Evaluation of Hemodynamic Parameters Following Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Refractory Ascites Clinical Trial

Official title:

Evaluation of Hemodynamic Parameters Following Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04050683
• Other study ID #: PRO 35079
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 25, 2019
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

During a TIPS procedure, a shunt or stent (mesh tube) is passed down the jugular vein (the vein above the collarbone in the neck) using fluoroscopy (real time x-rays) guidance. Then, a stent is inserted between the portal vein (vein that carries blood from the intestines into the liver) to a hepatic vein (vein that carries blood away from the liver back to the heart). This means that blood that would usually gets filtered through the liver is now bypassing the liver and going directly to the heart. Because more blood will be flowing to the heart, the heart needs to be strong enough to handle the extra volume. This study is being done to determine the impact of the TIPS procedure on cardiac (heart) function by collecting data (heart pressures) during the TIPS procedure. Immediately after TIPS and at standard follow-up time points, labs and transthoracic echocardiograms (TTE or echo) will also be collected. The device(s) used in this study are neither the intervention studied nor the experimental variable of interest. Devices are commercially available and used, and procedures are performed, in accordance with the institution's standard of care.

Description:

The long-term goal of this proposal is to improve survival in patients with end stage liver disease following TIPS placement. Given that the most common indications for TIPS placement are also defining features of decompensated cirrhosis, specifically hemorrhage and refractory ascites, the overall health of this patient population is extraordinarily complex. One notable circulatory impact of cirrhosis is the increase in total blood volume in concert with a disproportionate increase in splanchnic blood volume. Therefore, at the time of TIPS placement, a patient may experience a marked increase in central blood volume that may lead to cardiac dysfunction. Considering that a central feature of cirrhotic cardiomyopathy is attenuated response to stress, it is conceivable that some perioperative cardiovascular complications could be attributed to the patient's baseline health rather than an isolated effect of the procedure alone. By instituting measures to identify patients that may be at increased risk for an adverse outcome, this proposal hopes to offer a new paradigm for managing TIPS patients in the acute postoperative setting. Therefore, the purpose of this study is to derive better correlates between non-invasive and invasive measurements of cardiac function.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

OVERALL INCLUSION

• = 18 years
• Patients with indications as established by the ACR-SIR-SPR practice parameters::
• prophylaxis against recurrent variceal bleed in high-risk patients
• portal hypertensive gastropathy or intestine-opathy
• refractory ascites
• hepatic hydrothorax
• hepatopulmonary syndrome
• hepatorenal syndrome
• decompression of portosystemic collaterals prior to abdominal surgical procedures
• Technically successful creation of a TIPS shunt, defined as creation of a portosystemic shunt with post TIPS creation portosystemic gradient of = 12 mmHg

STUDY ARM INCLUSION:

• All patients undergoing elective TIPS who meet at least one of the criteria:
• Right atrial pressure (RAP) = 15mm Hg; OR
• Change in RAP = 10mm Hg; OR
• Peak systolic velocity ratio (PSRV) pressure = 46mm Hg

CONTROL ARM INCLUSION:

• Patients undergoing elective TIPS for control of refractory ascites who do not meet at least one of the criteria outlined above for the study arm. Historical controls: we will use data collected form our own recent institutional review. EXCLUSION All patients who do not exhibit alterations in invasive RAP or PRVS measurements as listed in Inclusion Criteria and do not meet criteria for participation as a control subject (i.e. are not undergoing elective TIPS for control of refractory ascites). Admitted for GI bleed. Budd-Chiari syndrome. TIPS in setting of mesenteric vein thrombosis.

Related Conditions & MeSH terms

• Ascites
• Refractory Ascites

Intervention

Procedure:
• Study - Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Prior to and 1-3 days after the TIPS procedure, the following blood tests are done for research purposes: Brain Natriuretic Peptide (BNP); Endothelin-1; Tumor Necrosis Factor-alpha (TNF-a); Endothelial Nitric Oxide Synthase (eNOS). Subjects with abnormal heart pressures during TIPS will have a right heart catheterization (RHC) to monitor heart function, blood flow, and pressures in and around the heart. The subject will be admitted to the Cardiovascular Intensive Care Unit and have a TTE all of which are standard of care. Routine follow-up visits will occur in IR Clinic at 2 Weeks (± 3 days), 4-6 weeks and 4-6 months. Visits will include: blood draws for research related blood tests as listed above; standard of care ultrasound of the abdomen; TTEs; and for at least one year, routine lab testing, imaging, medications, and subject overall condition will be assessed for long term outcomes. Diagnostic RHC will be done as needed per standard of care.
• Control - Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Subject's with normal heart pressures who are having elective (planned in advance and not due to an emergency) TIPS due to refractory ascites (fluid build up in the belly that does not go away or comes back shortly after being removed). Prior to and 1-3 days after the TIPS procedure, the following blood tests are done for research purposes: Brain Natriuretic Peptide (BNP); Endothelin-1; Tumor Necrosis Factor-alpha (TNF-a); Endothelial Nitric Oxide Synthase (eNOS). The subject will be admitted to the hospital after TIPS for standard of care monitoring. Routine follow-up visits will occur in IR Clinic at 2 Weeks (± 3 days), 4-6 weeks and 4-6 months. Visits will include: blood draws for research related blood tests as listed above; standard of care ultrasound of the abdomen; and for at least one year, routine lab testing, imaging, medications, and subject overall condition will be assessed for long term outcomes.

Locations

Country	Name	City	State
United States	Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Medical College of Wisconsin	Radiological Society of North America

Country where clinical trial is conducted

United States, 

References & Publications (18)

ACR-SIR-SPR Practice Parameter for the Creation of a Transjugular Intrahepatic Portosystemic Shunt (TIPS). :25.

