Ignite Creation Date:
2024-05-05 @ 5:12 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00401895
Status:
TERMINATED
Last Update Posted:
2009-01-09
First Post:
2006-11-17
Brief Title:
Transjugular Intrahepatic Portosystemic Shunt With 8- or 10-mm Covered Stents
Sponsor:
University of Roma La Sapienza
Organization:
University of Roma La Sapienza
Study Overview
Official Title:
Clinical Efficacy of Transjugular Intrahepatic Portosystemic Shunt With 8- or 10-mm Covered Stents in Cirrhotic Patients A Randomized Controlled Study
Status:
TERMINATED
Status Verified Date:
2009-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
An interim analysis revealed a significantly higher persistencerecurrence of complications of portal hypertension in the 8 mm-stent group
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Coated stents with different diameters are presently commercially available but clinical studies on the assessment of the best stent diameter for a better clinical efficacy a reduced number of complications and an effective portal pressure reduction essential in the treatment of those pathologies in which TIPS is indicated still do not exist
Aim of the study The purpose of our study is to compare the clinical efficacy and the incidence of complications of TIPS created with 8- and 10-mm covered stents in patients with hepatic cirrhosis
Aim of the study The purpose of our study is to compare the clinical efficacy and the incidence of complications of TIPS created with 8- and 10-mm covered stents in patients with hepatic cirrhosis
Detailed Description:
Clinical Efficacy of Transjugular Intrahepatic Portosystemic Shunt With 8- or 10-mm Covered Stents in Cirrhotic Patients
A Randomized Controlled Study
Introduction In the treatment of esophageal varices rebleeding1 and asciteshydrothorax refractory to the diuretic therapy2 by transjugular intrahepatic portosystemic shunt TIPS shunt stenosis occurring in 30-70 of cases during the first post-procedural year and the onset of hepatic encephalopathy 30-55 of cases at one year represent two major problems
Since the year 2000 a new polytetrafluoroethylene covered stent has highly improved TIPS patency thus inducing a remarkable reduction of rebleeding incidence Some authors however suggest that the maintenance of the shunt patency may involve an increased risk of hepatic encephalopathy although the data in the present literature are limited and controversial The only randomized controlled study3 available in fact reports a lower incidence of hepatic encephalopathy in those patients treated with covered stents as compared with those treated with conventional metallic stents In our preliminary experience4 instead a similar incidence of hepatic encephalopathy was noted in both groups In addition in the group of patients treated by covered stents a higher number of cases with persistent and intractable hepatic encephalopathy requiring shunt reduction was recorded5 Post-TIPS hepatic encephalopathy incidence increases with the decrease of post-procedure portal pressure which depends on the caliber of the stent used to create the anastomosis This might suggest the use of covered stents with a smaller diameter aimed at reducing the risk of hepatic encephalopathy Coated stents with different diameters are presently commercially available but clinical studies on the assessment of the best stent diameter for a better clinical efficacy a reduced number of complications and an effective portal pressure reduction essential in the treatment of those pathologies in which TIPS is indicated still do not exist
Aim of the study The purpose of our study is to compare the clinical efficacy and the incidence of complications of TIPS created with 8- and 10-mm covered stents in patients with hepatic cirrhosis
Methods All consecutive cirrhotic patients who have undergone TIPS at our Department for bleeding of esophagogastric varices refractory to medical or endoscopic treatment or for asciteshydrothorax refractory to diuretic therapy will be considered eligible for the study
Before the TIPS procedure all the patients will undergo a complete clinical evaluation including psychometric tests to assess their past or present history of hepatic encephalopathy their Child-Pugh and MELD scores will be determined abdominal ultrasounds and esophagogastroduodenoscopies will be also carried out The patients will be then randomized into two groups to undergo TIPS with either 8- or 10-mm covered stents VIATORR W L Gore Associates Inc Flagstaff AZ The two groups will be followed up according to the same post-TIPS protocol
an outpatient consultation one month post-procedure and every three months thereafter or when clinically necessary Each consultation will include a clinical exam Child-Pugh and MELD scores determination and hepatic encephalopathy assessment
a post-procedure ultrasound will be carried out at one and four weeks at three and six months and every six months thereafter or in case of bleeding recurrence or ascites
a follow-up esophagogastroduodenoscopy will be performed at one week and at one month following TIPS and every six months thereafter or when necessary
an angiography will be done in presence of shunt dysfunction bleeding or ascites recurrence due portal hypertension or in case of variceal recurrence at risk of bleeding associated with signs of shunt dysfunction at ultrasound
