL is performed at intervals of 1-2 weeks. So far the optimal treatment interval remained unknown. The investigators hypothesis the Monthly EVL is superior to the Biweekly EVL in the prevention of esophageal variceal rebleeding in cirrhotic patients.

Detailed description: Esophageal varices are the most important portosystemic collaterals owing to their rupture results in variceal hemorrhage, which is a devastating event of portal hypertension. Cirrhotic patients surviving a first episode of variceal rupture have a risk of over 60% of suffering from recurrent bleeding within 1 year and mortality from each rebleeding episode is about 20%. Except for patients with a terminal illness, the secondary preventive measures are required to reduce variceal rebleeding to improve patient survival and clinical outcome. Endoscopic and pharmacological therapies are 2 main methods of intervention used to achieve the treatment goals. Endoscopic therapy contains endoscopic injection sclerotherapy (EIS) or endoscopic variceal ligation (EVL), which would obliterate varices by causing thrombosis and fibrosis formation. However, EVL has currently replaced EIS as the endoscopic therapy of choice because it is safer, more effective, and has lower morbidity rate.

Many experts and scholars suggest to repeat EVL every 1-2 weeks until obliteration of esophageal varices to prevent variceal rebleeding, whereas, there are insufficient data to support the concept that EVL at intervals of 1-2 week is appropriate. Our previous studies demonstrated that repeating EVL every 3-4 weeks could achieve an appreciable low incidence of variceal rebleeding and mortality. In our own opinion, many shallow post-EVL ulcers may hamper the performance of variceal ligation if EVL is performed at intervals of 1-2 weeks. A randomized controlled trial from Japan showed that EVL performed at a bimonthly interval obtained a higher variceal obliteration rate, lower variceal recurrence rate and fewer additional treatments. Bimonthly EVL in the secondary prophylaxis of variceal hemorrhage may be theoretically improper because post-EVL variceal rebleeding could only be significantly reduced in whom variceal obliteration was achieved within a short treatment course. The other retrospective investigation from the United States demonstrated the principal technical aspects of EVL in the prevention of variceal rebleeding, suggesting the benefit of intersession intervals \> 3 weeks compared with intervals \< 3 weeks.

This randomized controlled study was undertaken to compare the effectiveness and safety of EVL with two different intersession intervals (bimonthly vs. biweekly). In addition, the risk factors that were associated with variceal rebleeding and mortality were analyzed.

Eligibility criteria: Inclusion Criteria:

* active or recent hemorrhage from esophageal varices;
* portal hypertension caused by cirrhosis

Exclusion Criteria:

* age \> 80 or \<20 years old
* association with hepatocellular carcinoma or other neoplasms;
* association with cerebral vascular accident, uremia, acute coronary syndrome or other severe illnesses;
* history of gastric variceal bleeding;
* a history of undergoing EIS, EVL, cyanoacrylate injection or prior use of beta blocker;
* a history of prior shunt operation or transjugular intrahepatic portosystemic stent shunt (TIPS);
* deep jaundice (serum bilirubin \> 10 mg/dL);
* encephalopathy equal to or greater than stage II;
* failure in control of index variceal bleeding;
* death within 48 h of admission; or
* refusal to participate in the trial.

Primary outcomes:
measure: Rebleeding
timeFrame: From date of randomization until the date of first documented rebleeding, or date of death from any cause, or date of study closure, whichever came first, assessed up to 46 months
Secondary outcomes:
measure: Variceal recurrence
timeFrame: From date of variceal obliteration until the date of first documented variceal recurrence, or date of death from any cause, or date of study closure, whichever came first, assessed up to 46 months
measure: All-cause death
timeFrame: From date of randomization until the date of death from any cause, or date of study closure, whichever came first, assessed up to 46 months
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
Study officials:
affiliation: Kaohsiung Veterans General Hospital.
name: Huay-Min Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaohsiung Veterans General Hospital.
name: Ping-I Hsu, MD
role: STUDY_DIRECTOR
affiliation: E-DA Hospital, Kaohsiung, Taiwan
name: Gin-Ho Lo, MD
role: STUDY_DIRECTOR
References:
citation: Wang HM, Lo GH, Chen WC, Chan HH, Tsai WL, Yu HC, Tsay FW, Hsu PI. Randomized controlled trial of monthly versus biweekly endoscopic variceal ligation for the prevention of esophageal variceal rebleeding. J Gastroenterol Hepatol. 2014 Jun;29(6):1229-36. doi: 10.1111/jgh.12538.