TIPS in Fundal Variceal Bleeding (the TFB Study) (TFB)
Efficacy of Early-TIPS in the Treatment of Acute Variceal Bleeding From Gastric Fundal Varices: a RCT vs Standard Therapy
In the last years, important advances have been done in the treatment and prevention of fundal variceal bleeding in patients with cirrhosis. Experts agree that the combination of pharmacological and endoscopic therapy (with tissue adhesives) should be the first line therapy in the acute bleeding episode from isolated gastric varices (IGV1) or type 2 gastroesophageal varices (GOV2) varices; whereas transjugular intrahepatic portosystemic shunt (TIPS) is considered a rescue therapy. TIPS has been shown to effectively prevent variceal rebleeding but with a potential increase in the incidence of hepatic encephalopathy and/or liver failure. In this sense, a recent randomized controlled trial (RCT) in esophageal variceal bleeding showed that an early TIPS, performed during the first 72h after patient admission resulted in a significant decrease in failure to control bleeding and early and late rebleeding. Moreover, survival was also significantly increased as well as other portal-hypertension related complications (ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, etc).
The present study is directed at comparing the outcome of patients with acute bleeding from fundal varices (IGV1 or GOV2) treated by standard therapy (vasoactive drugs + endoscopic injection of tissue adhesives) with or without early TIPS (performed during the first 1-5 days after admission). Main end-point will be survival free of variceal rebleeding at 1 year from inclusion.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Lleida, Spain
- Recruiting
- Hospital Arnau de Vilanova
-
Contact:
- Carles Aracil, MD
- Email: carbla34@gmail.com
-
-
Catalonia
-
Badalona, Catalonia, Spain
- Recruiting
- Hospital Germans Trias i Pujol
-
Contact:
- Rosa Morillas, MD
-
Barcelona, Catalonia, Spain
- Recruiting
- Hospital del Mar
-
Contact:
- José Carrión, MD
-
Barcelona, Catalonia, Spain, 08036
- Recruiting
- ICU Liver Unit. Hospital Clinic of Barcelona
-
Contact:
- Angels Escorsell, MD
- Phone Number: 4030 34932275400
- Email: aescor@clinic.cat
-
Principal Investigator:
- Angels Escorsell, MD
-
Barcelona, Catalonia, Spain
- Recruiting
- Hospital de La Santa Creu I Sant Pau
-
Contact:
- Càndid Villanueva, MD
- Email: cvillanueva@santpau.cat
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients developing acute variceal bleeding from GOV2 and/or IGV1 defined according to Baveno II criteria, admitted in the Hospital and receiving standard combined medical therapy (somatostatin 3 mg/12h continuous IV infusion or terlipressin, 2mg/4h IV + endoscopic injection of tissue adhesives as per center protocol).
Exclusion Criteria:
- Hepatocarcinoma without therapeutic options (according to Milan criteria).
- Portal or mesenteric vein thrombosis avoiding the performance of TIPS.
- Acute alcoholic hepatitis.
- Platelet count < 20.000/mm3.
- Previous treatment with portosystemic shunt.
- Pregnancy.
- Previous inclusion in the current study.
- Terminal liver disease (bilirrubin > 10 mg/dL and/or prothrombin index < 30%); or other fatal non-liver diseases.
- Denied informed consent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Early TIPS
Standard treatment to achieve initial hemostasis: vasoactive drugs (somatostatin or terlipressin) + endoscopic injection of tissue adhesives according to the center protocol. Performance of TIPS in the first 5 days following acute gastric variceal bleeding. |
TIPS (first 5 days)
|
|
Placebo Comparator: Control
Standard treatment to achieve initial hemostasis: vasoactive drugs (somatostatin or terlipressin) + endoscopic injection of tissue adhesives according to the center protocol. Standard combined endoscopic and pharmacological therapy as a secondary prophylaxis (beta-blockers or carvedilol + repeated injection of tissue adhesives until the erradication of the fundal varices). |
TIPS (first 5 days)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Combined: Absence of rebleeding + survival
Time Frame: 1 year
|
The primary endpoint combines absence of rebleeding + survival during the first 1 year after inclusion in the study.
Patients to compare are those with liver cirrhosis and acute bleeding from IGV1 or GOV2 varices initially treated with combined pharmacological and endoscopic therapy.
Those patients will be randomized to receive a TIPS or standard medical therapy (pharmacological + endoscopic injection of tissue adhesives)
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Absence of portal hypertension-related complications (ascites, spontaneous bacterial peritonitis, hepatorenal syndrome)
Time Frame: 6 weeks and 1 year
|
Comparison of the development of portal-hypertension related complications.
|
6 weeks and 1 year
|
|
Transfusional requirements
Time Frame: 6 weeks and 1 year
|
We will compare the number of packed red blood cells required by each treatment arms as a surrogate of rebleeding.
|
6 weeks and 1 year
|
|
Individual adverse events
Time Frame: 1 year
|
Related and not related to the therapies under study.
|
1 year
|
|
Hospital stay
Time Frame: 1 year
|
Including the stay for the index bleed and also readmissions due to complications of liver disease.
|
1 year
|
|
Use of hospital resources
Time Frame: 1 year
|
Use of hospital resources other than specified in the treatment arms (TIPS, revision of TIPS patency, derivative surgery or additional endoscopic therapy).
|
1 year
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Angels Escorsell, MD, Senior Consultant. Liver Unit
Publications and helpful links
General Publications
- Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007 Sep;46(3):922-38. doi: 10.1002/hep.21907. No abstract available. Erratum In: Hepatology. 2007 Dec;46(6):2052.
- Garcia-Tsao G, Bosch J, Groszmann RJ. Portal hypertension and variceal bleeding--unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single-topic conference. Hepatology. 2008 May;47(5):1764-72. doi: 10.1002/hep.22273. No abstract available.
- Garcia-Pagan JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A, Abraldes JG, Nevens F, Vinel JP, Mossner 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. doi: 10.1056/NEJMoa0910102.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ET_GV15
- PI 14/00392 (Other Grant/Funding Number: Instituto de Salud Carlos III)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.