Percutaneously Delivered Automated Continual Fluid Removal System in Patients With Advanced Diuretic-Resistant Heart Failure

A Multi-Center, Multinational, Prospective, Open-Label, Single Arm, Pilot Study to Assess the Feasibility, Safety and Tolerability of a Percutaneously Delivered Automated Continual Fluid Removal System in Patients With Advanced Diuretic-Resistant Heart Failure

The study aims to assess the feasibility, safety, tolerability and functionality of a percutaneously delivered automated continual fluid removal System in up to 8 patients with Heart Failure (HF) and diuretic resistance.

Intervention: Implanted absorption chamber, connected to an external pump. Follow up: 6 months post activation.

Objectives: To assess the feasibility, safety, tolerability and functionality of an intra-peritoneal, mechanically induced ultrafiltration system (IPUDx), through the analysis of procedure and device related serious adverse events and device function.

Study Duration: Up to 24 months. Enrolment 15 months, Activation following implantation (per patient) up to 1 month, Follow-up (per patient) 6 months, Close-out 2 months.

Number of Subjects: Up to 8 Diagnosis and Main Inclusion Criteria: Patients with fluid overloaded congested heart failure (The New York Heart Association Class II-IV) with diuretic resistance and a history of multiple heart failure related admissions.

Study Centers: Up to 5 Medical Centers in Serbia and Spain.

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 a daily disposable external fluid drainage bag.

Statistical Methodology: No statistical hypothesis is proposed. Safety will be evaluated using a complete description of Serious Adverse Events (SAEs). A descriptive analysis will be performed for all primary and secondary variables of the study for the basal measures and all post-basal measures. Interim analysis for all the study endpoints will be performed at the completion of the active follow up phase (3 months post activation). Safety analysis for Adverse Device Effects (ADEs) will be performed both at 3-month post activation and at the completion of maintenance phase (6 months post implantation).

Inclusion Criteria:

• ≥ 21 years of age
• Life expectancy > 6 months
• Heart Failure, New York Heart Association (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
• Able to give written informed consent
• Ability to comply with study procedures and ability to operate the device themselves or by a regular caregiver support
• Residence in proximity to the medical center to ensure easy access for required hospital visits and to enable home visits
• 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 a history, or with an indication for mechanical circulatory support

• intravenous (IV) inotropes required in last 3 months (INTERMACS Score

  • 3), excluding Levosimendan

• Immunocompromised (e.g. chronic steroid treatment, Human immunodeficiency virus (HIV), etc.)

• Insulin dependent diabetes with evidence of infection

• Severe hyponatremia as defined by a serum Sodium < 120 mmol/l

• Serum Albumin < 2.5 g/Dl

• Glomerular filtration rate (eGFR) < 20 ml/min/1.73m2 by MDRD method, using MDRD 4-variable equation that includes age, sex, ethnicity, and serum creatinine

• Previous significant intraabdominal surgery, severe abdominal adhesions, intra-abdominal foreign body (except for small inguinal mesh)

• Current or historical (within last 6 months) large diaphragmatic hernia, or surgically irreparable, complex or recurring hernia

• 6 minutes walk test of less than 100 meters in all repeated testing (if applicable), or similar test

• Severe, multiple repeated cardiac-related ascites, subject to principal investigator (PI) discretion

• Inflammatory or ischemic bowel disease (i.e., Crohn's disease, ulcerative colitis) and frequent episodes of diverticulitis

• Current gastrointestinal active infection in the body (such as Clostridium difficile infection)

• 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

• Class B or C liver cirrhosis of non-cardiac aetiology

• 18.5 > body mass index (BMI) > 40 presenting a risk for surgery

• Patients with contraindications for general/local anaesthesia, sedation and

  • or Percutaneous / Laparoscopic surgery

• Unsuitability for self-maintenance of the experimental home set-up

• Presence of any current cancer, subject to PI discretion

• Presence of any active implantable or body-worn devices that cannot be removed excluding Implantable Cardioverter-Defibrillator (ICD) / pacemaker, subject to PI discretion

• Known hypersensitivity to Nitinol nickel/titanium alloy and brilliant blue

• Pregnancy

• Patients being in another therapeutic clinical study