Evaluation of the Impact of the UPLUG Device Onto the Infection Rate of Indwelling Central Venous Catheters in Patients Undergoing Chronic Hemodialysis

Study Overview
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Brief Summary
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Infections are common complications among patients on chronic haemodialysis. Haemodialysis patients with a catheter have a 2- to 3-fold increased risk of hospitalization for infection and death compared with patients with an arteriovenous fistula or graft [0]. As it is a major concern for the medical community, this clinical investigation aims at assessing, in real world conditions, the impact of the UPLUG device onto the infection rate of indwelling central venous haemodialysis catheters. UPLUG-EVIDENCE is an international, multicenter, randomised, open label trial that will evaluate the efficacy of the UPLUG device on the reduction of bacterial infections in patients undergoing chronic haemodialysis with central venous catheter (CVC). The UPLUG device has been designed to : reduce the haemodialysis catheter openings, hence potentially reducing the infectious risk, improve the lock solution infusion using a positive pressure, limiting the thrombosis risk and associated haemodialysis catheter dysfunction limit the time needed to connect and disconnect the patient, by facilitating how the different steps are operated, and even allowing a connection/disconnection with a single healthcare professional ultimately enhance patient's autonomy with ergonomics & safe procedures

Detailed Description
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A total of 464 end stage renal disease patients undergoing chronic haemodialysis and receiving a new (de novo or replacement) indwelling CVC will be randomly assigned in a 1:1 ratio to perform either standard-of-care dialysis (232) or standard-of-care dialysis associated with the UPLUG device (232). The UPLUG device consists of 2 parts : the UPLUG Port, a sterile, single use device connected to the distal Luer-Lock connectors of a regular central venous catheter. It may be connected up to 29 days and the UPLUG Disposable, a sterile, single use device indicated for use with the UPLUG Port to perform a chronic haemodialysis therapy. it will be changed at every dialysis session. Treatment period (16 weeks): W1:D1 : first connection of the UPLUG Port The patient will be seen by a nurse or an investigator at D29, D57 and D85 for UPLUG port periodical replacement, and at D113 for the definitive withdrawal of the UPLUG port. Follow-up period (29 days): A last visit (onsite or call) is planned during the definitive withdrawal of the CVC or no later than 29 days after the end of the treatment period (D113) to assess the safety and well-being of the patient

Official Title
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EValuation of the Impact of the UPLUG DEvice Onto the iNfection Rate of Indwelling Central Venous Catheters in Patients Undergoing Chronic hEmodialysis

Conditions
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Renal Disease, Chronic, Hemodialysis Catheter Infection

Intervention / Treatment
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* Device: Connecting valve system
* Device: Central haemodialysis Venous Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: End-stage renal disease Chronic haemodialysis indwelling de novo or replacement central veinous catheter Exclusion Criteria: Life expectancy < 1 year Renal transplantation already scheduled at inclusion (living donor) Current infection of CVC percutaneous or subcutaneous site Pregnant or breastfeeding female, or women without a medically significant contraceptive regimen Patient with mechanical heart valve Patient with an AVF likely to be functional within 1 month Strictly more than 3 dialysis sessions a week Patient undergoing haemodialysis session > 4h30 Participation to another clinical study in the last 30 days period Patient unable to give a freely-given, written, informed consent Vulnerable participants

