Christophe Bureau1, Danielle Adebayo2, Mael Chalret de Rieu1, Laure Elkrief3, Dominique Valla3, Markus Peck-Radosavljevic4, Anne McCune5, Victor Vargas6, Macarena Simon-Talero6, Juan Cordoba6, Paolo Angeli7, Silvia Rosi7, Stewart MacDonald2, Massimo Malago8, Maria Stepanova9, Zobair M Younossi10, Claudia Trepte11, Randall Watson12, Oleg Borisenko13, Sun Sun14, Neil Inhaber11, Rajiv Jalan15. 1. Service d'hépato-gastroentérologie, CHU Toulouse, Toulouse, France. 2. UCL Institute of Hepatology, Royal Free Hospital, University College London, London, United Kingdom. 3. DHU UNITY, Service d'hépatologie, Hôpital Beaujon, Clichy and Université Paris Diderot and Inserm U1149, Paris, France. 4. Department of Gastroenterology/Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria. 5. Department of Hepatology, Bristol Royal Infirmary, Bristol, United Kingdom. 6. Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, VHIR, Universitat Autònoma de Barcelona, CIBERehd, Barcelona, Spain. 7. Facoltà di Medicina e Chirurgia, Università degli Studi di Padova, Padova, Italy. 8. Hepato-pancreatic-biliary and Liver Transplantation Surgery, Royal Free Hospital, University College London, London, United Kingdom. 9. Center for Outcomes Research in Liver Disease, Washington DC, United States. 10. Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, United States. 11. Sequana Medical AG, Zurich, Switzerland. 12. Medicalwriters.com, Zurich, Switzerland. 13. Synergus AB, Danderyd, Sweden. 14. Synergus AB, Danderyd, Sweden; Health Outcomes and Economic Evaluation Research Group, Department of Learning, Information, Management and Ethics, Karolinska Institutet, Stockholm, Sweden; Division of Epidemiology and Global Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 15. UCL Institute of Hepatology, Royal Free Hospital, University College London, London, United Kingdom. Electronic address: r.jalan@ucl.ac.uk.
Abstract
BACKGROUND AND AIMS: Patients with refractory ascites (RA) require repeated large volume paracenteses (LVP), which involves frequent hospital visits and is associated with a poor quality-of-life. This study assessed safety and efficacy of an automated, low-flow pump (alfapump® [AP]) compared with LVP standard of care [SoC]. METHODS: A randomized controlled trial, in seven centers, with six month patient observation was conducted. Primary outcome was time to first LVP. Secondary outcomes included paracentesis requirement, safety, health-related quality-of-life (HRQoL), and survival. Nutrition, hemodynamics, and renal injury biomarkers were assessed in a sub-study at three months. RESULTS:Sixty patients were randomized and 58 were analyzed (27 AP, 31 SoC, mean age 61.9years, mean MELD 11.7). Eighteen patients were included in the sub-study. Compared with SoC, median time to first LVP was not reached after six months in the AP group, meaning a significant reduction in LVP requirement for the AP patients (AP, median not reached; SoC, 15.0days (HR 0.13; 95%CI 13.0-22.0; p<0.001), and AP patients also showed significantly improved Chronic Liver Disease Questionnaire (CLDQ) scores compared with SoC patients (p<0.05 between treatment arms). Improvements in nutritional parameters were observed for hand-grip strength (p=0.044) and body mass index (p<0.001) in the sub-study. Compared with SoC, more AP patients reported adverse events (AEs; 96.3% vs. 77.4%, p=0.057) and serious AEs (85.2 vs. 45.2%, p=0.002). AEs consisted predominantly of acute kidney injury in the immediate post-operative period, and re-intervention for pump related issues, and were treatable in most cases. Survival was similar in AP and SoC. CONCLUSIONS: The AP system is effective for reducing the need for paracentesis and improving quality of life in cirrhotic patients with RA. Although the frequency of SAEs (and by inference hospitalizations) was significantly higher in the AP group, they were generally limited and did not impact survival. Lay summary: The alfapump® moves abdominal fluid into the bladder from where it is then removed by urination. Compared with standard treatment, the alfapump reduces the need for large volume paracentesis (manual fluid removal by needle) in patients with medically untreatable ascites. This can improve life quality for these patients. www.clinicaltrials.gov#NCT01528410.