The following study end-points are defined
hepatic encephalopathy incidence the hepatic encephalopathy grade will be evaluated according to the modified West Haven Criteria Those patients presenting grade II lethargy apathy personality changes inappropriate behavior minimal disorientation for time or place or higher grades of hepatic encephalopathy episodes will reach the main study end-point
incidence of persistent hepatic encephalopathy defined as the presence of a continuous mental state alteration with episodes of further worsening episodes
incidence of recurrent hepatic encephalopathy defined as the onset of at least three episodes of open hepatic encephalopathy in a six-month period
incidence of variceal rebleeding defined as the finding at esophagogastroduodenoscopy of ongoing or recent variceal hemorrhage or the finding of blood in the stomach and the presence of varices as the only potential cause of bleeding
shunt dysfunction defined as the finding of a portosystemic gradient higher than 12 mm Hg and angiographic evidence of shunt stenosis or occlusion
recurrence of ascites defined as the need of performing at least one evacuation of ascitic fluid with paracentesis
survival all deaths of any cause will be recorded All mortalities occurring within a six-week period from a digestive bleeding episode will be considered as related to the bleeding itself All deaths occurring within 30 days post-TIPS placement will be considered as early mortality
Sample size The sample size will be calculated on the main study end-point the incidence of hepatic encephalopathy On the basis of previous studies the post-TIPS incidence of hepatic encephalopathy is considered to be of 50 at one year To obtain a clinically significant from 50 to 25 encephalopathy incidence reduction a 5 and b 20 it will be therefore necessary to enroll 57 patients per group Randomization will be by sealed envelopes in blocks of ten
Statistical analysis The comparability of the two groups treated with 8- or 10-mm covered stents will be verified by c2 o Student t-test The incidence of hepatic encephalopathy main study end-point shunt dysfunction rebleeding recurrence of ascites and mortality secondary end-points will be calculated by Kaplan-Meier method and compared by Log-rank test The Number Cruncher Statistical System NCSS software will be employed
The rules and guidelines of the Good Clinical Practice and all legal requirements on sensitive data storage and experimental protocols will be followed
References
1 Merli M Salerno F Riggio O et al Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotheraphy for the prevention of variceal bleeding in cirrhosis a randomized multicenter trial Hepatology 1998 27 40-45
2 Salerno F Merli M Riggio O Cazzaniga M Valeriano V Pozzi M Nicolini A Salvatori F and GIST Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites Hepatology 2004 40 629-635
3 Bureau C Garcia-Pagan JC Otal P Pomier-Layrgrargues G et al Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS results of a randomized study Gastroenterology 2004 126 469-475
4 Angeloni S Merli M Salvatori F De Santis A Fanelli F Pepino D Attili AF Rossi P Riggio O Polytetrafluorethylene-covered stent-graft for TIPS procedure 1-year patency and clinical results Am J Gastroenterol 2004 99280-285
5 Riggio O Nicolao F Angeloni S Masini A Salvatori F Fanelli F Efrati C Merli M Intractable hepatic encephalopathy after TIPS with polytetrafluoroethylene-covered stent-graft
Scand J Gastroenterol 200338570-2
A Randomized Controlled Study
Introduction In the treatment of esophageal varices rebleeding1 and asciteshydrothorax refractory to the diuretic therapy2 by transjugular intrahepatic portosystemic shunt TIPS shunt stenosis occurring in 30-70 of cases during the first post-procedural year and the onset of hepatic encephalopathy 30-55 of cases at one year represent two major problems
Since the year 2000 a new polytetrafluoroethylene covered stent has highly improved TIPS patency thus inducing a remarkable reduction of rebleeding incidence Some authors however suggest that the maintenance of the shunt patency may involve an increased risk of hepatic encephalopathy although the data in the present literature are limited and controversial The only randomized controlled study3 available in fact reports a lower incidence of hepatic encephalopathy in those patients treated with covered stents as compared with those treated with conventional metallic stents In our preliminary experience4 instead a similar incidence of hepatic encephalopathy was noted in both groups In addition in the group of patients treated by covered stents a higher number of cases with persistent and intractable hepatic encephalopathy requiring shunt reduction was recorded5 Post-TIPS hepatic encephalopathy incidence increases with the decrease of post-procedure portal pressure which depends on the caliber of the stent used to create the anastomosis This might suggest the use of covered stents with a smaller diameter aimed at reducing the risk of hepatic encephalopathy Coated stents with different diameters are presently commercially available but clinical studies on the assessment of the best stent diameter for a better clinical efficacy a reduced number of complications and an effective portal pressure reduction essential in the treatment of those pathologies in which TIPS is indicated still do not exist
