Intraoperative Dialysis in Liver Transplantation (INCEPTION)

• ClinicalTrials.gov Identifier: NCT01575015
• Recruitment Status: Terminated
• First Posted: April 10, 2012
• Last Update Posted: February 7, 2017
• Sponsor: University of Alberta
• Information provided by (Responsible Party): Sean M Bagshaw, University of Alberta

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Liver Failure; Acute Kidney Disease; Multi-organ Failure	Device: Continuous renal replacement therapy (CRRT); Procedure: Standard intraoperative support	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intra-Operative Continuous Renal Replacement Therapy in Liver Transplantation: A Phase II Randomized Controlled Trial (INCEPTION)
• Study Start Date: May 2012
• Actual Primary Completion Date: December 11, 2015
• Actual Study Completion Date: December 11, 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard intraoperative support (no CRRT)	Procedure: Standard intraoperative support; Patients allocated to standard intraoperative support will receive usual care (no CRRT).
Experimental: Intraoperative renal support (CRRT)	Device: Continuous renal replacement therapy (CRRT); Patients allocated with intraoperative CRRT will have a dialysis catheter inserted and receive CRRT during liver transplantation

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Fluid balance [ Time Frame: In-hospital (patients will be followed for duration of post-operative hospital stay, anticipated average 4 weeks post-operatively) ]
   Will be defined as the changes in fluid accumulation intra- and post-operatively.
2. Number of patients with post-operative graft dysfunction [ Time Frame: In-hospital (patients will be followed for duration of post-operative hospital stay, anticipated average 4 weeks post-operatively) ]
   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.
3. Number of patients with post-operative kidney dysfunction [ Time Frame: From the date of liver transplant until the date of first documented outcome of interest, assessed until 90-days ]
   Will be defined as post-operative acute kidney injury, defined by RIFLE criteria; along with encompassing receipt of renal replacement therapy (RRT).
4. Length of stay [ Time Frame: From the date of liver transplant until the date of discharge from ICU/hospital ]
   Will include ICU and hospital lengths of stay
5. Mortality [ Time Frame: From the date of liver transplant until the date of first documented outcome of interest, assessed until 90-days ]
   Mortality through 90-days.
6. Number of patients readmitted to hospital within 90-days [ Time Frame: From the date of liver transplant after hospital discharge, until the date of first documented re-admission to hospital, assessed until 90-days ]
   Will be defined as hospital re-admission within 90-days of liver transplant for any cause.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

Division of Critical Care Medicine, University of Alberta Hospital

Edmonton, Alberta, Canada, T6G2B7

Sponsors and Collaborators

University of Alberta

Investigators

• Principal Investigator: Sean M Bagshaw, MD, MSc; Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta

More Information

Publications:

Townsend DR, Bagshaw SM, Jacka MJ, Bigam D, Cave D, Gibney RT. Intraoperative renal support during liver transplantation. Liver Transpl. 2009 Jan;15(1):73-8. doi: 10.1002/lt.21650.

Parmar A, Bigam D, Meeberg G, Cave D, Townsend DR, Gibney RT, Bagshaw SM. An evaluation of intraoperative renal support during liver transplantation: a matched cohort study. Blood Purif. 2011;32(3):238-48. doi: 10.1159/000329485. Epub 2011 Aug 9.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karvellas CJ, Taylor S, Bigam D, Kneteman NM, Shapiro AMJ, Romanovsky A, Gibney RTN, Townsend DR, Meeberg G, Özelsel T, Bishop E, Bagshaw SM. Intraoperative continuous renal replacement therapy during liver transplantation: a pilot randomized-controlled trial (INCEPTION). Can J Anaesth. 2019 Oct;66(10):1151-1161. doi: 10.1007/s12630-019-01454-0. Epub 2019 Jul 26.

• Responsible Party: Sean M Bagshaw, Assistant Professor, University of Alberta
• ClinicalTrials.gov Identifier: NCT01575015
• Other Study ID Numbers: UOFAPro00026047
• First Posted: April 10, 2012
• Last Update Posted: February 7, 2017
• Last Verified: February 2017

Keywords provided by Sean M Bagshaw, University of Alberta:

Liver transplantation (E04.210.650); Renal replacement therapy (E05.196.353); Intra-operative period (E04.614.374); Safety (N06.850.135.060.075); Efficacy

Additional relevant MeSH terms:

Liver Failure; Kidney Diseases; Multiple Organ Failure; Urologic Diseases; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Shock; Pathologic Processes