First-in-human Study to Examine Safety of a New Peritoneal Dialysis Device (WEAKID) in End-stage Kidney Disease Patients (CORDIAL)

Clinical Validation of a Continuous Flow Peritoneal Dialysis System With Dialysate Regeneration

The goal of this first-in-human clinical trial is to examine the safety and efficacy of treatment with a new peritoneal dialysis (PD) device called WEAKID (WEarable Artificial KIDney for peritoneal dialysis). This device, unlike conventional PD, allows for continuous flow of dialysate inside the abdominal cavity combined with continuous regeneration of spent dialysate thanks to sorbents that remove toxins from the fluid.

The study will include PD patients of 18 years or older with a well-functioning peritoneal catheter and no history of a PD-related infection for at least eight weeks prior to enrolment.

The main purpose of this study is to assess the (short-term) safety of the WEAKID system in a limited number (n=12) of patients and sessions.

Participants will undergo six treatment sessions (of four or eight hours) in total over a period of two weeks, either with or without a sorbent chamber.

Participants will be asked to collect urine and dialysate the week before the first treatment and during the treatment days. In addition, blood samples will be collected before and during the treatment weeks in order to compare the effects of conventional PD with that of WEAKID treatment. A peritoneal equilibrium test will also be done before and after the treatment weeks to test the function of the lining of the abdomen (the peritoneal membrane).

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Intervention / Treatment: Device: WEAKID

Detailed Description

Peritoneal dialysis (PD) is a life-sustaining renal replacement therapy for patients with end-stage kidney disease (ESKD). With PD, waste solutes and excess water are drawn from the blood across the peritoneal membrane lining the abdominal cavity via diffusion and osmosis, respectively, into dialysis fluid (peritoneal dialysate) that is introduced into the abdominal cavity through a permanent tube (peritoneal catheter). The peritoneal dialysate is replaced 4-6 times/day either manually by the patient or automatically by a machine at night while the patient is asleep. PD is a gentle dialysis technique that provides continuous gradual dialysis while the patient is free to move during the day. However, PD has several disadvantages. Removal of waste solutes is inadequate and technique failure rate is high, contributing to poor quality of life and high (co)morbidity and mortality (10-15% per year). The low solute clearance (~1-7% of that of healthy kidneys (depending on the solute) and lower than that with haemodialysis (HD)) is due to rapid decrease of diffusive transport of solutes during a dwell due to the disappearance of the plasma-to-dialysate concentration gradient across the peritoneal membrane. The limited technique survival (median 3.7 years) is primarily due to the high incidence of recurrent infection of the peritoneal membrane (peritonitis) and exposure of the peritoneal membrane to very high, harmful glucose concentrations needed for osmotic fluid removal.

Both peritonitis and high glucose concentrations cause pathological changes of the peritoneal membrane and eventually ultrafiltration failure necessitating a switch to the more invasive and expensive HD treatment. To reduce the existing shortcomings of conventional PD, a novel continuous flow peritoneal dialysis system with dialysate regeneration (WEAKID) for PD was developed. WEAKID treatment is based on continuous recirculation of peritoneal dialysate via the single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbent technology. The WEAKID nighttime system (weight: ~12 kg) is intended to be used for 8h per day (during the night) on a daily basis. Instead of performing 4-6 exchanges with fresh peritoneal dialysate per day, WEAKID uses one peritoneal dialysate filling which is continuously recirculated and regenerated. The continuous regeneration prevents saturation of the dialysate with toxins and thereby maintains a high plasma to dialysate concentration gradient which enhances diffusive transport of uremic toxins. In addition, the continuous recirculating flow of fluid along the peritoneal membrane is expected to increase the mass transfer area coefficient as observed in previous studies with continuous flow peritoneal dialysis, probably due to reduction of diffusion resistance, renewal of stagnant fluid layers at the tissue surface and an increase of the effective membrane area. Both the high plasma to dialysate concentration gradient and the increase in mass transfer contribute to an enhancement of the clearance. Another advantage of the WEAKID system is that the glucose peak load to peritoneum is lower than with traditional automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) thanks to the buffering of the sorbents (sorbents adsorb glucose at the start, lowering the initial glucose peak, and release the glucose again at later stage) and the continuous recirculation.

