Clinical trial NCT04254822: HVPG-Guided Therapy vs Carvedilol Plus Endotherapy for the Prevention of Esophageal Variceal Rebleeding in Cirrhotic Patients
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Cirrhoses
Variceal Hemorrhage
Esophageal Varices
Keywords: Transjugular intrahepatic portosystemic shunt
Endoscopic variceal ligation
Non-selective β-blocker therapy
Hepatic venous pressure gradient
Lead sponsor: Air Force Military Medical University, China
Sponsor class: OTHER
First posted: 2020-02-05
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Cumulative incidence of esophageal variceal rebleeding
timeFrame: 12 months
Secondary outcomes:
measure: Cumulative incidence of variceal rebleeding related death
timeFrame: 12 months
measure: Cumulative incidence of all cause mortality
timeFrame: 12 months
measure: Cumulative incidence of patients with further decompensation
timeFrame: 12 months
measure: Cumulative incidence of patients with ascites
timeFrame: 12 months
measure: Cumulative incidence of patients with hepatic encephalopathy
timeFrame: 12 months
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Fourth Military Medical University
state: Shaanxi
Study officials:
affiliation: Air Force Military Medical University, China
name: Jun Tie, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: