Early TIPS With Polytetrafluoroethylene (PTFE) Covered Stents for High Risk Acute Variceal Bleeding in Cirrhotic Patients - Full Text View

Purpose

The purpose of this study is to determine whether early use of transjugular intrahepatic portosystemic shunt (TIPS) with Polytetrafluoroethylene (PTFE) covered stents is able to prolong the survival in cirrhotic patients with high risk acute variceal bleeding.

Condition	Intervention
Decompensated Cirrhosis Bleeding Varices	Procedure: Transjugular intrahepatic portosystemic shunt Drug: Non-selective beta blocker + Endoscopic treatment

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Early Transjugular Intrahepatic Portosystemic Shunt With Polytetrafluoroethylene Covered Stents Versus Standard Medical Therapy for High Risk Acute Variceal Bleeding in Cirrhotic Patients

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis Endoscopy High Blood Pressure Varicose Veins

U.S. FDA Resources

Further study details as provided by Fourth Military Medical University:

Primary Outcome Measures:

Number of survival without liver transplantation [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of participants failed to control acute variceal bleeding within 5 days, 6 weeks and 1 year [ Time Frame: 1 years ] [ Designated as safety issue: No ]
Number of bleeding related death [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Number of other portal hypertension related complications on follow-up (ascites, hepatorenal syndrome, hepatic encephalopathy) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	July 2011
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TIPS treatment TIPS will be performed as soon as possible once the patients are enrolled in the study, always within the first 72 hours after the diagnostic endoscopy (preferably in the first 24 hours).	Procedure: Transjugular intrahepatic portosystemic shunt A 8 mm Fluency stent will be used, that will be dilated to 8 or 10 mm according to the hemodynamic response. The aim will be to reduce the portal pressure gradient (PPG) below to 25-75% of baseline. Not paralleled TIPS or over-dilatation are allowed. Embolisation, either with coils or bucrylate, can be performed, if it is felt necessary, especially in patients where portography shows the filling of big portosystemic collaterals feeding the varices, in association with a PPG below 16 mmHg After TIPS, anticoagulation will not be used as a rule, but is allowed if the attending physician thinks that it is warranted Other Name: Transjugular intrahepatic portosystemic shunt (TIPS)
Active Comparator: Medical treatment Patients will be treated with non-selective beta-blockers (either propranolol or nadolol). In case of contraindications or intolerance to beta-blockers, patients will not receive pharmacological treatment (beta-blockers but also mononitrate) and the only treatment to prevent rebleeding will be endoscopic band ligation.	Drug: Non-selective beta blocker + Endoscopic treatment Patients will begin treatment with non-selective beta-blockers (either propranolol or nadolol). After an initial dose of 40 mg, the dose of propranolol/nadolol will be increased/decreased step by step to achieve a baseline heart rate of 55 bpm or up to the maximum tolerated dose, within the limit of 160 mg twice a day (bid) for propranolol or to a maximum of 160 mg for nadolol. The first elective session of endoscopic band ligation should be performed within the first 7-14 days. The following sessions will be performed at 14 + 3 days intervals until variceal eradication (defined as disappearance of the varix, impossibility of suctioning the varix, or a maximum of six continued sessions). Once eradication is achieved, a control endoscopy will be performed one month later for confirmation. The following endoscopies will be scheduled at 6 and 12 months of inclusion and yearly thereafter. If varices reappear, new band ligation will follow. Other Name: Non-selective beta blocker + Endoscopic variceal ligation

Arms

Assigned Interventions

Experimental: TIPS treatment

TIPS will be performed as soon as possible once the patients are enrolled in the study, always within the first 72 hours after the diagnostic endoscopy (preferably in the first 24 hours).