The primary objective of this study is to assess the (short-term) safety of the WEAKID nighttime system in a limited number (n=12) of patients and sessions (6 sessions per patient).

Secondary objectives of this study are:

1. To evaluate the incidence of adverse events (AEs) and device deficiencies (DDs) other than serious adverse device effects (SADEs) and DDs that could have led to a serious adverse event (SAE)
2. To describe the characteristics of WEAKID treatment (i.e. number and duration of sessions, dialysate flow rates)
3. To evaluate the clinical condition and vital signs of the participants during WEAKID treatment
4. To evaluate the effectiveness of ultrafiltration (UF) in relation to glucose concentration during WEAKID treatment
5. To evaluate the efficacy of solute removal and base release of WEAKID treatment
6. To evaluate the evolution of plasma analytes during WEAKID treatment
7. To evaluate the evolution of dialysate effluent analytes of the WEAKID system
8. To evaluate the (technical) device performance of the WEAKID system by the number of device deficiencies, adverse device effects and changes in intraperitoneal pressure
9. To evaluate patient tolerance during WEAKID treatment
10. To evaluate the evolution of uremic symptoms during WEAKID treatment
11. To evaluate the effectiveness of using sorbents for dialysate regeneration and the effectiveness of continuous recirculating flow in relation to the efficacy of solute removal.

The WEAKID system will be tested in a clinical setting on 6 days over a period of 2 weeks. During the first week, the subjects will be treated with the nighttime system without sorbents for 4h (first day) or 8h (second and third day) during daytime. The second week, treatment will consist of the nighttime system with sorbents (also 4h (first day) or 8h (second and third day) during daytime).

This way, exposure to new components of the system is incremental and the effectiveness of the sorbents can be analyzed separately from the effect of continuous recirculating flow dialysis. A peritoneal equilibration test (PET) will be performed at baseline and follow-up. In addition, patients will collect 24h spent peritoneal dialysate and 24h urine followed by venous puncture for blood sampling 3 times prior to WEAKID treatment during standard PD.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karin GF Gerritsen, MD. PhD; Phone Number: +31887557375; Email: k.g.f.gerritsen@umcutrecht.nl
• Study Contact Backup: Name: Dian P Bolhuis, MSc; Phone Number: +31887557375; Email: d.p.bolhuis-3@umcutrecht.nl

Study Locations

• Italy
  • Modena, Italy, 41121
    • Not yet recruiting
    • Università degli Studi di Modena e Reggio Emilia (UNIMORE)
    • Contact: Gabriele Donati, Prof., MD, PhD; Phone Number: +39-0594225331; Email: gabriele.donati@unimore.it
    • Contact: Giulia Ligabue, MSc, PhD; Phone Number: +39-0594224175; Email: giulia.ligabue@unimore.it
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • University Medical Center Utrecht (UMCU)
    • Contact: Karin GF Gerritsen, MD, PhD; Phone Number: +31-887557375; Email: k.g.f.gerritsen@umcutrecht.nl
    • Contact: Dian P Bolhuis, MSc; Phone Number: +31-887557375; Email: d.p.bolhuis-3@umcutrecht.nl
• Spain
  • Madrid, Spain, 28029
    • Not yet recruiting
    • Hospital Universario La Paz (SERMAS)
    • Contact: Gloria del Peso Gilsanz, MD, PhD; Phone Number: +34-913585339; Email: gloria.delpeso@salud.madrid.org
    • Contact: Maria A Bajo Rubio, MD, PhD; Phone Number: +34-913585339; Email: mauxiliadora.bajo@salud.madrid.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years of age
• Treated with PD for at least 3 months prior to enrolment
• Well-functioning peritoneal catheter and no peritoneal catheter replacement for at least a month prior to enrolment
• No PD-related infection (exit-site infection, tunnel infection or peritonitis) less than 8 weeks prior to enrolment (counting from the day that the treatment has been finished).
• Previous or current use of Extraneal® with no contra-indications
• Capable of understanding the patient information sheet and informed consent form (ICF) and give informed consent
• Willing and able to comply with all study procedures and attend all study visits

