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

Trial Summary

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 data supports the effectiveness of the TIPS treatment for liver cirrhosis and muscle loss?

TIPS is effective in treating complications of severe portal hypertension, such as variceal bleeding, and has a high technical success rate with most patients showing clinical improvement. It is also used in managing conditions like Budd-Chiari syndrome and has a low complication rate, although long-term shunt patency remains a concern. ^{1 2 3 4 5}

Is the TIPS procedure generally safe for humans?

The TIPS procedure is generally considered safe, with a high technical success rate and clinical improvement in most patients. However, some complications can occur, such as encephalopathy (a brain condition that affects thinking and behavior), and there is a risk of mortality, especially in patients with severe liver disease. ^{1 6 7 8 9}

How does the TIPS procedure differ from other treatments for liver cirrhosis and muscle loss?

The TIPS procedure is unique because it is a minimally invasive treatment that creates a shunt (a passage) inside the liver to reduce high blood pressure in the portal vein, which can help prevent complications like bleeding and fluid buildup. Unlike traditional surgery, it avoids the risks of general anesthesia and major surgery, making it a safer option for patients with liver cirrhosis. ^{1 2 10 11 12}

What is the purpose of this trial?

The purpose of this study is to prospectively assess the impact of TIPS creation on muscle mass and physical function in patients with cirrhosis, and to determine whether these changes correlate with improved outcomes in patients awaiting liver transplantation. Retrospective observational studies have shown improvement in muscle mass and body composition in cirrhotic patients undergoing TIPS. The investigators aim to now prospectively study this through a pilot randomized controlled trial tracking patients managed with TIPS creation compared to those managed without TIPS to determine whether these observational findings can be seen in a randomized cohort. The investigators hypothesize that TIPS creation will lead to improved muscle mass, body composition and muscle function within the first 12 months after the procedure compared to a control group without TIPS, and that these changes will improve liver disease outcomes in patients awaiting liver transplantation.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

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]

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]

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 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 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]

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]

References

1. Hungary pubmed.ncbi.nlm.nih.gov

[First experience with transjugular intrahepatic porto-systemic shunt (TIPS)]. [2006]

2. United States pubmed.ncbi.nlm.nih.gov

Transjugular intrahepatic portosystemic shunt in nonliver transplant candidates: is it indicated? [2006]

3. United States pubmed.ncbi.nlm.nih.gov

Current status and future possibilities of transjugular intrahepatic portosystemic shunts in the management of portal hypertension. [2019]

4. Czech Republic pubmed.ncbi.nlm.nih.gov

[Transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of symptomatic portal hypertension]. [2006]

5. Netherlands pubmed.ncbi.nlm.nih.gov

TIPS for acute and chronic Budd-Chiari syndrome: a single-centre experience. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Transjugular Intrahepatic Porto-Systemic Shunt in Patients with Liver Cirrhosis and Model for End-Stage Liver Disease ≥15. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Multicenter investigation of the role of transjugular intrahepatic portosystemic shunt in management of portal hypertension. [2006]

8. England 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. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Transjugular intrahepatic portal systemic shunt for the management of symptomatic cirrhotic hydrothorax. [2004]

10. Brazil pubmed.ncbi.nlm.nih.gov

[Transjugular intrahepatic portosystemic shunts (TIPS) as a bridge for liver transplantation]. [2006]

11. United States pubmed.ncbi.nlm.nih.gov

Cirrhotic patients with a transjugular intrahepatic portosystemic shunt undergoing major extrahepatic surgery. [2014]

12. United States pubmed.ncbi.nlm.nih.gov

Transjugular intrahepatic portosystemic shunt (TIPS): a promising nonsurgical treatment for bleeding gastroesophageal varices. [2016]