Procedure: Transjugular intrahepatic portosystemic shunt

A 8 mm Fluency stent will be used, that will be dilated to 8 or 10 mm according to the hemodynamic response. The aim will be to reduce the portal pressure gradient (PPG) below to 25-75% of baseline. Not paralleled TIPS or over-dilatation are allowed.
Embolisation, either with coils or bucrylate, can be performed, if it is felt necessary, especially in patients where portography shows the filling of big portosystemic collaterals feeding the varices, in association with a PPG below 16 mmHg
After TIPS, anticoagulation will not be used as a rule, but is allowed if the attending physician thinks that it is warranted

Other Name: Transjugular intrahepatic portosystemic shunt (TIPS)

Active Comparator: Medical treatment

Patients will be treated with non-selective beta-blockers (either propranolol or nadolol). In case of contraindications or intolerance to beta-blockers, patients will not receive pharmacological treatment (beta-blockers but also mononitrate) and the only treatment to prevent rebleeding will be endoscopic band ligation.

Drug: Non-selective beta blocker + Endoscopic treatment

Patients will begin treatment with non-selective beta-blockers (either propranolol or nadolol). After an initial dose of 40 mg, the dose of propranolol/nadolol will be increased/decreased step by step to achieve a baseline heart rate of 55 bpm or up to the maximum tolerated dose, within the limit of 160 mg twice a day (bid) for propranolol or to a maximum of 160 mg for nadolol.

The first elective session of endoscopic band ligation should be performed within the first 7-14 days. The following sessions will be performed at 14 + 3 days intervals until variceal eradication (defined as disappearance of the varix, impossibility of suctioning the varix, or a maximum of six continued sessions). Once eradication is achieved, a control endoscopy will be performed one month later for confirmation. The following endoscopies will be scheduled at 6 and 12 months of inclusion and yearly thereafter. If varices reappear, new band ligation will follow.

Other Name: Non-selective beta blocker + Endoscopic variceal ligation

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

History of cirrhosis (clinical or by liver biopsy)
Admission due to acute bleeding from oesophageal or gastric (GOV1 or GOV2) varices
Child-Pugh Class C (Child-Pugh score less than or equal to 13) or Child-Pugh class B
Signed written informed consent

Exclusion Criteria:

Patients not fulfilling inclusion criteria
Pregnancy or breast-feeding
Confirmed hepatocellular carcinoma with any of the following characteristics: one nodule of more than 5 cm; more than 3 greater than 3 cm
Creatinine greater than 3 mg/dl
Terminal hepatic failure (Child-Pugh score greater than 13)
Previous treatment with TIPS or combined pharmacological and endoscopic treatment to prevent rebleeding
Fundal or ectopic gastric variceal bleeding (IGV1 or IGV2)
Portal vein thrombosis or cavernoma
Congestive heart failure New York Heart Association (NYHA) greater than III or medical history of pulmonary hypertension
Spontaneous recurrent hepatic encephalopathy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370161

Contacts

Contact: Zhiping Yang, MD

86-29-84771501

bayern_yang@126.com

Locations

China, Shaanxi
Xijing Hospital of Digestive Diseases, Fourth Military Medical University	Recruiting
Xi'an, Shaanxi, China, 710032
Contact: Zhiping Yang, MD 86-29-84771501 bayern_yang@126.com
Contact: Xingshun Qi, MD 86-29-84771528 qixingshun19840717@126.com
Principal Investigator: Guohong Han, PhD & MD

Sponsors and Collaborators

Fourth Military Medical University

Investigators

Principal Investigator:

Guohong Han, PhD & MD

Xijing Hospital of Digestive Diseases, Fourth Military Medical University

More Information

Publications:

García-Pagán JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A, Abraldes JG, Nevens F, Vinel JP, Mössner J, Bosch J; Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 2010 Jun 24;362(25):2370-9.

Responsible Party:	Guohong Han, Head of Department of Digestive Interventional Radiology, Fourth Military Medical University
ClinicalTrials.gov Identifier:	NCT01370161 History of Changes
Other Study ID Numbers:	XHDD 002, FMMU-XHDD 002
Study First Received:	June 7, 2011
Last Updated:	February 17, 2013
Health Authority:	China: Ethics Committee

Keywords provided by Fourth Military Medical University:

transjugular intrahepatic portosystemic shunt
TIPS
variceal bleeding
liver cirrhosis
hepatitis B

Additional relevant MeSH terms:

Hemorrhage
Liver Cirrhosis
Fibrosis
Varicose Veins
Pathologic Processes
Liver Diseases
Digestive System Diseases
Vascular Diseases

Cardiovascular Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 19, 2013