Exclusion Criteria:

• Patients who are unable to provide informed consent
• Patients who are unable to comply with study procedures
• Patients who received renal replacement therapy other than conventional PD less than 8 weeks prior to enrolment
• Patients who participated in an intervention trial less than 8 weeks prior to enrolment or are currently participating in an intervention trial. Patients in an observational study without any interventions or in post-market surveillance do not need to be excluded.
• Patients with a PD-related infection (exit-site infection, tunnel infection or peritonitis) less than 8 weeks prior to enrolment (counting from the day that the treatment has been finished)
• Patients with peritoneal catheter dysfunction or mechanical issues less than one month prior to enrolment
• Patients who have never used Extraneal® dialysis fluid or have a contra-indication for Extraneal®: a known allergy to cornstarch or icodextrin; maltose or isomaltose intolerance; glycogen storage disease
• Patients with an incompatible PD connection to the device (e.g. Fresenius PD system)
• Patients with haemoglobin concentrations < 6.2 mmol/L (< 10 g/dL) less than 8 weeks prior to enrolment
• Patients with hyperkalemia (> 6.0 mmol/L) or hyponatremia (< 130 mmol/L) in the 8 weeks prior to enrolment
• Patients with hypocalcemia (plasma total calcium concentration corrected for albumin <2.20 mmol/L or ionized calcium <1.15 mmol/L) or hypomagnesemia (plasma magnesium concentration <0.70 mmol/L) in the 8 weeks prior to enrolment
• Patients with any serious medical condition which in the opinion of the investigator, may adversely affect the safety of the participant and/or effectiveness of the study
• Female patients who are either (planning to become) pregnant within the study period or breast feeding
• Patients with a life expectancy <3 months
• Anticipated living donor kidney transplantation <3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WEAKID; Six treatments over the course of two weeks with the WEAKID system	Device: WEAKID; Six treatments over the course of two weeks with the WEAKID system: Week 1 (without the sorbents)Day 1: four-hour treatmentDay 2: eight-hour treatmentDay 3: eight-hour treatment; Week 2 (with the sorbents)Day 1: four-hour treatmentDay 2: eight-hour treatmentDay 3: eight-hour treatment; Other Names: CORDIAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse device effects (SADEs) and device deficiencies (DDs)	Serious adverse device effects (SADEs) and device deficiencies (DDs) that could have led to a serious adverse event	This will be assessed through study completion (four weeks in total per participant)
Critical changes in blood pressure	Critical changes requiring intervention in blood pressure (measured in mmHg; both systolic and diastolic pressures will be assessed).	This will be assessed during WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in heart rate	Critical changes requiring intervention in heart rate (measured in beats per minute).	This will be assessed during WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in body temperature	Critical changes requiring intervention in body temperature (measured in °C).	This will be assessed during WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in oxygen saturation	Critical changes requiring intervention in oxygen saturation (measured in %).	This will be assessed during WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in plasma potassium	Critical changes requiring intervention in plasma potassium (before and after WEAKID treatment in mmol/L).	This will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in plasma calcium	Critical changes requiring intervention in plasma calcium (before and after WEAKID treatment in mmol/L).	This will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in plasma bicarbonate	Critical changes requiring intervention in plasma bicarbonate (before and after WEAKID treatment in mmol/L).	This will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in intra-abdominal dialysate volume	Critical changes requiring intervention in intra-abdominal dialysate volume.	This will be assessed during WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Critical changes in intra-abdominal pressure	Critical changes requiring intervention in intra-abdominal dialysate pressure (in mbar).	This will be assessed during WEAKID treatment throughout the study treatment period (2 weeks in total per participant)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs) and device deficiencies (DDs)	Assessing incidence of adverse events (AEs) and device deficiencies (DDs) other than SADEs and DDs that could have led to an serious adverse event (SAE).	This will be assessed through study completion (four weeks in total per participant)
Number of WEAKID treatments	The number of WEAKID treatments per patient will be determined	The number of WEAKID treatments will be assessed for the study treatment period (2 weeks in total per participant)
Duration of WEAKID treatments	Duration of each WEAKID treatment will be assessed (in minutes).	This will be assessed for each WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Dialysate flow rates during WEAKID treatment	Dialysate flow rates will be determined during each WEAKID treatment (in mL/min).	This will be assessed during WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of blood pressure	Blood pressure will be measured multiple times during a WEAKID treatment to examine its evolution during treatment (in mmHg).	This will be assessed during WEAKID treatment at t=0 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of heart rate	Heart rate will be measured multiple times during a WEAKID treatment to examine its evolution during treatment (in beats per minute).	This will be assessed during WEAKID treatment at t=0 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of body temperature	Body temperature will be measured multiple times during a WEAKID treatment to examine its evolution during treatment (in °C).	This will be assessed during WEAKID treatment at t=0 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of oxygen saturation	Oxygen saturation will be measured multiple times during a WEAKID treatment to examine its evolution during treatment (in %).	