Ascites, Hypertension, Portal, Liver Cirrhosis
Conditions
Keywords
Refractory Ascites, Decompensated Cirrhosis, Proximal Splenic Artery Embolization, Splenic Artery Embolization, Large Volume Paracentesis, Trans Jugular Intrahepatic Portosystemic Shunt, Hepatic Venous Pressure Gradient
Brief summary
The purpose of this study is to learn whether a procedure called Proximal Splenic Artery Embolization (PSAE) can lower the need for repeat fluid drainage in adults with cirrhosis and a buildup of fluid in the abdomen (ascites) that is no longer controlled by water pills and diet. Participants in this study have already been told that a standard procedure called Trans jugular Intrahepatic Portosystemic Shunt (TIPS) is not a safe option for them. The main objectives this study aims to answer are: * Does PSAE lower how often participants need paracentesis, the procedure used to drain fluid from the abdomen? * Does PSAE lower the total amount of fluid drained each month? * Does PSAE change the pressure inside the liver's veins and the blood flow in the liver and spleen? * Does PSAE improve day-to-day symptoms, quality of life, strength, and the ability to do usual activities? * What side effects or complications happen with PSAE in this group of people? Participants will: * Undergo one PSAE procedure, during which small coils and/or plugs are placed in the artery that supplies the spleen to slow its blood flow * Have a pressure measurement taken in the liver's veins right before and right after the procedure, with a repeat measurement at 1 month * Attend follow-up visits at 1, 3, and 6 months that include blood tests, ultrasounds, symptoms and quality-of-life questionnaires, and a review of any paracentesis sessions since the last visit * Have a Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) and an ultrasound of the liver and spleen blood vessels at the start of the study and again at 6 months
Detailed description
Refractory ascites is a common complication of decompensated cirrhosis and carries a substantial symptom burden and reduced quality of life. Standard management includes repeated large-volume paracentesis and, for eligible candidates, placement of TIPS. TIPS is effective for many patients but carries a meaningful risk of hepatic decompensation, new or worsening hepatic encephalopathy and is not a safe option for patients with a high Model for End-Stage Liver Disease (MELD) score, prior encephalopathy, cardiac dysfunction, or unfavorable vascular anatomy. PSAE is a catheter-based procedure in which coils and/or vascular plugs are placed in the proximal splenic artery to reduce arterial blood flow to the spleen while preserving splenic viability through collateral vessels. By lowering splenic blood flow into the portal venous system, PSAE is expected to reduce portal pressure and the driving force behind ascites formation, without creating a new vascular connection that could trigger hepatic encephalopathy. This is a prospective, multi-center, single-arm, open-label study. Eligible participants undergo a single PSAE procedure, with Hepatic Venous Pressure Gradient (HVPG) measurement performed immediately before and after embolization, followed by 6 months of structured follow-up including laboratory testing, imaging, and patient-reported assessments. An independent Data Safety Monitoring Board (DSMB) reviews safety data at pre-specified intervals throughout the study. The co-primary effectiveness endpoints are the change from baseline to Month 6 in the average monthly number of large-volume paracentesis sessions and the change in the average monthly volume of ascitic fluid drained. The primary safety endpoint is the proportion of participants who experience a major procedure-related adverse event within 6 months of PSAE. Secondary endpoints include change in HVPG, hepatic artery resistive index by Doppler ultrasound, diuretic dose, and time to resolution of paracentesis dependence. Additional assessments capture patient-reported symptom burden and quality of life, physical frailty, hepatic encephalopathy grading, laboratory measures of liver and kidney function, and body composition by CT.
Interventions
DEVICEProximal Splenic Artery Embolization
A one-time transcatheter arterial procedure performed under moderate sedation or monitored anesthesia care. Common femoral arterial access is obtained under ultrasound guidance, and a catheter is advanced into the splenic artery. Embolic coils and/or vascular plugs, cleared for peripheral vascular embolization, are deployed to achieve angiographic cessation of antegrade flow in the proximal splenic artery, while collateral flow to the spleen is preserved. Oral antibiotic prophylaxis is given for 7 days following the procedure.
