Alfapump® System in the Treatment of Refractory or Recurrent Ascites (POSEIDON Study)

Ascites Clinical Trial

— POSEIDON  

Official title:

Alfapump® System in the Treatment of Refractory or Recurrent Ascites: a Multicenter Single Arm Within Subject Crossover Design Pivotal Study (the POSEIDON Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03973866
• Other study ID #: 2017-AAR-010
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 16, 2019
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2022
• Source: Sequana Medical N.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The POSEIDON study is a multi-center, prospective, single arm, crossover pivotal study enrolling up to 70 pivotal cohort patients and up to 45 additional Roll-in patients with refractory or recurrent ascites at up to 20 sites. Pivotal cohort patients will undergo a 3-month pre-implant observation phase after enrollment, followed by implantation of the alfapump and 24 months of post-implant follow up. An analysis will be conducted to support an application for device approval when a minimum of 40 treated pivotal cohort patients are through 6 months.

Description:

The POSEIDON Study is a multicenter, single arm within subject crossover design pivotal trial conducted in patients diagnosed with refractory or recurrent ascites due to liver cirrhosis who meet inclusion/exclusion criteria. The study will enroll up to 70 pivotal cohort patients with refractory or recurrent ascites at up to 20 sites. In addition, up to 45 additional Roll-in patients will be allowed. An analysis will be conducted to support an application for device approval when a minimum of 40 treated pivotal cohort patients are through 6 months. Patients will be followed for longer-term safety and effectiveness for a total of 2-years post-implant. Patients with a functioning pump at 24 months may consent to continued participation in a long-term follow-up evaluation and with assessments every 3 months from 24 months through the time the pump ceases to function, pump explant or patient death. This long-term follow-up period will continue until the product is approved or the sponsor determines they will no longer pursue product approval.

Pivotal Cohort Patients

Pivotal cohort patients will be evaluated in a 3-month pre-implant observation period during which they will receive standard of care therapy consisting of paracentesis as required for removal of ascitic fluid. Following the initial 3-month observation period during which the number and volume of paracentesis and Quality of life (assessed by general HRQL scores (SF-36)) as well as disease-specific validated questionnaires (Ascites-Q) will be documented, patients will be reevaluated for eligibility for pump implant.

Roll-in Patients

In the study centers without previous experience in pump placement, training in the pump implant procedure will be conducted and up to 3 initial pump implantations conducted as roll-in cases. Roll-in patients will be sequentially enrolled at the site until sufficient experience has been obtained and the site is approved by the sponsor to enroll in the pivotal phase. Roll-in patients will not undergo the 3-month pre-implant observation period and will not be included in the Primary Analysis set but will be summarized separately for purposes of safety evaluation with effectiveness data provided as supplemental. In the event a primary implanter at the site is a replaced or added, up to 3 additional Roll-in implants will be allowed.

All patients (Pivotal and Roll-in) will undergo a final eligibility assessment prior to pump implant. If deemed eligible, patients will be implanted with the alfapump. In the 3 months post-implant, patients will be monitored with pump adjustments as needed to increase or decrease volume of fluid to be removed each day. After this period of stabilization, a 3-month primary endpoint observation period (month 4 through month 6) will begin. In each period, the protocol specifies when symptom driven (therapeutic) paracentesis can be performed per protocol as well as conditions under which the use of diuretics may be considered (all patients must discontinue diuretics post implant procedure).

The study is designed to demonstrate in pivotal cohort patients 1) a 50% reduction (superiority margin) in the per-patient ratio of post-implant 3-month observation period (M4 to M6 post implantation) to pre-implant 3-month observation period with respect to average monthly requirement for therapeutic paracentesis and 2) at least 50% of patients will achieve a 50% reduction in the requirement for therapeutic paracentesis in the same period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: June 30, 2024
• Est. primary completion date: March 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

At the time of Initial Screening:

1. Patients > 18 years of age

2. Cirrhosis of the liver defined by histological and/or clinical, endoscopic, laboratory and radiological criteria.

3. Refractory or recurrent ascites primarily managed with periodic therapeutic paracentesis . Patients must have a minimum of 2 therapeutic paracenteses in the 30 Days prior to enrollment

4. Not a candidate for (e.g. refused, contraindicated) Transjugular intrahepatic portosystemic shunt (TIPS) or previously implanted TIPS is permanently obstructed or non-functioning.

5. Screened for esophageal varices and on optimal management

6. Absence of contraindications to prophylactic antibiotic use from time of pump implant

7. Life expectancy of at least 6 months following pump implant (approximately 10 months from enrollment)

8. Capable of giving written informed consent, willing to comply with study procedures including the 3-month pre-implant observation period and ability to operate and charge the device.

9. Women of childbearing age should use adequate contraceptives.

Reassessed at time of implant procedure (Pivotal Cohort Only):

10. Has required a minimum of 5 therapeutic paracenteses in the 3-month observation period prior to pump implant

Exclusion Criteria:

At the time of Initial Screening:

1. Renal failure defined as serum creatinine higher than 1.5 mg/dL

2. More than one episode of spontaneous bacterial peritonitis over the previous 6 months

3. More than one episode of bacterascites over the previous 6 months

4. Recurrent urinary infections as per standard criteria, defined as 2 or more episodes over the last 6 months

5. Evidence of loculated ascites, as per imaging

6. Hepatocellular carcinoma, exceeding Milan criteria or for which RF ablation is anticipated

7. Pregnant females or females anticipating pregnancy during study period

8. Patients currently enrolled in another interventional clinical study that has not reached the primary endpoint assessment point, or (for pivotal cohort) patients who have previously had an alfapump implanted

