Malignant Ascites Alfapump® Study (ProMAS)

Prospective Study in the Use of the Alfapump® in the Treatment of Malignant Ascites

ProMAS is a prospective post-marketing, single-arm study to assess performance and safety of the Alfapump® system in the treatment of patients with malignant ascites. The study aims to enroll 40 patients in up to 8 sites in Europe.

Study Overview

• Status: Withdrawn
• Conditions: Malignant Ascites
• Intervention / Treatment: Device: alfapump system

Detailed Description

The Prospective Malignant Ascites Alfapump® study is a single-arm, prospective study to evaluate the performance and safety of the Alfapump® system in the treatment of patients with malignant ascites. The Alfapump® system is a fully implantable programmable pump, able to move ascitic fluid from the peritoneal cavity to the bladder via 2 catheters. The Alfapump® has obtained CE (Conformité Européenne) mark approval for the indication of malignant ascites. The primary objective of the study is to assess the performance of the system to remove ascites. Secondary objectives are to evaluate the safety and tolerability of the Alfapump® in the treatment of malignant ascites for a total follow-up period of 9 months, and to evaluate quality of life (QoL) by reduction or elimination of paracentesis requirement. Furthermore the study includes an exploratory scientific objective as to feasibility to obtain 'liquid biopsy' samples suitable for analysis in a non-invasive way after Alfapump® implantation. 40 patients with malignant ascites will be enrolled in up to 8 sites in Europe (Belgium, United Kingdom, Switzerland). Specific sub-analysis of data from patients with gynecological (ovarian) cancer is planned.

• Study Type: Observational

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W120HS
    • Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Investigators will be asked to enrol subjects meeting the inclusion and exclusion criteria .This study population is highly palliating with overall limited prognosis and significant comorbidities and possibly reduced performance status. Subjects must be under the care of an oncologist specialised in their disease. In the case of hepatic involvement, a hepatologist, and in the case of ovarian or breast cancer a gynaecologic oncologist accustomed to managing subjects with advanced malignancy. Subjects will be enrolled into the trial from the clinical practices of the investigators. Suitable subjects will undergo screening, including detailed medical history, paracentesis history and blood tests, to ensure compliance with study inclusion / exclusion criteria.

Description

Inclusion Criteria:

1. Subject is ≥ 18 years of age;
2. Subject has provided written informed consent; 3.Subject has recurrent malignant ascites defined as ≥2 therapeutic paracenteses in the month prior to enrolment; 4.Subject has sufficient baseline data documented for at least 4 paracentesis events in the last 3 months pre-implant, including date and volume; 5.Subject has ascites following neoplastic disease, as assessed by physician. In subjects with primary malignancy of the liver it should be confirmed that the ascites is due to malignancy and not due to underlying pre-existing cirrhosis.

6.Subject has a life expectancy of ≥3 months as assessed by the treating physician, and is receiving or intended to receive anticancer therapy.

7.Subject has the ability to comply with study procedures, including all follow-up visits at implanting centre when required, and ability to perform subject-required system tasks (charging). A subject with a caregiver who can comply with the study procedures and to perform the tasks required for appropriate pump function is allowed as well.

Exclusion Criteria:

1. Subject has evidence of multiple ascites loculation
2. Ascites analysis with neutrophil count >250/µl within 24-hours prior to implant.
3. Subject has acute Urinary Tract Infection (UTI) within 24-hours of implantation assessed by urinalysis.
4. Subject has skin infection of the abdominal wall at the area of implantation.
5. Subject has a serum creatinine > 1.5 mg/dL Subject has
6. Subject has obstructive uropathy (bladder residual volume >100 mL, determined by catheterization or abdominal ultrasound) in case of Lower Urinary Tract Symptoms (LUTS) .
7. Existing bladder anomaly denying proper catheterization of the bladder.
8. Subject has active bleeding or thrombocytopenia < 45,000 X106/L.
9. Subject on long-term prophylactic anticoagulation
10. Subject is pregnant or a female of childbearing potential.
11. Patient has recurrent requirement for MRI
12. Subject is currently participating in an oncology trial which might be negatively affected by the alfapump as assessed by the treating physician