Aim of the study The purpose of our study is to compare the clinical efficacy and the incidence of complications of TIPS created with 8- and 10-mm covered stents in patients with hepatic cirrhosis
Methods All consecutive cirrhotic patients who have undergone TIPS at our Department for bleeding of esophagogastric varices refractory to medical or endoscopic treatment or for asciteshydrothorax refractory to diuretic therapy will be considered eligible for the study
Before the TIPS procedure all the patients will undergo a complete clinical evaluation including psychometric tests to assess their past or present history of hepatic encephalopathy their Child-Pugh and MELD scores will be determined abdominal ultrasounds and esophagogastroduodenoscopies will be also carried out The patients will be then randomized into two groups to undergo TIPS with either 8- or 10-mm covered stents VIATORR W L Gore Associates Inc Flagstaff AZ The two groups will be followed up according to the same post-TIPS protocol
an outpatient consultation one month post-procedure and every three months thereafter or when clinically necessary Each consultation will include a clinical exam Child-Pugh and MELD scores determination and hepatic encephalopathy assessment
a post-procedure ultrasound will be carried out at one and four weeks at three and six months and every six months thereafter or in case of bleeding recurrence or ascites
a follow-up esophagogastroduodenoscopy will be performed at one week and at one month following TIPS and every six months thereafter or when necessary
an angiography will be done in presence of shunt dysfunction bleeding or ascites recurrence due portal hypertension or in case of variceal recurrence at risk of bleeding associated with signs of shunt dysfunction at ultrasound
The following study end-points are defined
hepatic encephalopathy incidence the hepatic encephalopathy grade will be evaluated according to the modified West Haven Criteria Those patients presenting grade II lethargy apathy personality changes inappropriate behavior minimal disorientation for time or place or higher grades of hepatic encephalopathy episodes will reach the main study end-point
incidence of persistent hepatic encephalopathy defined as the presence of a continuous mental state alteration with episodes of further worsening episodes
incidence of recurrent hepatic encephalopathy defined as the onset of at least three episodes of open hepatic encephalopathy in a six-month period
incidence of variceal rebleeding defined as the finding at esophagogastroduodenoscopy of ongoing or recent variceal hemorrhage or the finding of blood in the stomach and the presence of varices as the only potential cause of bleeding
shunt dysfunction defined as the finding of a portosystemic gradient higher than 12 mm Hg and angiographic evidence of shunt stenosis or occlusion
recurrence of ascites defined as the need of performing at least one evacuation of ascitic fluid with paracentesis
survival all deaths of any cause will be recorded All mortalities occurring within a six-week period from a digestive bleeding episode will be considered as related to the bleeding itself All deaths occurring within 30 days post-TIPS placement will be considered as early mortality
Sample size The sample size will be calculated on the main study end-point the incidence of hepatic encephalopathy On the basis of previous studies the post-TIPS incidence of hepatic encephalopathy is considered to be of 50 at one year To obtain a clinically significant from 50 to 25 encephalopathy incidence reduction a 5 and b 20 it will be therefore necessary to enroll 57 patients per group Randomization will be by sealed envelopes in blocks of ten
Statistical analysis The comparability of the two groups treated with 8- or 10-mm covered stents will be verified by c2 o Student t-test The incidence of hepatic encephalopathy main study end-point shunt dysfunction rebleeding recurrence of ascites and mortality secondary end-points will be calculated by Kaplan-Meier method and compared by Log-rank test The Number Cruncher Statistical System NCSS software will be employed
The rules and guidelines of the Good Clinical Practice and all legal requirements on sensitive data storage and experimental protocols will be followed
References
1 Merli M Salerno F Riggio O et al Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotheraphy for the prevention of variceal bleeding in cirrhosis a randomized multicenter trial Hepatology 1998 27 40-45
2 Salerno F Merli M Riggio O Cazzaniga M Valeriano V Pozzi M Nicolini A Salvatori F and GIST Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites Hepatology 2004 40 629-635
3 Bureau C Garcia-Pagan JC Otal P Pomier-Layrgrargues G et al Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS results of a randomized study Gastroenterology 2004 126 469-475
4 Angeloni S Merli M Salvatori F De Santis A Fanelli F Pepino D Attili AF Rossi P Riggio O Polytetrafluorethylene-covered stent-graft for TIPS procedure 1-year patency and clinical results Am J Gastroenterol 2004 99280-285
5 Riggio O Nicolao F Angeloni S Masini A Salvatori F Fanelli F Efrati C Merli M Intractable hepatic encephalopathy after TIPS with polytetrafluoroethylene-covered stent-graft
Scand J Gastroenterol 200338570-2
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