This will be assessed during WEAKID treatment at t=0 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Ultrafiltration volume	For each WEAKID session, ultrafiltration volume will be determined (in mL).	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Peak glucose concentration in the device effluent	For each WEAKID session, peak glucose concentration in the effluent of the device will be determined (in mmol/L).	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Ultrafiltration efficiency	For each session, ultrafiltration efficiency (volume of osmotic water removal per gram absorbed glucose) will be determined (in mL/gram absorbed glucose).	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Removal of urea by the WEAKID system	The removal of urea (in mmol) by the WEAKID system will be determined for each WEAKID treatment	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Removal of creatinine by the WEAKID system	The removal of creatinine (in mmol) by the WEAKID system will be determined for each WEAKID treatment	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Removal of phosphate by the WEAKID system	The removal of phosphate (in mmol) by the WEAKID system will be determined for each WEAKID treatment	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Removal of potassium by the WEAKID system	The removal of potassium (in mmol) by the WEAKID system will be determined for each WEAKID treatment	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Removal of beta-2 microglobulin by the WEAKID system	The removal of beta-2 microglobulin (in mmol) by the WEAKID system will be determined for each WEAKID treatment	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Mass transfer area coefficient of urea	The mass transfer area coefficient (MTAC) for urea will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Mass transfer area coefficient of creatinine	The mass transfer area coefficient (MTAC) for creatinine will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Mass transfer area coefficient of phosphate	The mass transfer area coefficient (MTAC) for phosphate will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Mass transfer area coefficient of potassium	The mass transfer area coefficient (MTAC) for potassium will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Mass transfer area coefficient of beta-2 microglobulin	The mass transfer area coefficient (MTAC) for beta-2 microglobulin will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Plasma clearance of urea	The plasma clearance of urea will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Plasma clearance of creatinine	The plasma clearance of creatinine will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Plasma clearance of phosphate	The plasma clearance of phosphate will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Plasma clearance of potassium	The plasma clearance of potassium will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Plasma clearance of beta-2 microglobulin	The plasma clearance of beta-2 microglobulin will be determined for each WEAKID treatment (in mL/min)	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
The plasma reduction ratio of the protein-bound uremic toxin p-cresyl sulfate	The plasma reduction ratio of p-cresyl sulfate will be calculated using the plasma concentrations before and after each WEAKID treatment.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
The plasma reduction ratio of the protein-bound uremic toxin p-cresyl glucuronide	The plasma reduction ratio of p-cresyl glucuronide will be calculated using the plasma concentrations before and after WEAKID treatment.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
The plasma reduction ratio of the protein-bound uremic toxin indole acetic acid	The plasma reduction ratio of indole acetic acid will be calculated using the plasma concentrations before and after WEAKID treatment.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
The plasma reduction ratio of the protein-bound uremic toxin kynurenine	The plasma reduction ratio of kynurenine will be calculated using the plasma concentrations before and after WEAKID treatment.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
The plasma reduction ratio of the protein-bound uremic toxin kynurenic acid	The plasma reduction ratio of kynurenic acid will be calculated using the plasma concentrations before and after WEAKID treatment.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
The plasma reduction ratio of the protein-bound uremic toxin hippuric acid	The plasma reduction ratio of hippuric acid will be calculated using the plasma concentrations before and after WEAKID treatment.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
The release of base	The release of base (in mmol) will be determined by calculating the sum of the release of bicarbonate (in mmol) and that of lactate (in mmol) for each WEAKID treatment	This will be assessed for every WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of urea	Urea plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of creatinine	Creatinine plasma levels (in micromol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of uric acid	Uric acid plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of beta-2 microglobulin	Beta-2 microglobulin plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of phosphate	Phosphate plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of potassium	Potassium plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of bicarbonate	Bicarbonate plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of lactate	Lactate plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of sodium	Sodium plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of chloride	Chloride plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of calcium	Calcium plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of magnesium	Magnesium plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of glucose	Glucose plasma levels (in mmol/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of lactate dehydrogenase	Lactate dehydrogenase plasma levels (in U/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of vitamin B12	Vitamin B12 plasma levels (in mg/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of albumin	Albumin plasma levels (in g/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma leucocyte count	Leucocyte count in plasma (in x10^9/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma thrombocyte count	Thrombocyte count in plasma (in x10^9/L) will be determined before and after every WEAKID session.	These will be assessed before (at t=0 minutes) and after (at t=240 minutes or t=480 minutes for the 4-hour and 8-hour treatment, respectively) the WEAKID treatment throughout the study treatment period (2 weeks in total per participant)
