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

NCT04254822 | Unknown

• 1 other identifier: KY20192149-F-1
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cirrhoses; Variceal Hemorrhage; Esophageal Varices

Keywords

Transjugular intrahepatic portosystemic shunt; Endoscopic variceal ligation; Non-selective β-blocker therapy; Hepatic venous pressure gradient

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of esophageal variceal rebleeding

  Source of variceal rebleeding will be determined by endoscopy.

  12 months

Secondary Outcomes (5)

• Cumulative incidence of variceal rebleeding related death

  12 months

• Cumulative incidence of all cause mortality

  12 months

• Cumulative incidence of patients with further decompensation

  12 months

• Cumulative incidence of patients with ascites

  12 months

• Cumulative incidence of patients with hepatic encephalopathy

  12 months

Study Arms (2)

HVPG-guided therapy

EXPERIMENTAL

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

Procedure: Transjugular intrahepatic portosystemic shunt; Drug: Carvedilol

Standard therapy

ACTIVE COMPARATOR

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.

Drug: Carvedilol; Procedure: Endoscopic variceal ligation

Interventions

Transjugular intrahepatic portosystemic shunt PROCEDURE

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.

HVPG-guided therapy

Carvedilol DRUG

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.

HVPG-guided therapy; Standard therapy

Endoscopic variceal ligation PROCEDURE

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).

Standard therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (1)

Fourth Military Medical University

Xi'an, Shaanxi, 710032, China

Location

MeSH Terms

Conditions

Esophageal and Gastric Varices

Interventions

Portasystemic Shunt, Transjugular Intrahepatic; Carvedilol

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Hypertension, Portal; Liver Diseases

Intervention Hierarchy (Ancestors)

Portasystemic Shunt, Surgical; Anastomosis, Surgical; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Jun Tie, M.D.,Ph.D.

  Air Force Military Medical University, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Tie, M.D.,Ph.D.

CONTACT

+862984771537; tiejun7776@163.com

Hui Chen, M.D.,Ph.D.

CONTACT

+862984771537; qychenhui@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary investigator

Study Record Dates

• First Submitted: February 2, 2020
• First Posted: February 5, 2020
• Study Start: June 1, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: February 5, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)