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

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ClinicalTrials.gov Identifier: NCT03973866
Recruitment Status : Recruiting
First Posted : June 4, 2019
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Sequana Medical N.V.

Tracking Information
First Submitted Date  ICMJE May 31, 2019
First Posted Date  ICMJE June 4, 2019
Last Update Posted Date November 13, 2020
Actual Study Start Date  ICMJE September 16, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • Per-patient ratio of post-implant to pre-implant with respect to average monthly number of therapeutic paracentesis [ Time Frame: Comparing data from the post-implant 3-month observation period to data from the pre-implant 3-month observation period: ]
    Defined as removal of ascites ≥1.5L through needle puncture of abdominal wall
  • Proportion of patients with at least 50% reduction in number of therapeutic paracenteses from the pre-observation period to post-observation period [ Time Frame: Comparing data from the post-implant 3-month observation period to data from the pre-implant 3-month observation period ]
    Defined as removal of ascites ≥1.5L through needle puncture of abdominal wall
  • 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 [ Time Frame: from time of pump implant through 6 months post-implant ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
  • Requirement for large volume paracentesis (LVP): change in the average number of LVP events per month (that consist of removing ≥ 5L of ascitic fluid) [ Time Frame: in the post-implant 3-month primary endpoint observation period compared to the pre-implant observation period ]
    Effectiveness of the alfapump to control ascites as determined by the change in the need for repeated paracentesis compared to baseline
  • Change of cumulative volume of ascitic fluid removed by means of therapeutic paracentesis [ Time Frame: in the post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period ]
    Effectiveness of the alfapump to control ascites as determined by the change in the need for repeated paracentesis compared to baseline
  • Change in SF-36 Physical Component Score [ Time Frame: post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period ]
    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.
  • Change in Ascites-Q Score [ Time Frame: in the post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • Requirement for large volume paracentesis (LVP): reduction in the average number of LVP events per month (that consist of removing ≥ 5L of ascitic fluid) [ Time Frame: in the post-implant 3-month primary endpoint observation period compared to the pre-implant observation period ]
    Effectiveness of the alfapump to control ascites as determined by the reduction in the need for repeated paracentesis compared to baseline
  • Reduction of cumulative volume of ascitic fluid removed by means of therapeutic paracentesis [ Time Frame: in the post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period ]
    Effectiveness of the alfapump to control ascites as determined by the reduction in the need for repeated paracentesis compared to baseline
  • Improvement in SF-36 Physical Component Score [ Time Frame: post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period ]
    the SF-36 includes 36 questions that measure function health and well-being. Improvement is the component score would mean a higher score.
  • Improvement in Ascites-Q Score [ Time Frame: in the post-implant 3-month primary endpoint observation period as compared to the pre-implant 3-month observation period ]
    The Ascites-Q is a disease-specific validated symptom assessment questionnaire. Improvement in the Ascites-Q score would mean a lower score.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Alfapump® System in the Treatment of Refractory or Recurrent Ascites (POSEIDON Study)
Official Title  ICMJE Alfapump® System in the Treatment of Refractory or Recurrent Ascites: a Multicenter Single Arm Within Subject Crossover Design Pivotal Study (the POSEIDON Study)
Brief Summary The POSEIDON study is a multi-center, prospective, single arm, crossover pivotal study enrolling up to 60 pivotal cohort patients and up to 40 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.
Detailed 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 60 pivotal cohort patients with refractory or recurrent ascites at up to 20 sites. In addition, up to 40 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 6 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ascites
Intervention  ICMJE Device: Alfapump
Implantation of alfapump
Study Arms  ICMJE Experimental: Alfapump
Implantation of Alfapump
Intervention: Device: Alfapump
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 13, 2020)
100
Original Estimated Enrollment  ICMJE
 (submitted: May 31, 2019)
90
Estimated Study Completion Date  ICMJE March 1, 2024
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Recurrent urinary infections as per standard criteria, defined as 2 or more episodes over the last 6 months
  4. Evidence of loculated ascites, as per imaging
  5. Hepatocellular carcinoma, exceeding Milan criteria or for which RF ablation is anticipated
  6. Pregnant females or females anticipating pregnancy during study period
  7. 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
  8. 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)
  9. 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
  10. History of bladder cancer
  11. BMI>40 presenting a risk for technical difficulties for surgery or catheter implantation
  12. Contraindications to general anesthesia
  13. Comorbid condition or other reason (example hypertension) that may preclude stopping diuretics after enrollment
  14. MELD-Na Score > 20
  15. Budd Chiari syndrome (Pivotal cohort only)
  16. Clostridium difficile infection within the past year

    Assessed or re-assessed at time of pump implant:

  17. Acute gastrointestinal hemorrhage requiring transfusions over the previous 42 days
  18. Condition that prevents continued cessation of diuretic use
  19. 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)
  20. Hepatocellular carcinoma exceeding Milan criteria or for which RF ablation is anticipated
  21. ICU admission since enrollment in the 30 days preceding pump implant procedure
  22. Coagulopathy defined as INR > 2.0
  23. 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
  24. Bacterial peritonitis within 4 weeks of implant procedure (this includes peritonitis diagnosed at the time of intervention)
  25. Serum sodium <125 mmol/L
  26. Urinary infection within the last 2 weeks
  27. Obstructive uropathy, residual urinary volume exceeding 100 ml, or any bladder anomaly which might contraindicate implantation of the device
  28. Evidence of renal failure, defined as serum creatinine higher than or equal to 1.5 mg/dL, in the preceding 30 days
  29. Evidence of loculated ascites, as per imaging
  30. Pregnant females or females anticipating pregnancy during study period
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeroen Capel, MSc +41-44-4035512 jeroen.capel@sequanamedicl.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03973866
Other Study ID Numbers  ICMJE 2017-AAR-010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sequana Medical N.V.
Study Sponsor  ICMJE Sequana Medical N.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Florence Wong, MD Toronto General Hospital
PRS Account Sequana Medical N.V.
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP