Clinical trial NCT05195125: Use of Direct Peritoneal Resuscitation in High-risk Liver Transplant Recipients
Official title: Phase I Clinical Trial Utilizing Direct Peritoneal Resuscitation in Liver Transplant Recipient Population at Increased Risk of Return to the Operating Room and Early Allograft Dysfunction
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: End Stage Liver DIsease
Obesity
Acute Kidney Injury
Keywords: Liver transplant
Obesity
Renal failure
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2022-01-18
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All study subjects will be enrolled to the treatment arm
Primary purpose: PREVENTION

Brief summary: This study is being conducted to assess the safety of Direct Peritoneal Resuscitation (DPR) in high-risk liver transplant patients. The investigators want to also identify if this method of recovery after large surgery has the same benefits in liver transplant patients as have been appreciated in other surgical patients. The combination of elevated BMI and impaired kidney function increases the risk of 1) needing intensive care unit (ICU) admission after surgery, 2) slow function of the new liver \[technically termed Early Allograft Dysfunction (EAD)\] and 3) need for more than one operation. The study team also aims to identify if DPR can reduce these risks and not cause other unexpected complications following surgery. DPR involves the infusion of a solution into the abdomen and has been shown to reduce edema and improve blood flow in organs. The solution used in this study is a commercially available peritoneal dialysate, a dextrose containing solution that is infused into the abdominal cavity and is routinely used in patients with end-stage renal disease requiring dialysis.

Detailed description: The central hypothesis of this study is that direct peritoneal resuscitation is a safe therapy following liver transplantation and is associated with a reduced rate of return to the operating room.

AIM 1: Determine the safety profile of direct peritoneal resuscitation on liver transplant recipients at risk of return to the operating room and ICU admission. Hypothesis: Liver transplant recipients that receive DPR will have comparable complication rates to historic controls of liver transplant recipients with similar demographics.

AIM 2: Identify if direct peritoneal resuscitation demonstrates a trend towards a reduced rate of return to the operating room compared to historic controls. Hypothesis: DPR will demonstrate a trend of a reduce rate of return to the operating room of liver transplant patients after index operation compared to historic controls.

AIM 3: Identify if direct peritoneal resuscitation reduces the rate of early allograft dysfunction and other organ failure following liver transplantation with interval improvement in post-operative fibrinolysis activity. Hypothesis: DPR will reduce the rate of EAD of liver transplant patients compared to historic controls and is associated with increased fibrinolysis in the post-operative period.

Eligibility criteria: Inclusion Criteria:

* Adult liver transplant recipients ≥18 y/o
* Ability to consent
* Pre-operative Creatinine ≥1.1 (or on dialysis) and BMI ≥30

Exclusion Criteria:

* Diaphragmatic injury
* Active spontaneous bacterial peritonitis (SBP) with initiation of antibiotic treatment within 72 hours of surgery

Primary outcomes:
measure: Percent of patients that complete DPR infusion without reaching stopping criteria
timeFrame: Up to 24 hours after initiation of direct peritoneal resuscitation
Secondary outcomes:
measure: Rate of return to the operating room after index operation
timeFrame: Up to 7 days after transplant
measure: Abdominal compartment syndrome requiring reoperation
timeFrame: Events that occur during the duration of the DPR infusion, which will last no more than 24 hours after the participant's transplant surgery.
measure: Percent of patients that complete DPR infusion
timeFrame: Up to 24 hours after initiation of DPR
measure: Percent of patients that are transferred to hospital ward
timeFrame: Up to 24 hours after surgery
measure: Rate of early allograft dysfunction
timeFrame: Up to 7 days after transplant
measure: Number of blood product units required during first 24 hours postoperatively
timeFrame: Up to 24 hours after transplant
measure: Number of participants that require renal replacement therapy (i.e. hemodialysis) during the first 7 days after liver transplant.
timeFrame: Up to 7 days after transplant
measure: Hourly urine output for first 24 hours
timeFrame: Up to 24 hours after transplant
measure: Rate of early infection after transplant
timeFrame: <7 days postoperatively
measure: Rate of late infection after transplant
timeFrame: 7-30 days postoperatively
measure: Rate of mechanical bowel obstruction
timeFrame: Up to 30 days after transplant
measure: Ileus/time to oral intake
timeFrame: Up to 30 days after transplant
measure: Duration of insulin infusion post-operatively
timeFrame: Up to 7 days after transplant
measure: Ventilator free days
timeFrame: Up to 28 days post-op
Other outcomes:
Locations:
city: Aurora
country: United States
facility: UCHealth - Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado School of Medicine
name: Hunter B Moore, M.D., P.hD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weaver JL, Smith JW. Direct Peritoneal Resuscitation: A review. Int J Surg. 2016 Sep;33(Pt B):237-241. doi: 10.1016/j.ijsu.2015.09.037. Epub 2015 Sep 16.
citation: Smith JW, Garrison RN, Matheson PJ, Franklin GA, Harbrecht BG, Richardson JD. Direct peritoneal resuscitation accelerates primary abdominal wall closure after damage control surgery. J Am Coll Surg. 2010 May;210(5):658-64, 664-7. doi: 10.1016/j.jamcollsurg.2010.01.014.
citation: Zakaria el R, Garrison RN, Kawabe T, Harris PD. Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation. J Trauma. 2005 Mar;58(3):499-506; discussion 506-8. doi: 10.1097/01.ta.0000152892.24841.54.
citation: Smith JW, Ghazi CA, Cain BC, Hurt RT, Garrison RN, Matheson PJ. Direct peritoneal resuscitation improves inflammation, liver blood flow, and pulmonary edema in a rat model of acute brain death. J Am Coll Surg. 2014 Jul;219(1):79-87. doi: 10.1016/j.jamcollsurg.2014.03.045. Epub 2014 Apr 5.
citation: Weaver JL, Matheson PJ, Hurt RT, Downard CD, McClain CJ, Garrison RN, Smith JW. Direct Peritoneal Resuscitation Alters Hepatic miRNA Expression after Hemorrhagic Shock. J Am Coll Surg. 2016 Jul;223(1):68-75. doi: 10.1016/j.jamcollsurg.2016.03.024. Epub 2016 Mar 26.
citation: Smith JW, Matheson PJ, Morgan G, Matheson A, Downard C, Franklin GA, Garrison RN. Addition of direct peritoneal lavage to human cadaver organ donor resuscitation improves organ procurement. J Am Coll Surg. 2015 Apr;220(4):539-47. doi: 10.1016/j.jamcollsurg.2014.12.056. Epub 2015 Feb 9.