Ignite Creation Date:
2024-05-06 @ 7:27 PM
Last Modification Date:
2024-10-26 @ 3:07 PM
Study NCT ID:
NCT06013670
Status:
RECRUITING
Last Update Posted:
2023-08-28
First Post:
2023-07-14
Brief Title:
Standard Therapy and TIPS for Moderate to High-risk Esophageal and Gastric Variceal Bleeding
Sponsor:
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Organization:
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study Overview
Official Title:
Endoscopic Therapy β Receptor Blockers and TIPS Preventing Rebleeding in Moderate to High-risk Patients With Liver Cirrhosis Esophageal and Gastric Varices A Multicenter Prospective Parallel Open Clinical Study
Status:
RECRUITING
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Comparison of endoscopic therapy combined with non-selective therapy β Receptor blockers NSBBs and TIPS in the treatment of liver cirrhosis
The impact of reducing bleeding on the survival of critically ill patients To compare the effect of endoscopic therapy combined with NSBBs drugs and TIPS on rebleeding and incidence of Hepatic encephalopathy in patients with moderate risk of liver cirrhosis hemorrhage
The impact of reducing bleeding on the survival of critically ill patients To compare the effect of endoscopic therapy combined with NSBBs drugs and TIPS on rebleeding and incidence of Hepatic encephalopathy in patients with moderate risk of liver cirrhosis hemorrhage
Detailed Description:
Portal hypertension PH is one of the most common and serious adverse consequences of liver cirrhosis Its complications including esophageal and gastric variceal bleeding EGVB intractable ascites Hepatorenal syndrome have become the main cause of death in patients with liver cirrhosis In patients with compensated cirrhosis the incidence of varices is 30 -40 while in patients with decompensated cirrhosis the incidence of varices is as high as 85 Varices progress at a rate of 7 -8 annually with an annual bleeding rate of 10 -15 and a 6-week mortality rate of 15 -25 12 Within 1-2 years after the first bleeding approximately 60 of untreated patients experience variceal rebleeding with a mortality rate of about 30 4
In recent years both domestic and international guidelines have recommended the use of endoscopic ligation in the absence of effective risk stratification measures
EVL Joint Non Selective β Receptor blockers NSBBs are the preferred treatment for preventing rebleeding in patients with esophageal and gastric variceal bleeding due to cirrhosis standard treatment while for those who fail standard treatment with rebleeding transjugular intrahepatic portosystemic shunt TIPS is used 4 Although TIPS is significantly superior to standard treatment in the prevention of rebleeding its complications are relatively more especially the portal vein blood flow shunt effectively achieved through TIPS which leads to Hepatic encephalopathy HE caused by insufficient liver perfusion and liver failure More importantly previous studies have not found that TIPS can improve patient survival Two RCTs compared TIPS and EVL for secondary prevention of VB and concluded that TIPS significantly reduced the occurrence of rebleeding without any significant difference in 2-year survival rate 89 This may be due to bias caused by the lack of risk stratification for patients
The level of portal vein pressure is closely related to the prognosis of patients Numerous studies have shown that hepatic vein pressure gradient HVPG can reflect the severity of portal hypertension and it is still the gold standard for diagnosing portal hypertension HVPG has been proven to be the best risk stratification tool for portal hypertension Recently it has also received more and more attention and has been carried out more and more widely 3 Although more and more non-invasive methods can be used in daily clinical practice non-invasive procedures still cannot replace HVPG in decompensated liver cirrhosis patients 3 HVPG 10 mmHg is defined as clinical dominant portal Hypotension CSPH and variceal bleeding is prone to occur when HVPG 12 mmHg In patients with HVPG 16 mmHg the mortality rate of acute variceal bleeding increases HVPG 20 mmHg has become an effective predictor of early rebleeding in clinical practice 12 Recent expert consensus indicates that hierarchical treatment of HVPG is a reasonable clinical strategy
A domestic study in 2015 concluded that risk stratification based on HVPG contributes to the decision of secondary prevention and treatment strategies for esophageal and gastric variceal bleeding in liver cirrhosis 13 However the cut-off point of HVPG in risk stratification has not been clearly demonstrated Based on the value of HVPG target patients can be classified as high-risk HVPG20mmHg medium risk 16mmHg HVPG 20mmHg and low-risk HVPG16mmHg Previous studies have shown that HVPG20mmHg is an independent predictor of rebleeding and frequent death Therefore TIPS has been widely recognized as the preferred method for preventing rebleeding in high-risk patients 16 However there is no consensus on whether to choose TIPS treatment as high-risk patients for moderate to high-risk patients with 16mmHg HVPG 20mmHg In a small study of 49 patients the survival probability of patients with baseline HVPG below 16 mmHg was significantly higher than that of patients with HVPG above 16 mmHg 14 In addition CandidV et al pointed out that HVPG16mmHg is one of the predictive factors for treatment failure in the acute bleeding phase of esophageal and gastric variceal bleeding 15 However there is currently no research indicating that TIPS can improve the prognosis of patients at moderate risk
