Use of Direct Peritoneal Resuscitation in High-risk Liver Transplant Recipients

Obesity Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05195125
• Other study ID #: 21-4214
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 1, 2022
• Est. completion date: December 2023

Study information

• Verified date: June 2023
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: December 2023
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• End Stage Liver DIsease
• Liver Diseases
• Obesity

Intervention

Procedure:
• Direct Peritoneal Resuscitation
Direct peritoneal resuscitation involves the abdominal infusion and drainage of a peritoneal dialysate in high-risk liver transplant patients, for up to 24 hours after surgery.

Locations

Country	Name	City	State
United States	UCHealth - Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients that complete DPR infusion without reaching stopping criteria		Up to 24 hours after initiation of direct peritoneal resuscitation
Secondary	Rate of return to the operating room after index operation	Amount of patients that require a re-operation after their transplant	Up to 7 days after transplant
Secondary	Abdominal compartment syndrome requiring reoperation	Number of patients that develop increased intraabdominal pressure as a consequence of dialysate infusion	Events that occur during the duration of the DPR infusion, which will last no more than 24 hours after the participant's transplant surgery.
Secondary	Percent of patients that complete DPR infusion		Up to 24 hours after initiation of DPR
Secondary	Percent of patients that are transferred to hospital ward	Patients that are admitted to the hospital ward after surgery, not requiring ICU admission	Up to 24 hours after surgery
Secondary	Rate of early allograft dysfunction	Patients who experience slow function of their transplanted liver after their transplant	Up to 7 days after transplant
Secondary	Number of blood product units required during first 24 hours postoperatively	The study team will record the number of units of blood product (i.e. "bags" of red blood cells, platelets, etc.) required by the participant in the first day after liver transplantation.	Up to 24 hours after transplant
Secondary	Number of participants that require renal replacement therapy (i.e. hemodialysis) during the first 7 days after liver transplant.	Researches will record whether the participant developed renal failure requiring renal replacement therapy (i.e. hemodialysis)	Up to 7 days after transplant
Secondary	Hourly urine output for first 24 hours		Up to 24 hours after transplant
Secondary	Rate of early infection after transplant	Researchers will record any infections that participants develop after transplantation. These may include abscess, peritonitis, bacteremia, and pneumonia.	<7 days postoperatively
Secondary	Rate of late infection after transplant	Researchers will record any infections that participants develop after transplantation. These may include abscess, peritonitis, bacteremia, and pneumonia.	7-30 days postoperatively
Secondary	Rate of mechanical bowel obstruction	Constipation caused by compression from inside or outside of the bowel lumen	Up to 30 days after transplant
Secondary	Ileus/time to oral intake	Time to return of normal bowel function and food tolerance after transplant	Up to 30 days after transplant
Secondary	Duration of insulin infusion post-operatively	Insulin requirements after transplant surgery	Up to 7 days after transplant
Secondary	Ventilator free days	Outcome measurement that looks into rate of respiratory failure requiring prolonged mechanical ventilation after transplant surgery	Up to 28 days post-op

External Links

•   Addition of direct peritoneal lavage to human cadaver organ donor resuscitation improves organ procurement.
•   Direct peritoneal resuscitation accelerates primary abdominal wall closure after damage control surgery.
•   Direct Peritoneal Resuscitation Alters Hepatic miRNA Expression after Hemorrhagic Shock.
•   Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation.
•   Direct peritoneal resuscitation improves inflammation, liver blood flow, and pulmonary edema in a rat model of acute brain death.
•   Direct Peritoneal Resuscitation: A review.