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monthly therapeutic paracentesis frequency up to 3 months	Monthly therapeutic paracentesis frequency up to 3 months compared to the baseline therapeutic paracentesis frequency. The monthly therapeutic paracentesis frequency up to 3 months is defined as the average rate of therapeutic paracenteses during month 1, 2 and 3 post-implantation. Baseline therapeutic paracentesis frequency is defined as the average rate of therapeutic paracentesis in the 3 months prior to pump implantation.	3 months post-implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monthly therapeutic paracentesis frequency up to 6 months	Monthly therapeutic paracentesis frequency up to 6 months compared to the baseline therapeutic paracentesis frequency. The monthly therapeutic paracentesis frequency at 6 months is defined as the average rate of therapeutic paracenteses during months 1 to 6 Baseline therapeutic paracentesis frequency is defined as the average rate of therapeutic paracentesis in the 3 months prior to pump implantation.	6 months post-implantation
Safety outcome: free survival	Therapeutic paracentesis free survival after Alfapump® implantation	Time (days) to first paracentesis after implantation through 270 days post implantation
Efficacy outcome- Assessment of changes in Quality of Life	Changes in Quality of life after Alfapump® implantation, measured with validated EORTC cancer related Quality of life Questionnaire-CR29 (ColoRectal 29 questions) in subjects with colorectal malignancy.	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Efficacy outcome- Assessment of changes in Quality of Life	Changes in Quality of life after Alfapump® implantation assessed with validated FACIT-AI 5Ascites Index) ascites related quality of life questionnaire in all subjects enrolled in the study.	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Efficacy outcome- Assessment of changes in Quality of Life	Changes in Quality of life after Alfapump® implantation, measured with validated EORTC-cancer related Quality of life questionnaire-OV28 (OVarian 28 questions), in subjects with a gynaecological malignancy.	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Nutritional status outcome	Change in nutritional status assessed by Psoas muscle measurement	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Nutritional status outcome	Change in nutritional status assessed by changes in serum Zinc	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Nutritional status outcome	Change in nutritional status assessed by changes in serum pre-albumin	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Nutritional status outcome	Change in nutritional status assessed by changes in serum phosphate	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Nutritional status outcome	Change in nutritional status assessed by changes in serum potassium	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Nutritional status outcome	Change in nutritional status assessed by changes in serum albumin	at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline
Pump performance	Total Monthly volume of ascitic fluid removed (sum of volumes removed during each month via either Alfapump® and via therapeutic paracentesis)	at 1-month, 3-month, 6-month and 9-month follow-up
Pump performance outcome - pump survival	Pump survival through study completion, up to 270 days post-pump implantation	Time (days) from implantation until explantation due to technical causes through study completion up to 270 days post-pump implantation
Pump performance outcome - pump survival	Pump survival through study completion, up to 270 days post-implantation	Time (days) from implantation until first exchange due to technical causes through study completion up to 270 days post-pump implantation
Pump performance outcome	Frequency of hospitalisations following Alfapump® implantation through study completion up to 270 days post-pump implantation	through study completion up to 270 days post-pump implantation
Pump performance outcome	Duration of hospitalisations following Alfapump® implantation through study completion up to 270 days post-pump implantation	throug study completion up to to 270 days post-pump implantation
Safety outcome - subject survival	Subject overall survival after Alfapump® implantation through study completion up to 270 days post-pump implantation	Time (days) until exitus through study completion up to 270 days post-pump implantation
Safety outcome- Bladder metastasis: Freedom from metastatic bladder wall infiltration	Freedom from metastatic bladder wall infiltration as assessed by cystoscopy	at 6-month follow-up
Safety outcome- Worsening of renal function	Incidence of subjects suffering Renal function deterioration, defined as a rise in serum creatinine of ≥50% or ≥0.3mg/dl .	at 3-month, 6-month and 9-month follow-up compared to baseline
Safety outcome- Incidence of device related infection	Incidence of Device-related infections following pump-implantation	at 3-month, 6-month and 9-month follow-up
Safety outcome- Incidence of Procedure related events	Incidence of Procedure related adverse events	At 1 month follow-up.
Safety outcome- Incidence of Device related events	Incidence of any Device-related adverse events	at 3-month, 6-month and 9-month follow-up
Device failure	Incidence of device failure resulting in re-intervention (Revision, exchange or explantation) through study completion up to 270 days post-pump implantation	Through study completion up to 270 days post-pump implantation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome- liquid biopsies	Incidence of successful acquisition of ascitic fluid samples appropriate for oncological analysis via Alfapump® function	2-days, 7-days, 3-months, 6-months and 9-months post implant
Exploratory outcome - anticancer treatment	Incidence of Initiation of new / change to existing anticancer treatment through study completion up to 270 days post-pump implantation	Time (days) to event through study completion up to 270 days post-pump implantation

