Intraoperative Dialysis in Liver Transplantation

Study Overview
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Brief Summary
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Patient with liver failure waiting for liver transplantation are often hospitalized and commonly supported in an intensive care unit prior to surgery. These patients are sick, and in addition to the complications of a failing liver, other organs such as the kidneys often fail as well. As a consequence, these patients are at an increased risk for complications related to their kidney failure during their liver transplantation procedure. One potential method to diminish the risk of these complications is to provide dialysis support to these patients during their liver transplantation in the operating theater in the form of continuous renal replacement therapy (CRRT). While this is increasingly being performed and is theoretically appealing, there is very little information to support this practice. In addition, the use of CRRT during surgery is not entirely without risk. The investigators have performed two preliminary studies on the use of CRRT during liver transplantation and our data would strongly support the need to conduct further higher-quality studies to better evaluate its feasibility, safety and usefulness. Our proposed study is for a randomized trial comparing the use of CRRT during surgery with standard supportive care in sick patients with liver failure scheduled to receive a liver transplantation.

Official Title
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Intra-Operative Continuous Renal Replacement Therapy in Liver Transplantation: A Phase II Randomized Controlled Trial (INCEPTION)

Conditions
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Liver Failure, Acute Kidney Disease, Multi-organ Failure

Intervention / Treatment
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* Device: Continuous renal replacement therapy (CRRT)
* Procedure: Standard intraoperative support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consent Adult (age > 18 years on the day of assessment of eligibility) Planned cadaveric orthotopic liver transplantation Pre-operative unadjusted (natural) Modification of End-Stage Liver Disease (MELD) score > 25. Pre-operative AKI, defined by a minimum RIFLE-RISK, AND/OR pre-operative estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2, calculated by the Modification of Diet in Renal Disease (MDRD) equation. Exclusion Criteria: Planned living-related donor liver transplantation Pre-operative potassium [K] > 4.5 mmol/L AND urine output < 100 mL in the 6 hrs preceding assessment of eligibility Pre-operative pH < 7.3

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard intraoperative support (no CRRT)<br> | Procedure: Standard intraoperative support<br>* Patients allocated to standard intraoperative support will receive usual care (no CRRT).<br>|
| Experimental: Intraoperative renal support (CRRT)<br> | Device: Continuous renal replacement therapy (CRRT)<br>* Patients allocated with intraoperative CRRT will have a dialysis catheter inserted and receive CRRT during liver transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients adhering to the prescribed protocol | Will be defined as the proportion of patients adhering to the prescribed protocol. | Intra-operative (From the induction of anesthesia to trasnfer from the OR to the ICU, average 6-8 hours) | 
| Number of patients with adverse events | This will be defined by the proportion of patients experiencing intra-operative adverse events, serious adverse events and complications related to the study intervention. | Intra-operative (From the induction of anesthesia to trasnfer from the OR to the ICU, average 6-8 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid balance | Will be defined as the changes in fluid accumulation intra- and post-operatively. | In-hospital (patients will be followed for duration of post-operative hospital stay, anticipated average 4 weeks post-operatively) | 
| Number of patients with post-operative graft dysfunction | Graft dysfunction will include post-operative ultrasonographic-evidence of vascular ischemia/occlusion or venous occlusion; biliary stricture, obstruction or anastomosis leak; primary non-function; biopsy-proven rejection; or need for surgical re-exploration for any reason. | In-hospital (patients will be followed for duration of post-operative hospital stay, anticipated average 4 weeks post-operatively) | 
| Number of patients with post-operative kidney dysfunction | Will be defined as post-operative acute kidney injury, defined by RIFLE criteria; along with encompassing receipt of renal replacement therapy (RRT). | From the date of liver transplant until the date of first documented outcome of interest, assessed until 90-days | 
| Length of stay | Will include ICU and hospital lengths of stay | From the date of liver transplant until the date of discharge from ICU/hospital | 
| Mortality | Mortality through 90-days. | From the date of liver transplant until the date of first documented outcome of interest, assessed until 90-days | 
| Number of patients readmitted to hospital within 90-days | Will be defined as hospital re-admission within 90-days of liver transplant for any cause. | From the date of liver transplant after hospital discharge, until the date of first documented re-admission to hospital, assessed until 90-days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplantation (E04.210.650), Renal replacement therapy (E05.196.353), Intra-operative period (E04.614.374), Safety (N06.850.135.060.075), Efficacy