Periinterventional Coagulation Management of Patients Undergoing a TIPS (TIPSprosp)

Optimizing Periinterventional Coagulation Management of Patients Undergoing a Transjugular Intrahepatic Portosystemic Shunt Implantation: A Prospective Randomized Cohort Study

Assess whether a pre-interventional thrombelastography guided algorithm for assessing and correction of coagulation status in cirrhotic patients is safe and effective

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Procedure: thrombelastogram; Procedure: standard of care

Detailed Description

Transjugular intrahepatic portosystemic shunt (TIPS) is a very effective procedure to treat complications of portal hypertension in liver cirrhosis. TIPS implantation is indicated in cirrhotic patients to treat or prevent portal hypertensive bleeding and to treat refractory ascites.

During this procedure an artificial connection between portal vein and hepatic vein is placed via an image-guided endovascular approach. Although the procedure is very effective and reasonably safe, several complications can occur.

Due to the underlying cirrhosis, morbidity and mortality of TIPS is high, with a 30-day mortality between 7 and 20%. Procedural site complications (transhepatic and transvenous access), bleeding, development of hepatic encephalopathy or other organ complications and stent complications comprise a considerable risk to the patients, however, the improvement of mortality, renal function and liver function outweighs the risks of the procedure. Optimal patient selection and preoperative preparation is crucial to avoid complications of this procedure.

In liver cirrhosis, coagulation disturbances are common. In hepatic insufficiency, a balanced reduction in the levels of most of pro- and anticoagulant proteins produced in the liver does not impair thrombin generation until levels are quite low. However, the ability of the coagulation system to tolerate or recover from an insult is markedly impaired in liver disease. This allows the coagulation system to be more easily tipped into a state favouring either haemorrhage or thrombosis. The American Gastroenterology Association has recently published best practice advices to manage coagulation in cirrhosis. This review concludes that commonly used global coagulation tests are not optimal to assess the risk of bleeding in cirrhosis. A randomized controlled trial showed, that the use of thrombelastography (TEG) to assess coagulation in cirrhosis resulted in a significantly lower usage of blood products with no increase in bleeding rates.

The bleeding risk for TIPS implantation is not well studied, ranging from 0.6-4.3% of fatal bleeding complications in older uncontrolled case series. No evidenced-based recommendations exist for the correction of coagulation abnormalities before TIPS - and the few existing recommendations are not backed with evidence but rather "eminence based". Currently, global tests of coagulation (prothrombin time and platelet count) are used to guide coagulation correction. Mostly, cut-offs without sufficient evidence (PT >50%/ INR >1.8 and platelets >50 G/L) are used for correction of coagulation.

Also, the risk of stent thrombosis needs to be considered, therefore "blind" substitution of clotting factors or platelet transfusions is not advisable. Unfortunately, the study by De Pietri et al. (6) did only include one patient undergoing TIPS (in the standard of care (SOC) arm), therefore it is yet unknown, whether TEG is useful for guiding the correction of coagulation abnormalities in cirrhosis.

The aim of this trial is to assess, whether TEG guided pre-interventional assessment and correction of coagulation in cirrhotic patients is safe and effective

The study will be performed as a single-center, open-label, randomized prospective cohort study

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Recruiting
    • Department of Internal Medicine, Medical University of Graz
    • Contact: Vanessa Stadlbauer, MD; Phone Number: 82282 0043316385; Email: vanessa.stadlbauer@medunigraz.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

inclusion criteria

• Liver cirrhosis
• >18 years
• Indication for TIPS implantation
• Ability to sign informed consent exclusion criteria
• Contraindications against TIPS implantation
• Hepatocellular carcinoma BCLC D
• Ongoing bleeding
• pre-existing anticoagulant therapy at time of inclusion
• administration of blood products within 1 week prior to the enrolment
• Other malignancies that lead to an impaired 90-day survival
• Inherit blood clotting disorders
• Hepatic encephalopathy grade 3 or 4
• any other condition or circumstance, which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thrombelastogram (TEG); Patients in the TEG group will receive prothrombin complex concentrates (PCC) at a dose of 10 IE/kg of ideal body weight, when R-time was greater than 40 minutes (2400 sec) and they will receive platelet transfusion in the amount of 1 apheresis unit when MA was below 30 mm.	Procedure: thrombelastogram; Patients in the TEG group will receive prothrombin complex concentrates (PCC) at a dose of 10 IE/kg of ideal body weight, when R-time was greater than 40 minutes (2400 sec) and they will receive platelet transfusion in the amount of 1 apheresis unit when MA was below 30 mm
Experimental: Standard of Care (SOC); In the SOC group, patients will receive PCC at the dose of 10 IE /kg of ideal body weight when the PT is below 50% and/or INR>1.8 and/or received platelet transfusion in the amount of 1 apheresis when platelet count is below 50 G/L	Procedure: standard of care; 2) In the SOC group, patients will receive PCC at the dose of 10 IE /kg of ideal body weight when the PT is below 50% and/or INR>1.8 and/or received platelet transfusion in the amount of 1 apheresis when platelet count is below 50 G/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood product requirement	Amount of blood products (coagulation factors and platelet transfusions) transfused for pre-interventional correction of coagulation status	2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality rate	90 days
Bleeding	Rate of bleeding complications (BARC criteria)	90 days
complications	Rate of transfusion related complications	90 days
Modified TIPS Score (MOTS)	Predictive power of modified TIPS score (MOTS) using the routine parameter, bilirubin, urea and INR; values range from 0-3, high score means worse outcome	90 days
Factor XIII	Comparison of measured FXIII activity levels with TEG parameters (alpha-angle, K-time, MA) for assessing feasibility of TEG in predicting deficiency of FXIII activity in these specific group of patients.	2 days

Collaborators and Investigators

• Sponsor: Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: TIPS-prospective

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No