End Stage Liver DIseasePhase 1NCT05195125
Use of Direct Peritoneal Resuscitation in High-risk Liver Transplant Recipients
A Phase 1 study testing Direct Peritoneal Resuscitation in people with End Stage Liver DIsease and Obesity, run by University of Colorado, Denver at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End Stage Liver DIsease, Obesity, Acute Kidney Injury
- What is being tested?
- Direct Peritoneal Resuscitation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2022to Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult liver transplant recipients ≥18 y/o
- Ability to consent
- Pre-operative Creatinine ≥1.1 (or on dialysis) and BMI ≥30
Who cannot join
- Diaphragmatic injury
- Active spontaneous bacterial peritonitis (SBP) with initiation of antibiotic treatment within 72 hours of surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
UCHealth - Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
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
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.
Read the 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.
- Conditions
- End Stage Liver DIsease, Obesity, Acute Kidney Injury
- Being tested
- Direct Peritoneal Resuscitation
- Keywords
- Liver transplant, Obesity, Renal failure
- Medical subject headings
- End Stage Liver Disease, Obesity, Acute Kidney Injury, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct Peritoneal ResuscitationProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Direct Peritoneal Resuscitation (DPR) Group | Experimental | At the time of abdominal closure and determination that the patient will either go to extended stay or the intensive care unit, three drains will be placed per standard of care. An additional 19 French drain will be placed at the ligament of Treitz at the base of the mesentery. Following abdominal closure DPR will be initiated with commercially available 2.5% glucose-based peritoneal dialysis solution at a rate of 1.5 cc/kg/hr based on previously reported therapy in trauma. Drains will be connected to continuous wall suction. This infusion will continue for the duration the patients stay in extended stay (8 hours) if they are deemed eligible for hospital ward admission, or for 24 hours if requiring ICU care. These patients will then be observed for their hospital course and monitored for outcomes listed above. Receives: Procedure: Direct Peritoneal Resuscitation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of patients that complete DPR infusion without reaching stopping criteria
Measured: Up to 24 hours after initiation of direct peritoneal resuscitation
Secondary outcomes (14)
Rate of return to the operating room after index operation
Amount of patients that require a re-operation after their transplant
Measured: Up to 7 days after transplant
Abdominal compartment syndrome requiring reoperation
Number of patients that develop increased intraabdominal pressure as a consequence of dialysate infusion
Measured: Events that occur during the duration of the DPR infusion, which will last no more than 24 hours after the participant's transplant surgery.
Percent of patients that complete DPR infusion
Measured: Up to 24 hours after initiation of DPR
Percent of patients that are transferred to hospital ward
Patients that are admitted to the hospital ward after surgery, not requiring ICU admission
Measured: Up to 24 hours after surgery
Rate of early allograft dysfunction
Patients who experience slow function of their transplanted liver after their transplant
Measured: Up to 7 days after transplant
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.
Measured: Up to 24 hours after transplant
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)
Measured: Up to 7 days after transplant
Hourly urine output for first 24 hours
Measured: Up to 24 hours after transplant
Rate of early infection after transplant
Researchers will record any infections that participants develop after transplantation. These may include abscess, peritonitis, bacteremia, and pneumonia.
Measured: <7 days postoperatively
Rate of late infection after transplant
Researchers will record any infections that participants develop after transplantation. These may include abscess, peritonitis, bacteremia, and pneumonia.
Measured: 7-30 days postoperatively
Rate of mechanical bowel obstruction
Constipation caused by compression from inside or outside of the bowel lumen
Measured: Up to 30 days after transplant
Ileus/time to oral intake
Time to return of normal bowel function and food tolerance after transplant
Measured: Up to 30 days after transplant
Duration of insulin infusion post-operatively
Insulin requirements after transplant surgery
Measured: Up to 7 days after transplant
Ventilator free days
Outcome measurement that looks into rate of respiratory failure requiring prolonged mechanical ventilation after transplant surgery
Measured: Up to 28 days post-op
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2022
- Study start1 Feb 2022
- Primary completionAug 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for End Stage Liver DIseaseStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All study subjects will be enrolled to the treatment arm
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hunter B Moore, M.D., P.hD., Principal investigator, University of Colorado School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05195125
- Sponsor's protocol ID
- 21-4214
- Status last verified
- Jun 2023
- First submitted
- 14 Dec 2021
- Last updated
- 8 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26384838Smith 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.
PubMed 20421025Zakaria 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.
