An Automated Continual Water Removal System in Patients With Advanced Diuretic Resistant Heart Failure

Study Overview
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Brief Summary
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This study will assess the functionality and tolerability of an automated continual water removal system in up to 8 patients with HF and diuretic resistance. intervention: Implanted absorption chamber, connected to an external pump. Follow up: 3 months post activation.

Detailed Description
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Study Duration: 24 months Enrolment 20 months, Follow-up 3 months, Close-out 1 month Study Centres Up to 4 centres with Medical University Wroclaw, Poland, as the principal site. Objectives: To assess the feasibility, tolerability and functionality of an intra-peritoneal, mechanically induced, ultrafiltration system, through the analysis of procedure and device related serious adverse events and device function. Number of Subjects: Up to 8 Diagnosis and Main Inclusion Criteria: Patients with fluid overloaded congested heart failure (NYHA Class II-IV) with diuretic resistance and a history of multiple heart failure related admissions. Study Product and Planned Use: The Paragate Medical IPUDx System comprises an intraperitoneally implanted fluid absorption chamber with an external wearable rechargeable pump, drainage bag and controller. The system induces isotonic fluid loss across the peritoneal membranes which is collected in the fluid absorption chamber and transported to the external fluid drainage bag. Statistical Methodology: No statistical hypothesis is proposed. Safety will be evaluated using a complete description of Serious Adverse Events. A descriptive analysis will be performed for all primary and secondary variables of the study for the basal measures and all post-basal measures.

Official Title
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A Multi-centre, Prospective, Open Label, Uncontrolled Pilot Study to Assess the Feasibility and Tolerability of an Automated Continual Water Removal System in Patients With Advanced Diuretic Resistant Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Device: automated continual water removal system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 21 years of age Life expectancy > 6 months HF, NYHA class II-IV > 1 HF related admissions in the last 12 months Fluid congestion (2 signs of pitting oedema, jugular distention, BW elevation, nocturnal dyspnoea score, respiration rate, pulmonary congestion and/or pleural effusion per chest x-ray, ascites) Failure to achieve effective diuresis and congestion relief despite appropriate or escalating diuretic doses or combination of diuretics (eg. Furosemide and Metolazone) Eligible for general anaesthesia and laparoscopic procedure Able to give written informed consent Ability to comply with study procedures and ability to operate the device Women of childbearing potential should use adequate contraception for as long as the device is implanted. Exclusion Criteria: • Any non-cardiac disease with life expectancy < 1 year Any patient listed for solid organ transplantation Patients with history, or with indication for, mechanical circulatory support iv inotropes required in last 3 months (INTERMACS Score ≤3) Immunocompromised (e.g. chronic steroid treatment, HIV, etc.) Insulin dependent diabetes Severe hyponatraemia as defined by a serum Sodium < 120 mmol/l Serum Albumin < 2.5 g/dL eGFR < 25 ml/min/1.73m2 by MDRD method Previous significant intraabdominal surgery, severe abdominal adhesions, intra-abdominal foreign body (except for small inguinal mesh) Large diaphragmatic hernia, or surgically irreparable, complex or recurring hernia 6 minutes' walk test of less than 100 meter History (>6 months) of diaphragmatic hernia, inflammatory or ischemic bowel disease and frequent episodes of diverticulitis Gastrointestinal haemorrhage within the last 4 months Bacterial peritonitis episode within the last 24 months > 2 systemic or local infections, such as urinary tract infection or abdominal skin infection within the last 6 months Liver cirrhosis BMI > 40 presenting a risk for surgery Patients with contraindications for general anaesthesia or laparoscopic surgery Unsuitability for self-maintenance of the experimental home set-up Presence of any current cancer Presence of any active implantable or body-worn devices that cannot be removed excluding ICD / pacemaker Pregnancy Patients being in another therapeutic clinical study

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Implanted device<br>Implantation and activation of an automated continual water removal system, including 4-months follow up | Device: automated continual water removal system<br>* The device removes excess fluids in heart failure patients with diuretic resistance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of AEs related to implantation | Analysis of incidence and severity of AEs that occur during or following implantation and are related to it. | 4 months | 
| Analysis of AEs related to the device and its function. | Analysis of incidence and severity of AEs related to the device and its function. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functionality | Assessed by a daily volume of fluid removal | 4 months | 
| Clinical assessment of fluid overload | Fluid retention measures such as pitting oedema, jugular distention, body weight elevation | 4 months | 
| Echocardiographic assessment of LVESD, LVEDD, and LVEF | Data from echocardiography will enable the provision of volumes, diastolic function, right ventricular function, hemodynamics, and valvular regurgitation. This versatile tool is employed vastly for the management of heart failure. LVEF - Left Ventricular Ejection Fraction LVESD -Left Ventricular End-Systolic Diameters LVEDD - Left Ventricular external end-diastolic diameter | 4 months | 
| Quality of life questionnaire | KCCQ-12 questionnaire The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life (QOL) within a 2-week recall period. KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. | 4 months | 
| Nocturnal dyspnea score | Will be assessed using the following questions: Has the patient ever woken up at night with shortness of breath? How long after lying down did the episode occur? Number of pillows used under the patient's head at night: Has the patient ever had to sleep sitting up? Has the patient developed coughing or wheezing in the recumbent position? What did the patient do to relieve his distress? Please specify. | 4 months | 
| 6 minutes' walk test | The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. | 4 months | 
| NT-proBNP | NT-proBNP is a marker for HF severity. | 4 months | 
| Serum Creatinine | A marker for kidney function. | 4 months | 
| Serum / urine electrolytes levels. | Electrolyte and metabolite disorders indicate on kidney function. hypercalcemia /hypocalcemia. hyperchloremia /hypochloremia. hypermagnesemia /hypomagnesemia. hyperphosphatemia /hypophosphatemia. hyperkalemia /hypokalemia. hypernatremia /hyponatremia. | 4 months |