TIPS Procedure for Liver Cirrhosis and Muscle Loss

Overseen By Khashayar Farsad, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Oregon Health and Science University

Disqualifiers: Cancer, Hepatic encephalopathy, Sepsis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a procedure called TIPS (Transjugular Intrahepatic Portosystemic Shunt) might benefit individuals with liver cirrhosis awaiting a liver transplant. Researchers aim to determine if TIPS can increase muscle mass and enhance physical function, potentially leading to better overall health outcomes. Participants will either undergo the TIPS procedure or continue with their usual treatment for comparison. The trial seeks individuals with cirrhosis experiencing issues like fluid buildup or blood vessel problems related to their liver condition. As an Early Phase 1 trial, this research focuses on understanding how TIPS works in people, offering participants the chance to contribute to groundbreaking medical knowledge.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the TIPS procedure is safe for patients with liver cirrhosis?

Research shows that TIPS (Transjugular Intrahepatic Portosystemic Shunt) is generally a safe treatment for people with liver problems. It helps manage portal hypertension, a serious condition involving high blood pressure in the liver's blood vessels. One study found that TIPS works well and is well-tolerated by patients with liver cirrhosis. While side effects like stent issues or rebleeding can occur, they are uncommon.

Another study found that TIPS is also safe for people with liver cancer. This treatment has been used for a long time, and doctors follow guidelines to ensure its safe use. Although this trial is in its early stages, previous research supports the safety of TIPS in treating liver conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the TIPS procedure for liver cirrhosis and muscle loss because it offers a novel approach to managing complications associated with this condition. Unlike standard treatments, which typically focus on medication and lifestyle changes to manage symptoms, TIPS directly addresses portal hypertension by creating a new pathway for blood flow in the liver. This can potentially reduce the strain on the liver and improve overall function. Additionally, TIPS might help alleviate muscle loss, a common problem in cirrhosis patients, by improving blood flow and nutrient delivery to the muscles. This dual benefit makes TIPS a promising option for those struggling with the challenges of liver cirrhosis.

What evidence suggests that the TIPS procedure is effective for improving muscle mass in liver cirrhosis patients?

Research shows that the TIPS procedure, which participants in this trial may undergo, can help increase muscle and fat in people with liver cirrhosis. Studies have found that patients who undergo TIPS experience improvements in muscle mass and body composition. This is important because muscle loss is a common issue for those with cirrhosis. Improved muscle mass can enhance physical abilities and may benefit patients awaiting a liver transplant. Overall, these findings suggest that TIPS could be beneficial for cirrhotic patients experiencing muscle loss. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-99 with cirrhosis listed for liver transplant, experiencing complications like persistent fluid buildup or bleeding due to portal hypertension. It's not suitable for those with frequent brain function issues from liver disease, severe clotting problems, current infections, pregnancy, urgent need for TIPS, no other treatment options, active cancer outside the liver or a MELD score over 25.

Inclusion Criteria

I need a procedure to open a blocked vein in my liver for a transplant.

I have stomach issues due to liver problems and anemia from bleeding.

I have increased fluid in my abdomen or chest needing more water pills.

Exclusion Criteria

I am unable to make my own medical decisions.

I have had more than one episode of severe confusion due to liver problems.

I have no other treatment options besides TIPS for my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo TIPS creation or continue with standard management to assess body composition changes and clinical outcomes

6 months

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including body composition and clinical outcomes

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Transjugular Intrahepatic Portosystemic Shunt (TIPS) creation

Trial Overview

The study tests if creating a Transjugular Intrahepatic Portosystemic Shunt (TIPS) in cirrhotic patients improves muscle mass and physical function compared to those without TIPS. The goal is to see if these changes lead to better outcomes while waiting for a liver transplant.

How Is the Trial Designed?

Group I: TIPS Experimental Treatment 1 Intervention

Patients in this arm will undergo TIPS creation in addition to their current management.

Group II: Standard of care Active Control 1 Intervention

Patients in this arm will continue to be treated with their current management

Transjugular Intrahepatic Portosystemic Shunt (TIPS) creation is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as TIPS for:

• Refractory ascites
• Variceal bleeding
• Hepatic hydrothorax

Approved in United States as TIPS for:

• Refractory ascites
• Variceal bleeding
• Hepatic hydrothorax

Approved in Canada as TIPS for:

• Refractory ascites
• Variceal bleeding
• Hepatic hydrothorax

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

In a study of 467 patients with cirrhosis undergoing TIPS for variceal bleeding, those with spontaneous portosystemic shunts (SPSSs) experienced similar long-term outcomes and safety profiles compared to those without SPSSs, indicating that TIPS is effective for both groups.

The procedure was safe, with only one case of asymptomatic pulmonary embolism and one case of serious gastric ulcer bleeding in the SPSS group, and overall complication rates were not significantly different between the two groups during a median follow-up of over 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of transjugular intrahepatic portosystemic shunt for treatment of variceal bleeding in patients with cirrhosis with or without spontaneous portosystemic shunt. Leng, X., Zhang, F., Zhang, M., et al.[2020]

In a study of 60 patients who underwent TIPS placement, 19 were non-liver transplant (LT) candidates, and they experienced a significantly higher 2-year mortality rate of 84% compared to 24% for LT candidates, highlighting the severe prognosis for non-LT candidates.

The median survival time for non-LT candidates after TIPS was only 2.6 months, suggesting that while TIPS is a valuable treatment for portal hypertension, its effectiveness in non-LT candidates, particularly those with advanced liver disease (Child-Pugh C class), raises concerns about its appropriateness in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transjugular intrahepatic portosystemic shunt in nonliver transplant candidates: is it indicated? Spiess, SE., Matalon, TA., Jensen, DM., et al.[2006]

Transjugular intrahepatic portal systemic shunt (TIPS) is a safe procedure for managing symptomatic cirrhotic hydrothorax in patients with advanced cirrhosis, as demonstrated in a study of five patients over 11 months with no serious complications reported.

While TIPS effectively reduced the need for thoracentesis in some patients, recurrent pleural effusions were linked to shunt occlusions, which could be treated with angioplasty or urokinase, leading to improved outcomes for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transjugular intrahepatic portal systemic shunt for the management of symptomatic cirrhotic hydrothorax. Strauss, RM., Martin, LG., Kaufman, SL., et al.[2004]

Transjugular intrahepatic portosystemic shunt (TIPS) is a highly effective procedure for controlling variceal bleeding in patients with cirrhosis, with a low complication rate and successful placement in nearly all patients.

While TIPS shows promise for treating complications of portal hypertension, such as ascites, the main challenge remains ensuring the long-term patency of the shunt, which is crucial for sustained effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status and future possibilities of transjugular intrahepatic portosystemic shunts in the management of portal hypertension. Radosevich, PM., LaBerge, JM., Gordon, RL.[2019]

Transjugular intrahepatic portosystemic shunts (TIPS) is a minimally invasive surgical technique that effectively treats portal hypertension, reducing risks associated with general anesthesia and major surgeries.

The first reported case of TIPS in Brazil for a cirrhotic alcoholic patient highlights its potential as a bridge to liver transplantation, improving surgical outcomes and reducing complications like bleeding and the need for blood transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transjugular intrahepatic portosystemic shunts (TIPS) as a bridge for liver transplantation]. de Oliveira e Silva, A., Cardoso, ES., de Melo, CR., et al.[2006]

In a multicenter trial involving 96 patients, transjugular intrahepatic portosystemic shunt (TIPS) placement was successful in all cases, significantly reducing portal pressure and demonstrating high primary (88%) and assisted (94%) patency rates at 6 months.

While TIPS placement is effective for treating portal hypertension, it carries some risks, including complications like increased encephalopathy and varying mortality rates based on liver function class, with 0% mortality in Child-Pugh class A, 18% in class B, and 40% in class C.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter investigation of the role of transjugular intrahepatic portosystemic shunt in management of portal hypertension. Coldwell, DM., Ring, EJ., Rees, CR., et al.[2006]

The transjugular intrahepatic portosystemic shunt (TIPS) procedure was successfully performed on nine patients with cirrhosis and recurrent variceal hemorrhage, effectively reducing the portosystemic gradient from 22.4 mm Hg to 9.7 mm Hg.

All patients survived without any recurrence of variceal hemorrhage after the procedure, indicating that TIPS may be a safe and effective alternative to traditional surgical methods for managing variceal bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transjugular intrahepatic portosystemic shunt (TIPS): a promising nonsurgical treatment for bleeding gastroesophageal varices. Tytle, TL., Loeffler, C., Thompson, WM.[2016]

In a study of 288 patients with advanced liver cirrhosis (MELD score ≥15), those who underwent transjugular intrahepatic porto-systemic shunt (TIPS) showed a 56% lower risk of dying or needing a liver transplant after 2 months compared to those who did not undergo the procedure.