Sponsors
Massachusetts General Hospital
National Institutes of Health (NIH)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years at the time of informed consent. * Decompensated cirrhosis confirmed by clinical, laboratory, radiographic, or histologic criteria. * Portal hypertension of sinusoidal origin. Pre-sinusoidal (e.g., idiopathic non-cirrhotic portal hypertension, schistosomiasis) and post-sinusoidal (e.g., Budd-Chiari syndrome, right-heart failure, constrictive pericarditis) etiologies are excluded. * Refractory or recurrent ascites defined as ascites not controlled by maximum tolerated diuretic therapy (spironolactone ≤ 400 mg/day + furosemide ≤ 160 mg/day, or maximum tolerated doses below these limits) and sodium restriction, or diuretic-intractable due to diuretic-induced complications. * Demonstrated large-volume paracentesis (LVP) dependence for ≥ 3 consecutive months prior to screening, with ≥ 2 LVP sessions per month on average during that window, documented in the institutional medical record or in external paracentesis procedure records released to the investigator. * Ineligible or relatively contraindicated for TIPS. Acceptable reasons include but are not limited to: MELD-Na \> 18 with additional risk factors, pre-existing or recurrent overt hepatic encephalopathy, advanced age with comorbidity, clinically significant cardiopulmonary disease, or anatomic contraindication. * Life expectancy ≥ 6 months in the judgment of the enrolling investigator. * Able and willing to provide written informed consent and to adhere to the study visit and assessment schedule. * Abdominal cross-sectional imaging (CT or MRI) within 60 days of enrollment confirming patency of the main portal vein and main splenic vein, and absence of findings that would contraindicate PSAE.
Exclusion criteria
* Age \< 18 years. * Unable to provide informed consent and without an appropriate legally authorized representative. * Pre-sinusoidal or post-sinusoidal portal hypertension (e.g., extrahepatic portal vein thrombosis, idiopathic non-cirrhotic portal hypertension, schistosomiasis, Budd-Chiari syndrome, hepatic sinusoidal obstruction syndrome, constrictive pericarditis, right-heart failure). * Main portal vein thrombosis, splenic vein thrombosis, or superior mesenteric vein thrombosis on screening imaging. * Active listing for liver transplantation with MELD-Na ≥ 20 at screening, or any listing status in which transplantation within 6 months is judged highly likely by the site transplant team. (Listed participants with MELD-Na \< 20 and low anticipated short-term transplant probability may be enrolled with documented site transplant-team concurrence.) * Pre-existing splenectomy, prior distal splenic artery embolization, or pre-existing splenic abscess, large splenic infarction (≥ 30% of splenic parenchyma), or splenic mass on imaging. * Active or uncontrolled systemic infection, including spontaneous bacterial peritonitis in the prior 14 days, bacteremia in the prior 14 days, or any infection requiring parenteral antibiotics at the time of screening. * Active gastrointestinal bleeding within 14 days, or untreated high-risk esophageal or gastric varices (primary prophylaxis not yet established) - treatable prior to enrollment. * Severe coagulopathy not correctable to INR ≤ 2.0 and platelets ≥ 30 × 10⁹/L on the day of the procedure. * Known severe allergy to iodinated contrast not manageable with standard pre-medication, or contrast contraindication precluding cross-sectional CT imaging. * eGFR \< 30 mL/min/1.73 m² not on renal replacement therapy, unless iodinated contrast use can be minimized per site protocol and nephrology concurrence is documented. * Pregnancy or breastfeeding. Participants of childbearing potential must have a negative serum pregnancy test at screening and agree to effective contraception through Month 6. * Hepatocellular carcinoma beyond BCLC Stage A, or any active extrahepatic malignancy with life expectancy \< 6 months. * Active substance use disorder other than alcohol or tobacco that, in the investigator's judgment, would preclude protocol adherence. Active alcohol use disorder is not exclusionary but is captured (AUDIT-C) and analyzed as a pre-specified covariate. * Enrollment in another interventional clinical trial within 30 days or concurrent with this study that could confound endpoints, including TIPS-related trials. * Any medical, psychiatric, or social condition that in the investigator's judgment would preclude safe participation or adherence to the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Monthly Frequency of Large-Volume Paracentesis Sessions | Baseline (3-month period ending on day of PSAE) to Month 6 post-PSAE | Change from the mean monthly number of large-volume paracentesis (LVP) sessions during the 3-month period before PSAE to the number of sessions in the 28-day window ending at the Month 6 visit, abstracted from clinical and procedural records. |