PubMed 15761343Smith 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.
PubMed 24952444Weaver 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.
PubMed 27345902Smith 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.
PubMed 25797737
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05195125
- Acronym / sponsor ID
- 21-4214
- Conditions
- End Stage Liver DIsease, Obesity, Acute Kidney Injury
- Keywords
- Liver transplant, Obesity, Renal failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- Aug 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 18 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All study subjects will be enrolled to the treatment arm
| Arm | Type | Receives |
|---|---|---|
| Direct Peritoneal Resuscitation (DPR) Group | Experimental | Procedure: Direct Peritoneal ResuscitationAt the time of abdominal closure and determination that the patient will either go to extended stay or the intensive care unit, three drains will be placed per standard of care. An additional 19 French drain will be placed at the ligament of Treitz at the base of the mesentery. Following abdominal closure DPR will be initiated with commercially available 2.5% glucose-based peritoneal dialysis solution at a rate of 1.5 cc/kg/hr based on previously reported therapy in trauma. Drains will be connected to continuous wall suction. This infusion will continue for the duration the patients stay in extended stay (8 hours) if they are deemed eligible for hospital ward admission, or for 24 hours if requiring ICU care. These patients will then be observed for their hospital course and monitored for outcomes listed above. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult liver transplant recipients ≥18 y/o
- Ability to consent
- Pre-operative Creatinine ≥1.1 (or on dialysis) and BMI ≥30
Key exclusion criteria (2 listed)
- Diaphragmatic injury
- Active spontaneous bacterial peritonitis (SBP) with initiation of antibiotic treatment within 72 hours of surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Direct Peritoneal ResuscitationDirect 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. | Procedure or surgery | Direct Peritoneal Resuscitation (DPR) Group |
Primary outcome
Percent of patients that complete DPR infusion without reaching stopping criteria
Time frame: Up to 24 hours after initiation of direct peritoneal resuscitation
14 secondary outcomes
Rate of return to the operating room after index operation
Time frame: Up to 7 days after transplant
Abdominal compartment syndrome requiring reoperation
Time frame: Events that occur during the duration of the DPR infusion, which will last no more than 24 hours after the participant's transplant surgery.
Percent of patients that complete DPR infusion
Time frame: Up to 24 hours after initiation of DPR
Percent of patients that are transferred to hospital ward
Time frame: Up to 24 hours after surgery
Rate of early allograft dysfunction
Time frame: Up to 7 days after transplant
Number of blood product units required during first 24 hours postoperatively
Time frame: Up to 24 hours after transplant
Number of participants that require renal replacement therapy (i.e. hemodialysis) during the first 7 days after liver transplant.
Time frame: Up to 7 days after transplant
Hourly urine output for first 24 hours
Time frame: Up to 24 hours after transplant
Rate of early infection after transplant
Time frame: <7 days postoperatively
Rate of late infection after transplant
Time frame: 7-30 days postoperatively
Rate of mechanical bowel obstruction
Time frame: Up to 30 days after transplant
Ileus/time to oral intake
Time frame: Up to 30 days after transplant
Duration of insulin infusion post-operatively
Time frame: Up to 7 days after transplant
Ventilator free days
Time frame: Up to 28 days post-op
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2023.
- Background: PubMed 26384838Weaver 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.
- Background: PubMed 20421025Smith 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.
- Background: PubMed 15761343Zakaria 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.
- Background: PubMed 24952444Smith 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.
- Background: PubMed 27345902Weaver 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.
- Background: PubMed 25797737Smith 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.
- Direct Peritoneal Resuscitation: A review.Link provided by the sponsor.
- Direct peritoneal resuscitation accelerates primary abdominal wall closure after damage control surgery.Link provided by the sponsor.
- Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation.Link provided by the sponsor.
- Direct peritoneal resuscitation improves inflammation, liver blood flow, and pulmonary edema in a rat model of acute brain death.Link provided by the sponsor.
- Direct Peritoneal Resuscitation Alters Hepatic miRNA Expression after Hemorrhagic Shock.Link provided by the sponsor.
- Addition of direct peritoneal lavage to human cadaver organ donor resuscitation improves organ procurement.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hunter B Moore, M.D., P.hD. principal investigator
University of Colorado School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Direct Peritoneal Resuscitation in people with End Stage Liver DIsease and Obesity, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of patients that complete DPR infusion without reaching stopping criteria (time frame: Up to 24 hours after initiation of direct peritoneal resuscitation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05195125, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2023.