Ignite Creation Date:
2024-10-25 @ 8:01 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06549673
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-08
Brief Title:
Safety of Discontinuing NSBBs in Cirrhotic Patients With Managed Primary Aetiological Factors
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Assessing the Safety of Discontinuing Non-selective Beta-blockers in Cirrhotic Patients With Managed Primary Aetiological Factors According to Baveno VII Consensus
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This multicentre prospective cohort study aims to enrol 375 patients with cirrhosis who meet the following criteria
1 effective management or elimination of the primary aetiological factor ie sustained virological response in chronic hepatitis C complete viral suppression in chronic hepatitis B or long-term alcohol abstinence in alcohol-related liver disease
2 liver stiffness measurements under 25 kPa and
3 absence of varices as confirmed by endoscopy
Following the cessation of non-selective beta-blockers patients will undergo a follow-up endoscopy at the one-year mark The studys primary endpoint is recurrent varices in 1 year Success will be defined as the upper bound of the 95 confidence interval for recurrent varices being 5 Should this criterion be met the study will extend to predefined analyses of variceal haemorrhage and hepatic decompensation at 3-and 10-year intervals funded through local resources the General Research Fund will cover patient recruitment costs for 1 year Clinical assessments laboratory tests liver and spleen stiffness measurements will be performed at baseline 3 months 6 months and 12 months to identify potential predictors of variceal recurrence and assess the feasibility of early identification
1 effective management or elimination of the primary aetiological factor ie sustained virological response in chronic hepatitis C complete viral suppression in chronic hepatitis B or long-term alcohol abstinence in alcohol-related liver disease
2 liver stiffness measurements under 25 kPa and
3 absence of varices as confirmed by endoscopy
Following the cessation of non-selective beta-blockers patients will undergo a follow-up endoscopy at the one-year mark The studys primary endpoint is recurrent varices in 1 year Success will be defined as the upper bound of the 95 confidence interval for recurrent varices being 5 Should this criterion be met the study will extend to predefined analyses of variceal haemorrhage and hepatic decompensation at 3-and 10-year intervals funded through local resources the General Research Fund will cover patient recruitment costs for 1 year Clinical assessments laboratory tests liver and spleen stiffness measurements will be performed at baseline 3 months 6 months and 12 months to identify potential predictors of variceal recurrence and assess the feasibility of early identification
Detailed Description:
11 Significance of cirrhosis and portal hypertension
Liver cirrhosis is the common final pathway of various chronic liver diseases Globally mortality due to cirrhosis have risen from 899 000 in 1990 to 132 million deaths in 2017 Additionally as of 2017 112 million and 106 million people were living with compensated and decompensated cirrhosis respectively Portal hypertension stands out as the primary cause of cirrhotic complications such as ascites and variceal haemorrhage Accurate diagnosis of clinically significant portal hypertension is crucial because the administration of non-selective beta-blockers NSBBs can reduce the risk of variceal haemorrhage and hepatic decompensation
Chronic liver disease is highly prevalent in Hong Kong A community screening study in Hong Kong in 2015-2016 indicated that the prevalence of hepatitis B surface antigen was still 78 Studies by our group have further highlighted the extent of the problem revealing that 26 of the local population and a staggering 73 of patients with type 2 diabetes suffer from metabolic dysfunction-associated steatotic liver disease These chronic liver diseases carry a significant risk of progressing to cirrhosis and hepatic decompensation
12 Non-invasive assessment of portal hypertension
Historically the gold standard for assessing portal hypertension requires the measurement of hepatic venous pressure gradient an invasive procedure rarely performed outside research settings However accumulating data support the use of non-invasive tests to assess portal hypertension Specifically liver stiffness measurement LSM through vibration-controlled transient elastography reflects the degree of liver fibrosis and the severity of cirrhosis Furthermore the platelet count reflects whether a patient with cirrhosis has hypersplenism secondary to portal hypertension Additionally spleen stiffness measurement SSM may be an even more direct evaluation of portal hypertension and has been used to ascertain improvements in portal hypertension following the initiation of NSBB Based on existing data the latest Baveno VII consensus has endorsed the use of these non-invasive tests to rule out if LSM 15 kPa and platelet count 15010e9L and to confirm if LSM 25 kPa the presence of clinically significant portal hypertension
In a randomised controlled trial involving 548 patients with radiological cirrhosis our group demonstrated that LSMSSM was non-inferior to routine endoscopy in detecting varices and preventing future variceal haemorrhage Furthermore we validated the use of LSM-based criteria for excluding the presence of varices requiring treatment across a range of chronic liver diseases including patients with or without hepatocellular carcinoma Additionally we reported the natural history of patients falling within the grey zone according to the Baveno VII criteria Importantly we identified factors associated with hepatic decompensation in this specific patient population