| Change in Monthly Volume of Ascites Fluid Drained | Baseline (3-month period ending on day of PSAE) to Month 6 post-PSAE | Change from the mean monthly total volume (in liters) of ascites fluid drained during the 3-month period before PSAE to the total volume drained in the 28-day window ending at the Month-6 visit, abstracted from clinical and procedural records |
| Proportion of Participants with a Major Procedure-Related Adverse Event | Within 6 months of PSAE | Proportion of participants experiencing at least one procedure-related adverse event graded Society of Interventional Radiology (SIR) Adverse Event Classification System (2017) grade 3 or higher, cross-referenced to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 grading |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hepatic Venous Pressure Gradient at Month 1 | Day 0 (pre-embolization) to Month 1 post PSAE | Change in HVPG, measured in mmHg by trans jugular catheterization and calculated as wedged hepatic venous pressure minus free hepatic venous pressure, from the pre-embolization measurement on the day of PSAE to the Month-1 follow-up measurement |
| Change in Hepatic Artery Resistive Index (RI) | Baseline to Month 1 post-PSAE | Change in hepatic artery resistive index, measured by Doppler ultrasound and calculated as (difference between peak systolic velocity and end-diastolic velocity) divided by peak systolic velocity |
| Change in Daily Diuretic Dose | Baseline to Month 6 post-PSAE | Change in daily diuretic dose, expressed in spironolactone-equivalent and furosemide-equivalent units |
| Time to Resolution of Large-Volume Paracentesis Dependence | From PSAE up to Month 6 | Time from PSAE to the first 60-day interval without a large-volume paracentesis session, analyzed with death and liver transplantation treated as competing events |
| Acute Change in HPVG | Day 0 (pre-procedure to immediately post-procedure) | Change in HPVG, measured in mmHg, from immediately before to immediately after the PSAE procedure |
| Change in Portal-Venous Flow Velocity | Baseline to Month 1 | Change in main portal vein blood flow velocity, measured by Doppler ultrasound |
| Change in Splenic-Venous Flow Velocity | Baseline to Month 1 | Change in splenic venous flow velocity, measured by Doppler ultrasound |
| Rate of Unplanned Hospital admissions and Emergency Department visits related to Portal Hypertension Complications | Over 6 months | Rate and cumulative incidence of unplanned hospital admissions and emergency department visits attributed to spontaneous bacterial peritonitis, hyponatremia, acute kidney injury, hepatic encephalopathy, or gastrointestinal variceal bleeding |
| Incidence of Hepatic Encephalopathy Episodes | Over 6 months | Number of participants experiencing at least one hepatic encephalopathy episode |
| Severity of Hepatic Encephalopathy Episodes | Over 6 months | Severity of hepatic encephalopathy episodes, graded using the West Haven criteria (Grade 0 to Grade 4, with higher grades indicating more severe encephalopathy) |
| Duration of Hepatic Encephalopathy Episodes | Over 6 months | Duration, in days, of hepatic encephalopathy episodes |
| Change in Number Connection Test performance | Baseline to Months 1, 3, and 6 | Change in Number Connection Test score, a timed psychometric test for covert hepatic encephalopathy; longer compeltion time indicates worse performance |
| Change in Serum Creatinine | Baseline to Months 1, 3, and 6 | Change in Serum Creatinine level |
| Change in Estimated Glomerular Filtration Rate (eGFR) | Baseline to Months 1,3, and 6 | Change in eGFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation |
| Change in Model for End-Stage Liver Disease-Sodium (MELD-Na) Score | Baseline to Months 1,3, and 6 | Change in Model for End-Stage Liver Disease-Sodium (MELD-Na) Score, calculated using the Organ Procurement and Transplantation Network (OPTN)-specified formula in effect at the time of enrollment |
| Transplant-Free Survival | Over 6 Months | Time from PSAE to death, with liver transplantation treated as a competing event |
| Proportion of Participants Achieving Large-Volume Paracentesis Independence | At Months 1,3, and 6 | Proportion of participants who reach a 60-day interval without a large-volume paracentesis session, assessed at each visit |
| Change in Child-Pugh Score | Baseline to Months 1,3, and 6 | Change in Child-Pugh Score, calculated from total bilirubin, serum albumin, Internation Normalized Ratio (INR), degree of ascites, and degree of hepatic encephalopathy |
| Change in Child-Pugh Class | Baseline to Months 1,3, and 6 | Change in Child-Pugh Class (Class A, 5-6 points, Class B, 7-9 points; Class C, 10-15 points) |
Countries
United States
Contacts
CONTACTEric P. Wehrenberg-Klee, MD
CONTACTPooja Ramakrishnan, MS
PRINCIPAL_INVESTIGATOREric P. Wehrenberg-Klee, MD
Massachusetts General Hospital
Outcome results
None listed