Final safety and efficacy results from a 106 real-world patients registry with an ascites-mobilizing pump

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Results: Approximately half of the patients died on-study, about a quarter was withdrawn because of serious adverse events leading to explant, a sixth were withdrawn because of liver transplant or recovery, and nine completed follow-up.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).

Keywords: TIPSS; alfapump; ascites; cirrhosis; large-volume paracentesis.

Conflict of interest statement

GS has received support for the present manuscript, travel and meeting attendance, served as a speaker and participated in Advisory Boards for Sequana Medical. TB has received grants or contracts with Abbvie, BMS, Gilead, Humedics, Intercept, MSD/Merck, Merz, Novartis and Sequana Medical, received consulting fees from Abbvie, Alexion, Bayer, Eisai, Gilead, GSK, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Roche, Sequana Medical and Shionogi and served as a speaker for MedUpdate GmbH and the abovementioned except GSK, Roche and Shionogi, He has received support for travel and meeting attendance from Abbvie, Gilead, Intercept and Janssen. LS has received lecture honoraria from and participated in Advisory Boards of Sequana Medical. SZ has served as a speaker and a consultant to Abbvie, Gilead, Intercept, Janssen, Merck/MSD. SMP has served as a consultant to Sequana Medical, AbbVie, Gilead, Cambwick and Intercept. FS has served as a speaker to Sequana Medical. CE has received research grants from Sequana Medical, the German Research Foundation (DFG) and the Berlin Institute of Health (BIH). AG has received consulting fees from Abbvie, Alexion, Bayer, BMS, CSL Behring, Eisai, Gilead, Intercept, Ipsen, Merz MSD, Novartis, Pfizer, Roche, Sanofi‐Aventis and Sequana Medical, received support for meeting attendance and travel from Abbvie, Gilead, Intercept and Merz and participated on a Data Safety Monitoring Board or Advisory Board for Novartis. CT is a biostatistician contracted by Sequana Medical. JC is an employee of and holds shares and stock options of Sequana Medical. ADG has received a research grant from Sequana Medical. FL, JB, VV and VB have nothing to disclose.

© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Survival of patients and device components. (A) Time to first pump exchange or explant because of device deficiency. Death, withdrawal for reasons unrelated to the device and explants because of orthotopic liver transplantation or resolution of ascites were censored at the time of explant or death as appropriate. (B) Overall survival including known deaths after pump explant. Withdrawal and study completion were censored at the time of explant. (C) Survival of the first 50 (blue) versus the last 50 patients enrolled (red) including known deaths after pump explant, withdrawal and study completion. The p‐value was calculated using the Mantel‐Cox test. (D) Time to peritoneal catheter deficiency in the standard (blue, n = 111) versus modified catheter (red; n = 16), showing a significantly longer lifetime for the latter. The p‐value was calculated using the Breslow (Generalized Wilcoxon) test. All panels: Vertical lines indicate censoring of patients at risk. Dashed lines represent 95% confidence interval boundaries.

FIGURE 2

Paracentesis (A) Pre‐ versus post‐implant paracentesis frequency per month and (B) volume of ascites (L) evacuated per month 3 months pre‐implant versus post‐implant. Note that pre‐implant values are estimates based on data collected at the baseline visit and that post‐implant values may be underestimated because not all paracenteses may have become known. Hence, a formal p‐value was not calculated. Mean is indicated with +. Bars represent median and interquartile range; whiskers indicate 5th and 95th percentile. (C) Large‐volume paracentesis (>5 L) post‐implant.

FIGURE 3

Mean changes of liver scores and lab values of interest from baseline. (A) Model of end‐stage liver disease (MELD) score (United Network of Organ Sharing [UNOS]), (B) Child‐Pugh Score, (C) serum albumin, (D) total bilirubin and (E) international normalized ratio (INR), (F) serum creatinine versus baseline over time. Blue: Total patient population. Red: Short‐term patients (withdrawn at