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

Air Force Military Medical University of People's Liberation Army

Status: Unknown

Conditions: Liver Cirrhoses; Esophageal Varices; Variceal Hemorrhage

Treatments: Drug: Carvedilol; Procedure: Transjugular intrahepatic portosystemic shunt; Procedure: Endoscopic variceal ligation

Study type: Interventional

Funder types: Other

Identifiers

NCT04254822

KY20192149-F-1

Details and patient eligibility

About

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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 2 patient groups

HVPG-guided therapy

Experimental group

Description:

HVPG will be determined before randomization. In this arm, patients with an adequate reduction in HVPG (responders) receive carvedilol whereas nonresponders receive TIPS.

Treatment:

Procedure: Transjugular intrahepatic portosystemic shunt

Drug: Carvedilol

Standard therapy

Active Comparator group

Description:

In this group, both responders and nonresponders will receive combination therapy of carvedilol and endoscopic variceal ligation as first-line therapy. If first-line therapy fails, TIPS will considered.

Treatment:

Procedure: Endoscopic variceal ligation

Drug: Carvedilol