RCT Entities:
BACKGROUND AND AIMS: Patients with refractory ascites (RA) require repeated large volume paracenteses (LVP), which involves frequent hospital visits and is associated with a poor quality-of-life. This study assessed safety and efficacy of an automated, low-flow pump (alfapump® [AP]) compared with LVP standard of care [SoC]. METHODS: A randomized controlled trial, in seven centers, with six month patient observation was conducted. Primary outcome was time to first LVP. Secondary outcomes included paracentesis requirement, safety, health-related quality-of-life (HRQoL), and survival. Nutrition, hemodynamics, and renal injury biomarkers were assessed in a sub-study at three months. RESULTS: Sixty patients were randomized and 58 were analyzed (27 AP, 31 SoC, mean age 61.9years, mean MELD 11.7). Eighteen patients were included in the sub-study. Compared with SoC, median time to first LVP was not reached after six months in the AP group, meaning a significant reduction in LVP requirement for the AP patients (AP, median not reached; SoC, 15.0days (HR 0.13; 95%CI 13.0-22.0; p<0.001), and AP patients also showed significantly improved Chronic Liver Disease Questionnaire (CLDQ) scores compared with SoC patients (p<0.05 between treatment arms). Improvements in nutritional parameters were observed for hand-grip strength (p=0.044) and body mass index (p<0.001) in the sub-study. Compared with SoC, more AP patients reported adverse events (AEs; 96.3% vs. 77.4%, p=0.057) and serious AEs (85.2 vs. 45.2%, p=0.002). AEs consisted predominantly of acute kidney injury in the immediate post-operative period, and re-intervention for pump related issues, and were treatable in most cases. Survival was similar in AP and SoC. CONCLUSIONS: The AP system is effective for reducing the need for paracentesis and improving quality of life in cirrhotic patients with RA. Although the frequency of SAEs (and by inference hospitalizations) was significantly higher in the AP group, they were generally limited and did not impact survival. Lay summary: The alfapump® moves abdominal fluid into the bladder from where it is then removed by urination. Compared with standard treatment, the alfapump reduces the need for large volume paracentesis (manual fluid removal by needle) in patients with medically untreatable ascites. This can improve life quality for these patients. www.clinicaltrials.gov#NCT01528410.
Authors: Maria Stepanova; Fatema Nader; Christophe Bureau; Danielle Adebayo; Laure Elkrief; Dominique Valla; Markus Peck-Radosavljevic; Anne McCune; Victor Vargas; Macarena Simon-Talero; Juan Cordoba; Paolo Angeli; Silvia Rossi; Stewart MacDonald; Jeroen Capel; Rajiv Jalan; Zobair M Younossi Journal: Qual Life Res Date: 2018-02-19 Impact factor: 4.147
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Authors: Valerie Will; Susana G Rodrigues; Guido Stirnimann; Andrea De Gottardi; Jaime Bosch; Annalisa Berzigotti Journal: United European Gastroenterol J Date: 2020-06-26 Impact factor: 4.623
Authors: Amine Benmassaoud; Suzanne C Freeman; Davide Roccarina; Maria Corina Plaz Torres; Alex J Sutton; Nicola J Cooper; Laura Iogna Prat; Maxine Cowlin; Elisabeth Jane Milne; Neil Hawkins; Brian R Davidson; Chavdar S Pavlov; Douglas Thorburn; Emmanuel Tsochatzis; Kurinchi Selvan Gurusamy Journal: Cochrane Database Syst Rev Date: 2020-01-16
Authors: G Stirnimann; T Berg; L Spahr; S Zeuzem; S McPherson; F Lammert; F Storni; V Banz; J Babatz; V Vargas; A Geier; A Stallmach; C Engelmann; C Trepte; J Capel; A De Gottardi Journal: Aliment Pharmacol Ther Date: 2017-09-21 Impact factor: 8.171