Collaborators and Investigators

• Sponsor: Sequana Medical N.V.
• Investigators: Principal Investigator: Christina Fotopoulou, Prof, MD, Imperial Hospital, London, UK

Publications and helpful links

General Publications

• European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417. doi: 10.1016/j.jhep.2010.05.004. Epub 2010 Jun 1. No abstract available.
• Gines A, Fernandez-Esparrach G, Monescillo A, Vila C, Domenech E, Abecasis R, Angeli P, Ruiz-Del-Arbol L, Planas R, Sola R, Gines P, Terg R, Inglada L, Vaque P, Salerno F, Vargas V, Clemente G, Quer JC, Jimenez W, Arroyo V, Rodes J. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology. 1996 Oct;111(4):1002-10. doi: 10.1016/s0016-5085(96)70068-9.
• Gines P, Tito L, Arroyo V, Planas R, Panes J, Viver J, Torres M, Humbert P, Rimola A, Llach J, et al. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology. 1988 Jun;94(6):1493-502. doi: 10.1016/0016-5085(88)90691-9.
• Stirnimann G, Berg T, Spahr L, Zeuzem S, McPherson S, Lammert F, Storni F, Banz V, Babatz J, Vargas V, Geier A, Stallmach A, Engelmann C, Trepte C, Capel J, De Gottardi A. Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis. Aliment Pharmacol Ther. 2017 Nov;46(10):981-991. doi: 10.1111/apt.14331. Epub 2017 Sep 21.
• Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease. Aliment Pharmacol Ther. 2005 Mar 1;21(5):525-9. doi: 10.1111/j.1365-2036.2005.02387.x.
• Lin CH, Shih FY, Ma MH, Chiang WC, Yang CW, Ko PC. Should bleeding tendency deter abdominal paracentesis? Dig Liver Dis. 2005 Dec;37(12):946-51. doi: 10.1016/j.dld.2005.07.009. Epub 2005 Sep 26.
• Sola R, Vila MC, Andreu M, Oliver MI, Coll S, Gana J, Ledesma S, Gines P, Jimenez W, Arroyo V. Total paracentesis with dextran 40 vs diuretics in the treatment of ascites in cirrhosis: a randomized controlled study. J Hepatol. 1994 Feb;20(2):282-8. doi: 10.1016/s0168-8278(05)80070-4.
• MEDDEV 2.12-1, rev 7, Guidelines on a medical device vigilance system.
• Bureau C, Adebayo D, de Rieu MC, Elkrief L, Valla D, Peck-Radosavljevic M, McCune A, Abbadi R, Vargas V, Simon-Talero M, Cordoba J, Angeli P, Rosi S, MacDonald S, Malago M, Stepanova M, Younossi ZM, Trepte C, Watson R, Borisenko O, Sun S, Inhaber N, Jalan R. Corrigendum to "Alfapump(R) system vs. large volume paracentesis for refractory ascites: A multicenter randomized controlled study" [J Hepatol 67 (2017) 940-949]. J Hepatol. 2018 Mar;68(3):630. doi: 10.1016/j.jhep.2017.12.017. Epub 2018 Feb 1. No abstract available.
• Lai JC, Covinsky KE, Dodge JL, Boscardin WJ, Segev DL, Roberts JP, Feng S. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology. 2017 Aug;66(2):564-574. doi: 10.1002/hep.29219. Epub 2017 Jun 28.
• Chang L, Ni J, Zhu Y, Pang B, Graham P, Zhang H, Li Y. Liquid biopsy in ovarian cancer: recent advances in circulating extracellular vesicle detection for early diagnosis and monitoring progression. Theranostics. 2019 May 31;9(14):4130-4140. doi: 10.7150/thno.34692. eCollection 2019.
• Palmirotta R, Lovero D, Cafforio P, Felici C, Mannavola F, Pelle E, Quaresmini D, Tucci M, Silvestris F. Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology. Ther Adv Med Oncol. 2018 Aug 29;10:1758835918794630. doi: 10.1177/1758835918794630. eCollection 2018.
• Giannopoulou L, Kasimir-Bauer S, Lianidou ES. Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA. Clin Chem Lab Med. 2018 Jan 26;56(2):186-197. doi: 10.1515/cclm-2017-0019.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 31, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: OVARIAN; COLORECTAL; PARACENTESIS
• Additional Relevant MeSH Terms: Pathologic Processes; Ascites
• Other Study ID Numbers: 2018-AAR-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No individual participant data will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No