Evolution of plasma levels of C-reactive protein (CRP)	CRP plasma levels (in mg/L) will be determined before and after every series of three WEAKID sessions.	This will be assessed before and after every series of three WEAKID treatment throughout the study treatment period (two times per week, two weeks in total per participant)
Evolution of plasma levels of bilirubin	Bilirubin plasma levels (in umol/L) will be determined before and after every series of three WEAKID sessions.	This will be assessed before and after every series of three WEAKID treatment throughout the study treatment period (two times per week, two weeks in total per participant)
Evolution of plasma levels of aspartate transaminase (ASAT)	ASAT plasma levels (in U/L) will be determined before and after every series of three WEAKID sessions.	This will be assessed before and after every series of three WEAKID treatment throughout the study treatment period (two times per week, two weeks in total per participant)
Evolution of plasma levels of alanine aminotransferase (ALAT)	ALAT plasma levels (in U/L) will be determined before and after every series of three WEAKID sessions.	This will be assessed before and after every series of three WEAKID treatment throughout the study treatment period (two times per week, two weeks in total per participant)
Evolution of sodium levels in dialysate effluent	Sodium levels (in mmol/L) will be determined in dialysate effluent at various timepoints during every WEAKID treatment.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of chloride levels in dialysate effluent	Chloride levels (in mmol/L) will be determined in dialysate effluent at various timepoints during every WEAKID treatment.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of calcium levels in dialysate effluent	Calcium levels (in mmol/L) will be determined in dialysate effluent at various timepoints during every WEAKID treatment.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of magnesium levels in dialysate effluent	Magnesium levels (in mmol/L) will be determined in dialysate effluent at various timepoints during every WEAKID treatment.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of bicarbonate levels in dialysate effluent	Bicarbonate levels (in mmol/L) will be determined in dialysate effluent at various timepoints during every WEAKID treatment.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of lactate levels in dialysate effluent	Lactate levels (in mmol/L) will be determined in dialysate effluent at various timepoints during every WEAKID treatment.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Evolution of pH of dialysate effluent	pH of dialysate effluent will be determined at various timepoints during every WEAKID treatment.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Total number of device deficiencies and adverse device effects	All device deficiencies (DDs) and adverse device effects (ADEs) will be reported and quantified.	This will be assessed through study completion (four weeks in total per participant)
Evolution of delta intraperitoneal pressure during WEAKID treatment	Delta intraperitoneal pressure will be calculated using the following formula: intraperitoneal pressure during WEAKID treatment (in mbar) - intraperitoneal pressure at t=0 (in mbar). Intraperitoneal pressure is determined using the pressure sensors of the WEAKID device.	This will be assessed during WEAKID treatment at t=15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours (for 8-hour treatment), and 8 hours (for 8-hour treatment) throughout the study treatment period (2 weeks in total per participant)
Patient tolerance (abdominal discomfort)	Abdominal discomfort (scored using a numeric rating scale between 0-10) will be determined multiple times throughout the study period.	This will be assessed at baseline, during every WEAKID treatment (at t = 0 minutes, 15 minutes, 1 hour, 2 hours, 4 hours, and 8 hours (for 8-hour treatment), and at the end of the study period (4 weeks in total per participant).
Evolution of uremic symptoms	Uremic symptoms will be scored using the Dialysis Symptom Index questionnaire; this is a questionnaire consisting of thirty yes/no questions regarding whether participants have experienced a certain symptom during the last week. If the answer is yes, the participant will score how much they have felt burdened by this specific symptom during the last week on a Likert scale from 0-4; the higher the score, the more burdened the participant felt.	This will be assessed at baseline and on the day of the last WEAKID treatment of each treatment week (three times during three weeks in total per participant).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline characteristics	At baseline, demographical, clinical, and laboratory data will be collected. These include age, gender, body mass index, blood pressure, heart rate, oxygen saturation, body temperature, medication usage, medical history (including cause of kidney failure and comorbidity scored using the Charlsons' and Davies' indices, residual kidney function, renal clearance, renal weekly Kt/V, estimated glomerular filtration rate, and dialysis-related data (duration of dialysis, PD treatment modality and scheme, peritoneal catheter type, history of peritoneal catheter dysfunction or infection, dialysis adequacy, and peritoneal weekly Kt/V.	These will be assessed at baseline
Peritoneal equilibrium tests	The standard peritoneal membrane analysis will be performed to determine the function of the peritoneal membrane.	This will be assessed once at baseline and once the week after the last WEAKID treatment week (four weeks in total per participant).