9. Immuno-modulatory treatment (including azathioprine, methotrexate, anti-TNF therapies) used within last 4 months (corticosteroids at stable dose over the last 4 months but < 15 mg/day, or in tapering doses are allowed)

10. Known or suspected hepatic or extra hepatic malignancy (other than skin cancer and in-situ cancers), unless adequately treated or in complete remission for = 3 years

11. History of bladder cancer

12. BMI>40 presenting a risk for technical difficulties for surgery or catheter implantation

13. Contraindications to general anesthesia

14. Comorbid condition or other reason (example hypertension) that may preclude stopping diuretics after enrollment

15. MELD-Na Score > 20

16. Budd Chiari syndrome (Pivotal cohort only)

17. Clostridium difficile infection within the past year

Assessed or re-assessed at time of pump implant:

18. Acute gastrointestinal hemorrhage requiring transfusions over the previous 42 days

19. Condition that prevents continued cessation of diuretic use

20. Patient condition does not allow the implant procedure to be performed within the limits of acceptable risk (e.g. cardiovascular comorbidities, variceal bleeding within the previous 6 weeks, skin infections or skin ulcers of the anterior abdominal wall within 2 weeks of device placement)

21. Hepatocellular carcinoma exceeding Milan criteria or for which RF ablation is anticipated

22. ICU admission since enrollment in the 30 days preceding pump implant procedure

23. INR >/= 2.0

24. Platelet count of < 50,000 /µL at the time of implantation, unless the platelet count is =30,000 / µL and bleeding risk can be satisfactorily addressed with means such as platelet infusion during the implant procedure and/or thrombopoietin receptor agonists

25. Bacterial peritonitis within 4 weeks of implant procedure (this includes peritonitis diagnosed at the time of intervention)

26. Bacterascites within 4 weeks of implant procedure (this includes bacterascites diagnosed at the time of intervention). Note: at the time of final eligibility (just prior to implantation) the subject will not be allowed to move forward with the procedure if he/she has experienced an episode bacterascites within four weeks of the implant procedure date.

27. Serum sodium <125 mmol/L

28. Urinary infection within the last 2 weeks

29. Obstructive uropathy, residual urinary volume exceeding 100 ml, or any bladder anomaly which might contraindicate implantation of the device

30. Evidence of renal failure, defined as serum creatinine higher than or equal to 1.5 mg/dL, in the preceding 30 days

31. Evidence of loculated ascites, as per imaging

32. Pregnant females or females anticipating pregnancy during study period

Related Conditions & MeSH terms

• Ascites

Intervention

Device:
• Alfapump
Implantation of alfapump

Locations

Country	Name	City	State
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Baylor University Medical Center (Dallas)	Dallas	Texas
United States	Methodist Dallas	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Cedars-Sinai Comprehensive Transplant Center	Los Angeles	California
United States	Medical College of Wisconsin (Froedtert)	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic (Arizona)	Phoenix	Arizona
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Avera Medical Group	Sioux Falls	South Dakota
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sequana Medical N.V.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Per-patient ratio of post-implant to pre-implant with respect to average monthly number of therapeutic paracentesis	Defined as removal of ascites =1.5L through needle puncture of abdominal wall	Comparing data from the post-implant 3-month observation period to data from the pre-implant 3-month observation period:
Primary	Proportion of patients with at least 50% reduction in number of therapeutic paracenteses from the pre-observation period to post-observation period	Defined as removal of ascites =1.5L through needle puncture of abdominal wall	Comparing data from the post-implant 3-month observation period to data from the pre-implant 3-month observation period
Primary	Combined rate of open surgical reintervention due to pump system related adverse event or to restore pump functionality, pump explant due to pump system related adverse event, or pump system related death	Safety of the alfapump implant procedure and alfapump therapy as determined by rates of explant, reintervention, and other serious device or procedure related adverse events	from time of pump implant through 6 months post-implant
Secondary	Requirement for large volume paracentesis (LVP): change in the average number of LVP events per month (that consist of removing = 5L of ascitic fluid)	Effectiveness of the alfapump to control ascites as determined by the change in the need for repeated paracentesis compared to baseline	in the post-implant 3-month primary endpoint observation period compared to the pre-implant observation period
Secondary	Change of cumulative volume of ascitic fluid removed by means of therapeutic paracentesis	Effectiveness of the alfapump to control ascites as determined by the change in the need for repeated paracentesis compared to baseline	in the post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period
Secondary	Change in SF-36 Physical Component Score	The Medical Outcomes Study Short Form Survey Instrument (SF-36) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal/emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes one item that indicates a perceived change in health. Scoring the SF-36 is a two-step process. First, precoded numeric values are recoded per a scoring key. A high score defines a more favorable health state. Each item is scored on a 0-100 range. The lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Scale scores represent the average for all items in the scale that the respondent answered.	post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period
Secondary	Change in Ascites-Q Score	The Ascites-Q was developed by modifying the Polycystic Liver Disease Questionnaire. It includes 11 out of 16 original questions, covering symptoms of abdominal fullness, anorexia, early satiety, nausea, abdominal pain, back pain, dyspnea, reduced mobility, fatigue, insomnia, discomfort because of abdomen size, and problems with sexual intimacy. One other ascites-specific symptom (insomnia) was added. Each individual symptom is assessed with a frequency (6-point Likert scale "never" to "always") and discomfort (5-point Likert scale "not at all" to "a lot") question. Severity scores of individual symptoms are the sum of the frequency and discomfort score (range 2-11). A higher score represents a worse outcome.	in the post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period