Cirrhosis
Conditions
Keywords
cirrhosis, propranolol, decompensation, recompensation, survival, MELD
Brief summary
Non selective beta blockers (NSBBs), such as propranolol and nadolol, are mainstay therapies for portal hypertension in cirrhosis, but their efficacy and safety vary depending on the stage of the disease. Emerging evidence suggests that NSBBs may worsen the prognosis of advanced cirrhosis, especially in patients with a model for end-stage liver disease (MELD) score of \>9. The purpose of this randomized controlled trial is to evaluate the effects of the use of propranolol as recommended by the guideline on the prognosis in cirrhotic patients with a MELD score of \>9.
Detailed description
This is a non-inferiority, randomized controlled trial. A total of 466 decompensated cirrhotic patients with a MELD score of \>9 will be enrolled. Participants will be stratified based on the presence or absence of acute decompensation at enrollment, and then randomly assigned at a 1:1 ratio to conventional treatment combined with or without propranolol groups. All patients will receive standard medical therapy in both groups, and then regularly followed. The primary outcome is further decompensation. The secondary outcomes include recompensation and death.
Interventions
OTHERconventional therapy
Conventional treatment of decompensated cirrhosis mainly includes anti-hepatic fibrosis drugs, albumin infusion, diuretics, peritoneal drainage, esophageal variceal ligation, endoscopic tissue adhesive injection, blood purification, and liver transplantation.
DRUGpropranolol
Propranolol will be started with 10-20 mg/day for the propranolol group, which will be gradually increased to the maximum tolerance dosage or achieve a heart rate of 55-60 beats per minute and a systolic blood pressure of 90mmHg.
Sponsors
General Hospital of Shenyang Military Region
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients' age ≥18 years; * patients with a definitive diagnosis of liver cirrhosis; * patients with a MELD score of \>9; * patients with a history of decompensation or those who are experiencing their first decompensation, such as ascites, variceal bleeding, or hepatic encephalopathy (HE); * patients' informed consents.
Exclusion criteria
* patients without a definite indication for NSBBs; * patients with an absolute contraindication of NSBBs (severe bronchospasm, asthma, severe psychosis, high-degree atrioventricular block, etc.); * patients with hypersensitivity to NSBBs; * patients who had been treated with NSBBs before 2 weeks of enrollment; * patients with occlusive portal vein thrombosis; * patients who had undergone liver transplantation; * patients who had undergone transjugular intrahepatic portosystemic shunt (TIPS); * patients with a definitive diagnosis of hepatocellular carcinoma; * patients with an estimated life time of \<12 months due to the presence of any comorbidities; * patients who are currently pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The time from randomization to the occurrence of further decompensation | Time to first further decompensation event, assessed from randomization up to the end of the study (maximum of approximately 96 weeks) | Further decompensation is defined as any of the following conditions: 1. the occurrence of a second portal hypertension driven decompensation event (ascites, variceal bleeding or HE) and/or non-obstructive jaundice; 2. the occurrence of recurrent variceal bleeding, refractory ascites, recurrent HE, SBP, and/or HRS-AKI; 3. the occurrence of ascites, HE, or jaundice in patients with bleeding alone after recovery from bleeding, according to the Baveno VII consensus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The time from randomization to the occurrence of recompensation | Time to first recompensation event, assessed from randomization up to the end of the study (maximum of approximately 96 weeks) | Recompensation is defined as all of the following criteria are met: 1. removal/suppression/cure of the primary cause of cirrhosis (e.g., removal of hepatitis C virus, sustained suppression of hepatitis B virus, or sustained alcohol abstinence in alcoholic cirrhosis); 2. resolution of ascites in the setting of discontinuation of diuretics, absence of HE in the setting of discontinuation of lactulose/rifaximin, and absence of recurrent variceal bleeding within at least 12 months; 3. stable improvement of liver function (e.g., albumin, international normalized ratio, bilirubin) |
| The time from randomization to the occurrence of death | assessed from randomization up to the end of the study (maximum of approximately 96 weeks) | All-cause mortality during the study period |
| The composite endpoint of further decompensation and death | assessed from randomization up to the end of the study (maximum of approximately 96 weeks) | — |
| The hierarchical composite endpoint of death and further decompensation | assessed from randomization up to the end of the study (maximum of approximately 96 weeks) | — |
| The time from randomization to the occurrence of individual decompensation events | assessed from randomization up to the end of the study (maximum of approximately 96 weeks | Individual decompensation event is defined as the time from randomization to the first occurrence of each event during the follow-up period. Individual decompensation events include: 1. first variceal bleeding (in patients without prior bleeding history); 2. variceal rebleeding (in patients with prior bleeding history); 3. ascites; 4. HE; 5. jaundice; 6. hepatorenal syndrome (HRS); 7. SBP |
Countries
China
Contacts
CONTACTXingshun Qi, MD
CONTACTLi He
PRINCIPAL_INVESTIGATORLi He
Department of Gastroenterology, General Hospital of Northern Theater Command
Outcome results
None listed