A Prospective, Multi-Center, Single-Arm Clinical Study of Proximal Splenic Artery Embolization (PSAE) for the Treatment of Refractory Ascites in Decompensated Cirrhosis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Change in Monthly Frequency of Large-Volume Paracentesis Sessions
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Proximal Splenic Artery Embolization
All enrolled participants undergo a single PSAE procedure. Small embolization 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. HVPG is measured immediately before and after embolization. Oral antibiotic prophylaxis is given for 7 days following the procedure. Participants are followed for 6 months after PSAE, during which paracentesis records, laboratory data, imaging, and patient-reported outcomes are collected.
干预措施: Proximal Splenic Artery Embolization (Device)
结局指标
主要结局
Change in Monthly Frequency of Large-Volume Paracentesis Sessions
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- Change in Estimated Glomerular Filtration Rate (eGFR)(Baseline to Months 1,3, and 6)
- Change in Portal-Venous Flow Velocity(Baseline to Month 1)
- Change in Splenic-Venous Flow Velocity(Baseline to Month 1)
- Change in Serum Creatinine(Baseline to Months 1, 3, and 6)
- Change in Hepatic Venous Pressure Gradient at Month 1(Day 0 (pre-embolization) to Month 1 post PSAE)
- Change in Hepatic Artery Resistive Index (RI)(Baseline to Month 1 post-PSAE)
- Change in Daily Diuretic Dose(Baseline to Month 6 post-PSAE)
- Time to Resolution of Large-Volume Paracentesis Dependence(From PSAE up to Month 6)
- Acute Change in HPVG(Day 0 (pre-procedure to immediately post-procedure))
- Rate of Unplanned Hospital admissions and Emergency Department visits related to Portal Hypertension Complications(Over 6 months)
- Incidence of Hepatic Encephalopathy Episodes(Over 6 months)
- Severity of Hepatic Encephalopathy Episodes(Over 6 months)
- Duration of Hepatic Encephalopathy Episodes(Over 6 months)
- Change in Number Connection Test performance(Baseline to Months 1, 3, and 6)
- Change in Model for End-Stage Liver Disease-Sodium (MELD-Na) Score(Baseline to Months 1,3, and 6)
- Transplant-Free Survival(Over 6 Months)
- Proportion of Participants Achieving Large-Volume Paracentesis Independence(At Months 1,3, and 6)
- Change in Child-Pugh Score(Baseline to Months 1,3, and 6)
- Change in Child-Pugh Class(Baseline to Months 1,3, and 6)
研究者
Eric Wehrenberg-Klee, MD
Interventional Radiologist
Massachusetts General Hospital