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Health Holland; Dutch Kidney Foundation; Horizon 2020 - European Commission; Servicio Madrileño de Salud (SERMAS); Nanodialysis Ltd; Università degli studi di Modena e Reggio Emilia (UNIMORE); PPI Healthcare Consulting Ltd
• Investigators: Principal Investigator: Karin GF Gerritsen, MD, PhD, UMC Utrecht

Publications and helpful links

General Publications

• van Gelder MK, Ligabue G, Giovanella S, Bianchini E, Simonis F, Hazenbrink DHM, Joles JA, Bajo Rubio MA, Selgas R, Cappelli G, Gerritsen KGF. In vitro efficacy and safety of a system for sorbent-assisted peritoneal dialysis. Am J Physiol Renal Physiol. 2020 Aug 1;319(2):F162-F170. doi: 10.1152/ajprenal.00079.2020. Epub 2020 Jun 1.
• van Gelder MK, de Vries JC, Simonis F, Monninkhof AS, Hazenbrink DHM, Ligabue G, Giovanella S, Joles JA, Verhaar MC, Bajo Rubio MA, Selgas R, Cappelli G, Gerritsen KGF. Evaluation of a system for sorbent-assisted peritoneal dialysis in a uremic pig model. Physiol Rep. 2020 Dec;8(23):e14593. doi: 10.14814/phy2.14593.

Helpful Links

• Website regarding project CORDIAL

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 1, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 15, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Peritoneal Dialysis; First-in-human; Medical device
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency, Chronic
• Other Study ID Numbers: 23-075_CORDIAL_FIH; NL83843.000.23 (Other Identifier: CCMO (Centrale Commissie Mensgebonden Onderzoek))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Raw data will only be available to other researchers upon request and after approval of the Principal Investigator since the data is privacy-sensitive (pseudonymized) and commercially sensitive.

IPD Sharing Time Frame

The following data will be shared (under restrictions if seen fit by the Principal Investigator) upon request:

• The raw data
• The study protocol describing the methods and materials
• The script to process the data
• The scripts leading to tables and figures in the publication
• A codebook with explanations on the variable names
• A 'read_me.txt' file with an overview of files included and their content and use.

The time period will be determined on a case-by-case basis. A data sharing agreement outlining the terms of use for the receiving party will be drawn up before data is transferred.

• IPD Sharing Access Criteria: Data will be shared upon request after approval from the PI. The access criteria will be determined on a case-by-case basis.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No