13 Emerging concept hepatic recompensation and reversal of cirrhosis and portal hypertension
As a number of chronic liver diseases can now be well controlled or cured it is increasingly apparent that cirrhosis can resolve over time when the primary aetiology is controlled Reports have also emerged suggesting an improvement in portal hypertension and even hepatic recompensation in such circumstances This has led to the practical recommendation on discontinuing NSBB in patients with LSM 25 kPa after removal or suppression of the primary aetiological factor in the absence of varices Removal or suppression of the primary aetiological factor includes sustained virological response in chronic hepatitis C complete hepatitis B virus DNA suppression in chronic hepatitis B patients and long-term abstinence from alcohol in those with alcohol-related liver disease Nonetheless it is crucial to note that these recommendations are based on tenuous evidence C2 recommendation While cessation of NSBB in patients no longer requiring it can reduce unnecessary expenses prescription and monitoring and side effects it remains imperative to confirm the safety of this approach through well-designed prospective studies
Liver cirrhosis is the common final pathway of various chronic liver diseases Globally mortality due to cirrhosis have risen from 899 000 in 1990 to 132 million deaths in 2017 Additionally as of 2017 112 million and 106 million people were living with compensated and decompensated cirrhosis respectively Portal hypertension stands out as the primary cause of cirrhotic complications such as ascites and variceal haemorrhage Accurate diagnosis of clinically significant portal hypertension is crucial because the administration of non-selective beta-blockers NSBBs can reduce the risk of variceal haemorrhage and hepatic decompensation
Chronic liver disease is highly prevalent in Hong Kong A community screening study in Hong Kong in 2015-2016 indicated that the prevalence of hepatitis B surface antigen was still 78 Studies by our group have further highlighted the extent of the problem revealing that 26 of the local population and a staggering 73 of patients with type 2 diabetes suffer from metabolic dysfunction-associated steatotic liver disease These chronic liver diseases carry a significant risk of progressing to cirrhosis and hepatic decompensation
12 Non-invasive assessment of portal hypertension
Historically the gold standard for assessing portal hypertension requires the measurement of hepatic venous pressure gradient an invasive procedure rarely performed outside research settings However accumulating data support the use of non-invasive tests to assess portal hypertension Specifically liver stiffness measurement LSM through vibration-controlled transient elastography reflects the degree of liver fibrosis and the severity of cirrhosis Furthermore the platelet count reflects whether a patient with cirrhosis has hypersplenism secondary to portal hypertension Additionally spleen stiffness measurement SSM may be an even more direct evaluation of portal hypertension and has been used to ascertain improvements in portal hypertension following the initiation of NSBB Based on existing data the latest Baveno VII consensus has endorsed the use of these non-invasive tests to rule out if LSM 15 kPa and platelet count 15010e9L and to confirm if LSM 25 kPa the presence of clinically significant portal hypertension
In a randomised controlled trial involving 548 patients with radiological cirrhosis our group demonstrated that LSMSSM was non-inferior to routine endoscopy in detecting varices and preventing future variceal haemorrhage Furthermore we validated the use of LSM-based criteria for excluding the presence of varices requiring treatment across a range of chronic liver diseases including patients with or without hepatocellular carcinoma Additionally we reported the natural history of patients falling within the grey zone according to the Baveno VII criteria Importantly we identified factors associated with hepatic decompensation in this specific patient population
13 Emerging concept hepatic recompensation and reversal of cirrhosis and portal hypertension
As a number of chronic liver diseases can now be well controlled or cured it is increasingly apparent that cirrhosis can resolve over time when the primary aetiology is controlled Reports have also emerged suggesting an improvement in portal hypertension and even hepatic recompensation in such circumstances This has led to the practical recommendation on discontinuing NSBB in patients with LSM 25 kPa after removal or suppression of the primary aetiological factor in the absence of varices Removal or suppression of the primary aetiological factor includes sustained virological response in chronic hepatitis C complete hepatitis B virus DNA suppression in chronic hepatitis B patients and long-term abstinence from alcohol in those with alcohol-related liver disease Nonetheless it is crucial to note that these recommendations are based on tenuous evidence C2 recommendation While cessation of NSBB in patients no longer requiring it can reduce unnecessary expenses prescription and monitoring and side effects it remains imperative to confirm the safety of this approach through well-designed prospective studies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None