Our research group has completed three retrospective small sample studies in the early stage For patients with HVPG 20 mmHg TIPS has a significant reduction in rebleeding rate and survival benefits compared to standard treatment propranololEVL consistent with previous studies 17 For medium to high-risk patients TIPS significantly reduced the rate of rebleeding compared to EVLNSBBs during a 2-year follow-up period but did not show significant benefits in improving survival 18 In 2021 our research team conducted a single center retrospective study to compare the clinical efficacy of TIPS and EVLNSBBs based on HVPG related risk stratification for secondary prevention of EGVB in cirrhotic portal hypertension During a 5-year long-term follow-up for patients with HVPG 16mmHg patients receiving TIPS can obtain significant survival benefits and the incidence of dominant Hepatic encephalopathy is not higher than that of the standard treatment group
To further verify the reliability of this conclusion a multicenter prospective parallel open clinical study is planned to explore the treatment strategy of secondary prevention for medium risk patients with 16mmHg HVPG 20mmHg Endoscopic therapy combined with NSBBs drug therapy and TIPS prevention of rebleeding in medium risk patients with esophageal and gastric variceal bleeding due to cirrhosis is of great clinical significance
In recent years both domestic and international guidelines have recommended the use of endoscopic ligation in the absence of effective risk stratification measures
EVL Joint Non Selective β Receptor blockers NSBBs are the preferred treatment for preventing rebleeding in patients with esophageal and gastric variceal bleeding due to cirrhosis standard treatment while for those who fail standard treatment with rebleeding transjugular intrahepatic portosystemic shunt TIPS is used 4 Although TIPS is significantly superior to standard treatment in the prevention of rebleeding its complications are relatively more especially the portal vein blood flow shunt effectively achieved through TIPS which leads to Hepatic encephalopathy HE caused by insufficient liver perfusion and liver failure More importantly previous studies have not found that TIPS can improve patient survival Two RCTs compared TIPS and EVL for secondary prevention of VB and concluded that TIPS significantly reduced the occurrence of rebleeding without any significant difference in 2-year survival rate 89 This may be due to bias caused by the lack of risk stratification for patients
The level of portal vein pressure is closely related to the prognosis of patients Numerous studies have shown that hepatic vein pressure gradient HVPG can reflect the severity of portal hypertension and it is still the gold standard for diagnosing portal hypertension HVPG has been proven to be the best risk stratification tool for portal hypertension Recently it has also received more and more attention and has been carried out more and more widely 3 Although more and more non-invasive methods can be used in daily clinical practice non-invasive procedures still cannot replace HVPG in decompensated liver cirrhosis patients 3 HVPG 10 mmHg is defined as clinical dominant portal Hypotension CSPH and variceal bleeding is prone to occur when HVPG 12 mmHg In patients with HVPG 16 mmHg the mortality rate of acute variceal bleeding increases HVPG 20 mmHg has become an effective predictor of early rebleeding in clinical practice 12 Recent expert consensus indicates that hierarchical treatment of HVPG is a reasonable clinical strategy
A domestic study in 2015 concluded that risk stratification based on HVPG contributes to the decision of secondary prevention and treatment strategies for esophageal and gastric variceal bleeding in liver cirrhosis 13 However the cut-off point of HVPG in risk stratification has not been clearly demonstrated Based on the value of HVPG target patients can be classified as high-risk HVPG20mmHg medium risk 16mmHg HVPG 20mmHg and low-risk HVPG16mmHg Previous studies have shown that HVPG20mmHg is an independent predictor of rebleeding and frequent death Therefore TIPS has been widely recognized as the preferred method for preventing rebleeding in high-risk patients 16 However there is no consensus on whether to choose TIPS treatment as high-risk patients for moderate to high-risk patients with 16mmHg HVPG 20mmHg In a small study of 49 patients the survival probability of patients with baseline HVPG below 16 mmHg was significantly higher than that of patients with HVPG above 16 mmHg 14 In addition CandidV et al pointed out that HVPG16mmHg is one of the predictive factors for treatment failure in the acute bleeding phase of esophageal and gastric variceal bleeding 15 However there is currently no research indicating that TIPS can improve the prognosis of patients at moderate risk
Our research group has completed three retrospective small sample studies in the early stage For patients with HVPG 20 mmHg TIPS has a significant reduction in rebleeding rate and survival benefits compared to standard treatment propranololEVL consistent with previous studies 17 For medium to high-risk patients TIPS significantly reduced the rate of rebleeding compared to EVLNSBBs during a 2-year follow-up period but did not show significant benefits in improving survival 18 In 2021 our research team conducted a single center retrospective study to compare the clinical efficacy of TIPS and EVLNSBBs based on HVPG related risk stratification for secondary prevention of EGVB in cirrhotic portal hypertension During a 5-year long-term follow-up for patients with HVPG 16mmHg patients receiving TIPS can obtain significant survival benefits and the incidence of dominant Hepatic encephalopathy is not higher than that of the standard treatment group
To further verify the reliability of this conclusion a multicenter prospective parallel open clinical study is planned to explore the treatment strategy of secondary prevention for medium risk patients with 16mmHg HVPG 20mmHg Endoscopic therapy combined with NSBBs drug therapy and TIPS prevention of rebleeding in medium risk patients with esophageal and gastric variceal bleeding due to cirrhosis is of great clinical significance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None