Impact of Nonselective Beta-blocker on Acute Kidney Injury in Cirrhotic Patients With Esophageal Varices (AKI)

Taipei Veterans General Hospital

Status and phase: Unknown; Phase 4

Conditions: Esophageal Varices; Cirrhosis; Acute Kidney Injury

Treatments: Procedure: Esophageal varice ligation; Other: DC propranolol; Drug: propranolol

Study type: Interventional

Funder types: Other

Identifiers

NCT04074473

2015-04-014A

Details and patient eligibility

About

We will include patients with EV and EVB. They will be randomized to EVL vs. NSBB for primary prevention And EVL+long-term NSBB vs. EVL+short-term NSBB for secondary prevention. 150 patients will be included in a 3-year period. Primary end-points are formation/progression of ascites, acute kidney injury and survival. The other outcomes such as bleeding, rebleeding, infection and other risk factors will be also analyzed.

Full description

Despite advance in the prevention and treatment of esophageal variceal bleeding (EVB), it is still a majorcomplication of portal hypertension with the characteristic of a high mortality around 15~20% after anepisode of hemorrhage. Following development of EV and EVB, ascites and renal dysfunction occurs in a large portion of patients with time. The international consensus suggested use of non-selective beta-blocker(NSBB) to prevent EVB. Long-term use of NSBB was also found to decrease occurrence of encephalopathy and spontaneous bacterial peritonitis (SBP) and extend survival. Until 2010, Dr. Lebrec et al. found use of NSBB might decrease survival in cirrhotic patients with refractory ascites, therefore they suggested discontinued use of NSBB in these patients. The findings lead to a vigorous dispute between hepatologists. In 2011, the reputable team again found use of NSBB might cause post-paracentesis circulatory dysfunction (PPCD) in cirrhotic patients undergoing a large volume paracentesis. Occurrence of PPCD was known to cause acute kidney injury (AKI) and increase mortality. In 2014, Austria investigators found use of NSBB was associated with increased AKI and shortened survival in patients with SBP. Despite the findings of these studies implicated the harmful aspects of NSBB use, a major debate remained because lack of randomized controlled trial some unequal distribution of patients.Taipei Veterans General Hospital is renowned by its high profile research in portal hypertension and its related complications. The current proposal is aimed to clarify the strategy of NSBB use. We will include patients with EV and EVB. They will be randomized to EVL vs. NSBB for primary prevention And EVL+long-term NSBB vs. EVL+short-term NSBB for secondary prevention. 150 patients will be included in a 3-year period. Primary end-points are formation/progression of ascites, acute kidney injury and survival. The other outcomes such as bleeding, rebleeding, infection and other risk factors will be also analyzed.

Enrollment: 170 estimated patients

Sex: All

Ages: 20 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Criteria

Inclusion Criteria:

Age of 20 to 85 years

Cirrhotic patients with esophageal varices regardless of bleeding event or not will be enrolled in this study.

Exclusion Criteria:

Terminal stage HCC/ other malignancy/ Stroke or active sepsis/ Chronic kidney disease stage 4 under renal replacement therapy/ Contraindications to non-selective beta-blockers/ A history of non-selective beta-blockers use, sclerotherapy, banding ligation, transjugular intrahepatic porto-systemic shunt, or shunt surgery/ Serum total bilirubin >10 mg/dL/ Refractory ascites/ Hepato-renal syndrome/ Pregnancy/ Severe heart failure (NYHA Fc III/IV)/ Bronchial asthma or chronic obstructive pulmonary disease/ Second or third degree atrioventricular block/ Severe hypotension/ Refusal to participate

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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170 participants in 4 patient groups, including a placebo group

Propranolol alone

Placebo Comparator group

Description:

TPropranolol 10mg BID initially and titrate dosage every week to achieve 25% drop of heart rate (keep heart rate\>55 or systemic blood pressure\>90mmHg)

Treatment:

Drug: propranolol

Esophageal variceal ligation alone

Active Comparator group

Description:

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.

Treatment:

Procedure: Esophageal varice ligation

Esophageal variceal ligation(DC inderal after EV eradication)

Experimental group

Description:

Patients randomized to banding ligation group discontinue propranolol after eradication of esophageal varices.

Treatment:

Other: DC propranolol

Propranolol(Keep BB after EV eradication)

No Intervention group

Description:

Patients randomized to propranolol group continue propranolol after eradication of esophageal varices.