HVPG-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Cirrhotic Patients

Liver Cirrhoses Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04254822
• Other study ID #: KY20192149-F-1
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2020
• Source: Fourth Military Medical University
• Contact: Jun Tie, M.D.,Ph.D.
• Phone: +862984771537
• Email: tiejun7776[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 220
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Budd-Chiari Syndrome

• Malignancy tumor

• Uncontrolled infections

• History of portal-systemic shunt surgery

• HIV

• Pregnancy or breastfeeding woman

• Poor incompliance

Related Conditions & MeSH terms

• Esophageal and Gastric Varices
• Esophageal Varices
• Fibrosis
• Hemorrhage
• Liver Cirrhoses
• Liver Cirrhosis
• Variceal Hemorrhage

Intervention

Procedure:
• Transjugular intrahepatic portosystemic shunt
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.

Drug:
• Carvedilol
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.

Procedure:
• Endoscopic variceal ligation
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).

Locations

Country	Name	City	State
China	Fourth Military Medical University	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Fourth Military Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of esophageal variceal rebleeding	Source of variceal rebleeding will be determined by endoscopy.	12 months
Secondary	Cumulative incidence of variceal rebleeding related death		12 months
Secondary	Cumulative incidence of all cause mortality		12 months
Secondary	Cumulative incidence of patients with further decompensation	Decompensation was defined as variceal rebleeding, ascites, and hepatic encephalopathy	12 months
Secondary	Cumulative incidence of patients with ascites		12 months
Secondary	Cumulative incidence of patients with hepatic encephalopathy		12 months