Final Safety and Efficacy Results From a 106 Real-world Patients Registry With an Ascites-mobilizing Pump

Guido Stirnimann; Thomas Berg; Laurent Spahr; Stefan Zeuzem; Stuart McPherson; Frank Lammert; Federico Storni; Vanessa Banz; Jana Babatz; Victor Vargas; Andreas Geier; Cornelius Engelmann; Adam Herber; Claudia Trepte; Jeroen Capel; Andrea De Gottardi

Disclosures

Liver International. 2022;42(10):2247-2259. 

In This Article

Abstract and Introduction

Abstract

Background and Aims: Patients with cirrhotic refractory ascites ineligible for transjugular intrahepatic shunt (TIPSS) have limited treatment options apart from repeated large volume paracentesis. The alfapump® is an implantable device mobilizing ascites from the peritoneal cavity to the bladder, from where it can be excreted. The aim of this observational cohort study was to prospectively investigate safety and efficacy of the device in a real-world cohort with cirrhotic refractory ascites and contraindications for TIPSS.

Methods: A total of 106 patients received an implant at 12 European centres and were followed up for up to 24 months. Complications, device deficiencies, frequency of paracentesis, clinical status and survival were recorded prospectively.

Results: Approximately half of the patients died on-study, about a quarter was withdrawn because of serious adverse events leading to explant, a sixth were withdrawn because of liver transplant or recovery, and nine completed follow-up. The most frequent causes of on-study death and complication-related explant were progression of liver disease and infection. The device reduced the requirement for large-volume paracentesis significantly, with more than half of patients not having required any post-implant. Survival benefits were not observed. Device-related reinterventions were predominantly caused by device deficiencies. A post-hoc comparison of the first 50 versus the last 50 patients enrolled revealed a decreased reintervention rate in the latter, mainly related to peritoneal catheter modifications.

Conclusions: The device reduced paracentesis frequency in a real-world setting. Technical complications were successfully decreased by optimization of management and device modification (NCT01532427).

Introduction

Ascites is the accumulation of fluid in the peritoneal cavity secondary to portal hypertension and compensatory circulatory reactions in patients with advanced liver cirrhosis. Five to ten per cent of patients with ascites develop refractory ascites (RA) per year,[1,2] that is, ascites which cannot be controlled any longer by standard treatment strategies such as dietary limitation of sodium uptake combined with high-dose diuretics. This is either because the highest-possible diuretic dose failed to prevent ascites re-accumulation or the patient developed adverse events contraindicating further use. Prognosis of RA is poor, with approximately a third of patients dying within 6 months[3] unless salvaged by liver transplant, which is currently the only curative treatment. Standard of care (SoC) for RA is repeated large-volume paracentesis (LVP), defined by mobilization of >5000 ml of volume in one paracentesis, and albumin substitution to prevent circulatory dysfunction.[4] Repeated LVP is relatively safe but represents a considerable burden in terms of healthcare resources and compromises quality of life (QoL) of the patient because of discomfort and frequent hospitalization.

Alternatively, RA may be treated by insertion of a Transjugular Intrahepatic Portosystemic Shunt (TIPSS), which releases some of the pressure in the portal venous system.[3] However, TIPSS is only suitable for a subset of patients free from comorbidities such as congestive heart failure, pulmonary hypertension or cirrhosis-related complications, e.g., advanced stage and episodes of recurrent overt hepatic encephalopathy (HE) without an identifiable precipitating factor.[3–5]

The alfapump® system (Sequana Medical N.V.) is a subcutaneously implanted medical device consisting of a pump unit and two silicone catheters. It is designed to transport ascitic fluid from the peritoneal cavity into the bladder. Ascites is excreted with urine, thereby reducing the requirement for paracentesis. Pump activity can be modified by the treating physician according to individual clinical needs.[6] The device received European market approval in 2011 based on clinical data obtained in the PIONEER study[7] which included 40 patients followed up for mean 124 ± 57 days. This current study was initiated in 2012 to prospectively collect clinical data related to safety and performance of the device in a cohort of patients ineligible for TIPSS in a real-world setting with a follow-up of up to 24 months or until withdrawal or death. Studies published in the meantime, including a meta-analysis and an interim analysis of this current registry comprising the first 56 patients, confirmed a significant reduction of LVP and paracentesis compared to the pre-implant period or SoC[8–11] and reported improvement of QoL[8,9,12] and nutritional status.[8,9] However, despite modifications of the device and manufacturer's instructions, high rates of adverse events and technical issues requiring reintervention were observed.[11] Frequent safety-related issues include deterioration of kidney function (acute kidney injury [AKI], increase in serum creatinine [sCr][8,10,13]) and infections (pump pocket infections, spontaneous bacterial peritonitis [SBP], urinary tract infections [UTI]). Infections occurred at rates of 0.5 per patient in 12 months to 0.93 per patient in 6 months.[9,14] The most important cause of reinterventions and explants, the latter required in approximately 20–30%, were infections and peritoneal catheter (PC) issues.[10,11] Survival benefits compared to SoC were not observed.[8] The primary objective of this study was to evaluate safety by prospectively recording device-related incidents in a real-world setting. The secondary objective was to evaluate clinical performance (post-implant paracentesis requirement, patients' clinical status by evolution of liver scores and relevant laboratory parameters). Here, final results from the full cohort of 106 patients included in this registry observed during 6 years are presented and discussed in relation to currently available clinical data.

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