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-centered open labelled two-arm randomized (1:1) superiority trial. One arm will have standard dialysis, the other arm will have dialysis using the UPLUG device
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UPLUG Arm<br>Patients will have regular central veinous catheter and UPLUG device for their dialysis sessions. | Device: Connecting valve system<br>* UPLUG Port (changed every 29 days) and UPLUG Disposable (changed at every dialysis session) ensure the connection between a regular haemodialysis catheter and an extracorporeal circuit, and proceed to different steps of haemodialysis session without handling the Luer-Lock connectors of the haemodialysis catheter<br>* Other names: UPLUG Disposable;Device: Central haemodialysis Venous Catheter<br>* Central haemodialysis venous catheter (CE marked) will be used within the scope of their intended purpose during the dialysis session<br>|
| Other: Standard Of Care Arm<br>Patients will have regular central veinous catheter (standard of care) for their dialysis. | Device: Central haemodialysis Venous Catheter<br>* Central haemodialysis venous catheter (CE marked) will be used within the scope of their intended purpose during the dialysis session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of bacterial infection within the 16 weeks of treatment period | A clinical suspicion of bacterial infection is defined by : 1/ fever (T>37.5°C) or Or 2/ rigor Or 3/ new pre-HD hypotension (systolic arterial pressure <90mmHg) Or 4/ confusion and/or disorientation at the investigator's discretion and will lead to a confirmation of bacteraemia**: Blood culture (BC) growing the same organism from : 1/ HD catheter and 2a/ Peripheral vein And/or 2b/ Dialysis bloodline | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of clinical suspicion of bacterial infection during the 16 weeks of the treatment period, evaluated at Day 29, Day 57, Day 85 and Day 113 | A clinical suspicion of bacterial infection is defined by one of the following : 1/ fever (T>37.5°C) Or 2/ rigor Or 3/ new pre-HD hypotension (systolic arterial pressure <90mmHg) Or 4/ confusion and/or disorientation at the investigator's discretion | Day 29, Day 57, Day 85 and Day 113 | 
| Number of positive blood culture during the 16 weeks of the treatment period evaluated at Day 29, Day 57, Day 85 and Day 113 | Positive blood culture from one of the following : 1/ HD catheter Or 2/ Peripheral vein Or 3/ Dialysis bloodline | Day 29, Day 57, Day 85 and Day 113 | 
| Number of dysfunction estimated by blood flow rate (Qb) evaluated at Day 29, Day 57, Day 85 and Day 113 | Dysfunction is defined as: Qb < 200 ml/min during 30 minutes in the course of one haemodialysis session; Or Mean Qb < 250 ml/min during two consecutive haemodialysis sessions | Day 29, Day 57, Day 85 and Day 113 | 
| Number of adverse events during the 16 weeks of treatment period evaluated at D29, D57, D85 and D113 | Adverse events defined as defectiveness of the device, defectiveness of the placement, thrombosis events and infections | D29, D57, D85 and D113 | 
| Number of infections other than bacterial during the 16 weeks of treatment period evaluated at Day 29, Day 57, Day 85 and Day 113 | Infections other than bacterial : viral, fungal, parasitic | Day 29, Day 57, Day 85, Day 113 | 
| The patient satisfaction | Patient satisfaction is assessed through : a specific UBIPLUG questionnaire and a questionnaire SF-36 (Short-Form 36 Health Survey) | Day 1, Day 29, Day 57, Day 85, Day 113, Day 141 | 
| Number of patients with at least one bacterial infection during the 16 weeks of treatment period evaluated at Day 29, Day 57, Day 85 and Day 113 | A clinical suspicion of bacterial infection is defined by : 1/ fever (T>37.5°C) or Or 2/ rigor Or 3/ new pre-HD hypotension (systolic arterial pressure <90mmHg) Or 4/ confusion and/or disorientation at the investigator's discretion and will lead to a confirmation of bacteraemia: Blood culture (BC) growing the same organism from : 1/ HD catheter and 2a/ Peripheral vein And/or 2b/ Dialysis bloodline | Day 29, Day 57, Day 85, Day 113 | 
| Rate of infections other than bacterial evaluated at Day 29, Day 57, Day 85 and Day 113 | infections other than bacterial : viral, fungal, parasitic | Day 29, Day 57, Day 85, Day 113 | 
| Rate of unplanned hospitalisation at Day 113 and at the end of the study | Unplanned hospitalisation including less than 12 hours | Day 113, Day 141 | 
| Time spent by session by the nurse to connect the patient at Day 1, Day 29, Day 57, Day 85 and Day 113 | Measured time from the start of the catheter management to the start of the dialysis session | Day 1, Day 29, Day 57, Day 85, Day 113 | 
| The nurse satisfaction for the patients in UPLUG arm | Assessed through a specific UBIPLUG questionnaire | Day 1, Day 113 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central venous catheter, UPLUG, Infection