Although there was a trend towards increased mortality or transplantation in the first 2 months post-TIPS, this did not reach statistical significance, suggesting that TIPS may be safe and beneficial for improving long-term survival in selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transjugular Intrahepatic Porto-Systemic Shunt in Patients with Liver Cirrhosis and Model for End-Stage Liver Disease ≥15. Ascha, M., Hanouneh, M., S Ascha, M., et al.[2018]

The transjugular intrahepatic portosystemic shunt (TIPS) procedure has a high technical success rate of 95% and effectively prevents rebleeding from esophageal varices, showing clinical improvement in 93% of patients.

While TIPS carries a lower risk than surgical alternatives and has no immediate mortality, 17% of patients experienced encephalopathy requiring treatment, indicating the need for careful monitoring post-procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[First experience with transjugular intrahepatic porto-systemic shunt (TIPS)]. Lázár, I., Petó, J., Kristóf, T.[2006]

In a study of 100 patients with symptomatic portal hypertension, TIPS (transjugular intrahepatic portosystemic shunt) effectively reduced portal vein pressure, with a primary patency rate of 85% at 6 months and 72% at 12 months.

The main complication associated with TIPS was shunt stenosis, which occurred due to neointimal hyperplasia, but this can be treated effectively with percutaneous balloon angioplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of symptomatic portal hypertension]. Krajina, A., Hůlek, P., Eliás, P., et al.[2006]

In a study of 15 patients with Budd-Chiari syndrome (BCS) undergoing transjugular intrahepatic portosystemic shunt (TIPS), 14 had successful placement, but mortality was high among those with hepatic failure, with four out of eight patients dying shortly after the procedure.

For patients with chronic BCS, TIPS led to significant improvements in liver function and resolution of ascites over an average follow-up of 20 months, suggesting it is an effective treatment for those not responding to medical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIPS for acute and chronic Budd-Chiari syndrome: a single-centre experience. Mancuso, A., Fung, K., Mela, M., et al.[2022]

In a study of 25 cirrhotic patients with a patent TIPS undergoing major surgery, portal decompression significantly reduced hepatic venous pressure, which is crucial for managing complications related to liver disease.

The results suggest that TIPS can enable selected cirrhotic patients to safely undergo major surgeries, with a 1-year survival rate of 74% and manageable short-term complications, particularly in patients with lower MELD scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cirrhotic patients with a transjugular intrahepatic portosystemic shunt undergoing major extrahepatic surgery. Kim, JJ., Dasika, NL., Yu, E., et al.[2014]

Citations

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Sarcopenia as a Risk Factor in Patients Undergoing ...

Sarcopenia Is Risk Factor for Development of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Placement. Clin ...

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Sarcopenia in Patients with Cirrhosis after Transjugular ...

In patients with sarcopenia, both skeletal muscle and fat mass increased after transjugular intrahepatic portosystemic shunt placement.

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sciencedirect.com

sciencedirect.com/science/article/pii/S092966462300061X

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Another recent study indicated that TIPS placement is strongly associated with changes in trunk muscle mass in patients with cirrhosis. These results indicate ...

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Sarcopenia Associated With Risk for Complications ...

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This retrospective study highlights a high prevalence. (50%) of sarcopenia in patients with cirrhosis at the time of undergoing the transjugular intrahepatic ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3992326/

Clinical outcomes of transjugular intrahepatic ...

Twenty-eight (93.3%) patients with variceal rebleeding had stent dysfunction. The overall rebleeding rate after TIPS placement was 21.1 and 16.7% in the ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7545393/

Transjugular intrahepatic portosystemic shunt in cirrhosis

The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0009926022006717

Safety and effectiveness of transjugular intrahepatic ...

TIPS is a safe and effective treatment in HCC patients. Portal vein tumour thrombosis (PVTT) and cavernous transformation are the major cause of procedural ...

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clinicaltrials.gov/study/NCT06576934

Early TIPS in Patients With Liver Cirrhosis and Ascites

Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) has emerged as a safe and effective interventional treatment of portal hypertension. TIPS ...

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journal-of-hepatology.eu

journal-of-hepatology.eu/article/S0168-8278(25)00066-2/abstract

EASL Clinical Practice Guidelines on TIPS

The aim of these EASL guidelines is to comprehensively address all aspects of TIPS in patients with cirrhosis.