The Effect of Hepatic Vein Pressure Gradient(HVPG)-Guided Therapy in Cirrhotic Patients With Esophagogastric Varices

Study Overview
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Brief Summary
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The purpose of the study is to compare the effect of HVPG-guided individualized therapy and non-HVPG guided traditional therapy in cirrhotic patients for secondary prophylaxis.

Detailed Description
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The study is a randomized controlled trial of Zelen-design. Patients randomly enter two treatment groups: 1) the HVPG group and 2) the non-HVPG group. Treatment allocation is by block randomization with an equal number for both groups. The results are concealed in opaque envelopes.After randomization, patients will have a second chance to decide if they want to stay in the current group.Patients can switch to another group according to their will. If they are in the HVPG group，they will receive HVPG measurement before treatment. If they are in the non-HVPG group, they start treatment without HVPG measurement and receive endoscopic treatment plus Carvedilol.The mortality rate and rebleeding rate will be analyzed.

Official Title
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The Effect of HVPG-Guided Individualized Therapy in Patients With Cirrhosis Related Esophagogastric Variceal Hemorrhage For Secondary Prophylaxis:A Randomized Controlled Trial

Conditions
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Gastroesophageal Varices, Cirrhosis

Intervention / Treatment
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* Procedure: HVPG-guided therapy
* Other: routine therapy
* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cirrhosis diagnosed by histology, radiological evidence of cirrhosis, and endoscopic evidence of varices; Patients with a previous history of variceal hemorrhage; Patients admitted to Zhongshan Hospital and other 6 tertiary centers in Shanghai from Dec 1, 2015 to Sep 31,2018 Exclusion Criteria: Patients already taken secondary prophylactic treatment including endoscopic, pharmacological, surgical and interventional therapies; Patients with severe systemic diseases such as chronic heart failure or chronic renal failure that will have impact on survival; Patients in pregnancy and lactation; Patients already diagnosed with hepatic cellular carcinoma or other malignant tumors; Patients with contraindication to treatment of endoscopy, surgery and TIPS: severe coagulation defects, allergic to contrast medium used in TIPS, hepatic encephalopathy, spontaneous bacterial peritonitis; Patients with conditions that will influence the accuracy of HVPG measurement: Cavernous transformation of portal vein, diffused portal vein thrombosis, severe shunt; Patients refuse to give consent to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HVPG group<br>HVPG-guided therapy | Procedure: HVPG-guided therapy<br>* Patients with an HVPG over 20mmHg will be suggested to receive transjugular intrahepatic portocaval shunt (TIPS) or surgical shunt operation. Patients with an HVPG between 16 and 20mmHg can choose either endoscopic treatment or TIPS according their willingness and indication. Patients with an HVPG below 16mmHg will be treated by endoscopy plus Carvedilol, until endoscopic treatment fails.<br>Drug: Carvedilol<br>* Patients in HVPG group with HVPG below 16mmHg and all patients in non-HVPG group will take Carvedilol 12.5mg/d if they have no contraindications.<br>|
| Other: non-HVPG group<br>routine therapy | Other: routine therapy<br>* Patients start treatment without HVPG measurement and receive endoscopic therapy plus Carvedilol.<br>Drug: Carvedilol<br>* Patients in HVPG group with HVPG below 16mmHg and all patients in non-HVPG group will take Carvedilol 12.5mg/d if they have no contraindications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | The investigators observe the mortality events in both groups during the study | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rebleeding rate | The investigators observe the rebleeding events in both groups during the study | through study completion, an average of 1 year | 
| Adverse Events | The investigators observe any severe adverse events caused by HVPG measurement, endoscopic procedures,use of Carvedilol, surgical operations or TIPS | through study completion, an average of 1 year | 
| Total cost | The investigators calculate the total cost of treatment of each patient during the study | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HVPG