Ascha M, Abuqayyas S, Hanouneh I, Alkukhun L, Sands M, Dweik RA, Tonelli AR. Predictors of mortality after transjugular portosystemic shunt. World J Hepatol. 2016 Apr 18;8(11):520-9. doi: 10.4254/wjh.v8.i11.520. — View Citation

Boyer TD, Haskal ZJ; American Association for the Study of Liver Diseases. The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in the Management of Portal Hypertension: update 2009. Hepatology. 2010 Jan;51(1):306. doi: 10.1002/hep.23383. No abstract available. — View Citation

Colapinto RF, Stronell RD, Birch SJ, Langer B, Blendis LM, Greig PD, Gilas T. Creation of an intrahepatic portosystemic shunt with a Gruntzig balloon catheter. Can Med Assoc J. 1982 Feb 1;126(3):267-8. No abstract available. — View Citation

Ghaferi AA, Birkmeyer JD, Dimick JB. Complications, failure to rescue, and mortality with major inpatient surgery in medicare patients. Ann Surg. 2009 Dec;250(6):1029-34. doi: 10.1097/sla.0b013e3181bef697. — View Citation

Habash F, Gurram P, Almomani A, Duarte A, Hakeem A, Vallurupalli S, Bhatti S. Correlation between Echocardiographic Pulmonary Artery Pressure Estimates and Right Heart Catheterization Measurement in Liver Transplant Candidates. J Cardiovasc Imaging. 2018 Jun;26(2):75-84. doi: 10.4250/jcvi.2018.26.e2. Epub 2018 Jun 22. — View Citation

Hoeper MM, Krowka MJ, Strassburg CP. Portopulmonary hypertension and hepatopulmonary syndrome. Lancet. 2004 May 1;363(9419):1461-8. doi: 10.1016/S0140-6736(04)16107-2. — View Citation

Kiszka-Kanowitz M, Henriksen JH, Moller S, Bendtsen F. Blood volume distribution in patients with cirrhosis: aspects of the dual-head gamma-camera technique. J Hepatol. 2001 Nov;35(5):605-12. doi: 10.1016/s0168-8278(01)00175-1. — View Citation

Liu H, Gaskari SA, Lee SS. Cardiac and vascular changes in cirrhosis: pathogenic mechanisms. World J Gastroenterol. 2006 Feb 14;12(6):837-42. doi: 10.3748/wjg.v12.i6.837. — View Citation

Luo B, Liu L, Tang L, Zhang J, Ling Y, Fallon MB. ET-1 and TNF-alpha in HPS: analysis in prehepatic portal hypertension and biliary and nonbiliary cirrhosis in rats. Am J Physiol Gastrointest Liver Physiol. 2004 Feb;286(2):G294-303. doi: 10.1152/ajpgi.00298.2003. — View Citation

Marcellin P, Kutala BK. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018 Feb;38 Suppl 1:2-6. doi: 10.1111/liv.13682. — View Citation

Nevah MI, Kuruvilla AC, Fallon MB. Cardiopulmonary Complications of Cirrhosis. Zakim and Boyer's Hepatology. 7th ed. Philadelphia, PA: Elsevier; 2018 [cited 2018 Dec 22]. p. 281-292.e5.

Parvinian A, Bui JT, Knuttinen MG, Minocha J, Gaba RC. Right atrial pressure may impact early survival of patients undergoing transjugular intrahepatic portosystemic shunt creation. Ann Hepatol. 2014 Jul-Aug;13(4):411-9. — View Citation

Preston SR, Markar SR, Baker CR, Soon Y, Singh S, Low DE. Impact of a multidisciplinary standardized clinical pathway on perioperative outcomes in patients with oesophageal cancer. Br J Surg. 2013 Jan;100(1):105-12. doi: 10.1002/bjs.8974. Epub 2012 Nov 12. — View Citation

Ruiz-del-Arbol L, Serradilla R. Cirrhotic cardiomyopathy. World J Gastroenterol. 2015 Nov 7;21(41):11502-21. doi: 10.3748/wjg.v21.i41.11502. — View Citation

Sinclair S, James S, Singer M. Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial. BMJ. 1997 Oct 11;315(7113):909-12. doi: 10.1136/bmj.315.7113.909. — View Citation

Tsiakalos A, Hatzis G, Moyssakis I, Karatzaferis A, Ziakas PD, Tzelepis GE. Portopulmonary hypertension and serum endothelin levels in hospitalized patients with cirrhosis. Hepatobiliary Pancreat Dis Int. 2011 Aug;10(4):393-8. doi: 10.1016/s1499-3872(11)60066-0. — View Citation

Xu J, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: Final Data for 2016. Natl Vital Stat Rep. 2018 Jul;67(5):1-76. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of cardiac events with laboratory values	correlations will be made between outcome BNP, TNF-a, eNOS, endothelin-1	labs will be obtained at baseline and post TIPS at 1-3 days, 2 weeks +/- 3 days, 4-6 weeks, and 4-6 months
Primary	Cardiac related events	any cardiac event to include, heart failure, heart attack, pulmonary hypertension	from insertion of TIPS to 2 years post TIPS
Secondary	Clinical success	No further need for paracentesis or thoracentesis at 6 months	6 months after TIPS placement
Secondary	Overall survival	evaluation of overall survival from time of TIPS placement to death	all patients will be followed for 2 years after TIPS placement
Secondary	Complications	Any peri or post procedural TIPS related events including liver failure, need for re-intervention, etc.	from insertion of TIPS to 2 years post TIPS
Secondary	TIPS patency	evaluation of how long the TIPS remains patent without need for further intervention	from insertion of TIPS to 2 years post TIPS