Effect Inhaled Nitric Oxide in Adult Liver Transplant

NCT07125443 | Not Yet Recruiting

• 1 other identifier: iNO for LT
• Study Type: interventional
• Target: 260
• Locations: 0 countries
• Sites: N/A

Brief Summary

Liver transplantation remains the only cure for patients with end-stage liver disease. Despite continuous advances in medical care, ischemia-reperfusion injury (IRI) (tissue damage that occurs when blood supply is restored to an area that has been deprived of oxygen) remains a major contributor to complications with the newly transplanted liver. IRI can lead to a condition known as post-reperfusion syndrome that involves profound narrowing of blood vessels, significantly low blood pressure, and an increased requirement of medication to control blood pressure. In some cases, post-reperfusion syndrome can progress to a condition known as post-reperfusion vasoplegia which is a condition where severely low blood pressure persists even after blood flow is restored to the liver. This is often accompanied by complications such as improperly functioning kidneys, blood clotting disorders, and complications with the transplanted liver that can significantly affect patient outcomes. Recent studies have shown than inhaled nitric oxide (a gas that can relax blood vessels) can reduce the severity of IRI in the liver. This study is being conducted to determine whether the administration of inhaled nitric oxide during surgery reduces the severity of post-reperfusion syndrome and the incidence of post-reperfusion vasoplegia in adult patients undergoing liver transplantation. This is a before-and-after study design that will involve both the retrospective collection of data between the time period of January 1, 2020 - May 31, 2025 and prospective interventions involving adult liver transplant recipients.

Conditions

Liver Diseases; Reperfusion Injury; Vasoplegia

Keywords

Inhaled Nitric Oxide; Anesthesia

Outcome Measures

Primary Outcomes (2)

• Impact of nitric oxide to reduce the severity of post-reperfusion syndrome in adult patients undergoing liver transplantation

  This will be measured by considering the following parameters for these indications following iNO administration: • Incidence of post-reperfusion syndrome, defined as a ≥30% drop in mean arterial pressure within 5 minutes of reperfusion, lasting for more than 1 minute

  0-72 hours following liver transplant

• Impact of nitric oxide to reduce the incidence of incidence of post-reperfusion vasoplegia in adult patients undergoing liver transplantation

  This will be measured by considering the following parameters for these indications following iNO administration: • Incidence of vasoplegia, defined as persistent hypotension requiring norepinephrine ≥ 0.1 µg/kg/min for ≥ 30 minutes despite adequate volume resuscitation

  0-72 hours following liver transplant

Secondary Outcomes (6)

• Impact of intraoperative administration of inhaled nitric oxide (iNO) on patient hospital stay.

  0-72 hours following liver transplant

• Impact of intraoperative administration of inhaled nitric oxide (iNO) on in-hospital mortality

  0-72 hours following liver transplant

• Impact of intraoperative administration of inhaled nitric oxide (iNO) on liver function

  0-72 hours following liver transplant

• Impact of intraoperative administration of inhaled nitric oxide (iNO) on blood clotting

  0-72 hours following liver transplant

• Impact of intraoperative administration of inhaled nitric oxide (iNO) on early graft dysfunction

  0-72 hours following liver transplant

Study Arms (2)

No Intervention Retrospective "Before" Group

ACTIVE COMPARATOR

Adult liver transplant recipients identified retrospectively from the institutional transplant database, including all patients who underwent orthotopic liver transplantation since the implementation of the OneChart electronic medical record (EMR) system between the time period of January 1, 2020 - May 31, 2025.

Other: No Intervention Retrospective "Before" Group

Prospective iNO Administration ("After" Group)

EXPERIMENTAL

Adult patients undergoing liver transplantation with prospective intervention involving intraoperative administration of inhaled nitric oxide (iNO) and prospective data collection.

Drug: Prospective iNO Administration ("After" Group)

Interventions

Prospective iNO Administration ("After" Group) DRUG

Adult patients undergoing liver transplantation after the implementation of the iNO protocol, with prospective intervention involving intraoperative administration of iNO and prospective data collection. Inhaled nitric oxide will be administered via the anesthesia machine, under the supervision of the attending Anesthesiologist, at a concentration of 20 parts per million (ppm) starting at induction of anesthesia. At the onset of the anhepatic phase (i.e., after explantation of the native liver), the concentration will be increased to 80 ppm. Administration will be continued until the end of the surgical procedure, at which point iNO will be discontinued.

Prospective iNO Administration ("After" Group)

No Intervention Retrospective "Before" Group OTHER

Adult liver transplant recipients identified retrospectively from the institutional transplant database, including all patients who underwent orthotopic liver transplantation since the implementation of the OneChart electronic medical record (EMR) system between the time period of January 1, 2020 - May 31, 2025.

No Intervention Retrospective "Before" Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (age ≥ 18 years)
• Undergoing or underwent (for the retrospective "before" group) primary orthotopic liver transplantation. Retrospective data collection for retrospective group will take place between January 1, 2020 - May 31, 2025.
• Written informed consent obtained for patients in the prospective ("after") group

You may not qualify if:

• History of pulmonary arterial hypertension (mean pulmonary artery pressure ≥ 25 mmHg)
• Re-transplantation
• Acute fulminant hepatitis
• Combined organ transplantation (e.g., liver-kidney)
• Lack of complete data for propensity matching - Inability to communicate in the English language

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Related Publications (7)

• Lang JD Jr, Smith AB, Brandon A, Bradley KM, Liu Y, Li W, Crowe DR, Jhala NC, Cross RC, Frenette L, Martay K, Vater YL, Vitin AA, Dembo GA, Dubay DA, Bynon JS, Szychowski JM, Reyes JD, Halldorson JB, Rayhill SC, Dick AA, Bakthavatsalam R, Brandenberger J, Broeckel-Elrod JA, Sissons-Ross L, Jordan T, Chen LY, Siriussawakul A, Eckhoff DE, Patel RP. A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation. PLoS One. 2014 Feb 12;9(2):e86053. doi: 10.1371/journal.pone.0086053. eCollection 2014.

  PMID: 24533048 BACKGROUND

• Lang JD Jr, Teng X, Chumley P, Crawford JH, Isbell TS, Chacko BK, Liu Y, Jhala N, Crowe DR, Smith AB, Cross RC, Frenette L, Kelley EE, Wilhite DW, Hall CR, Page GP, Fallon MB, Bynon JS, Eckhoff DE, Patel RP. Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest. 2007 Sep;117(9):2583-91. doi: 10.1172/JCI31892.

  PMID: 17717604 BACKGROUND

• Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury. J Gastroenterol Hepatol. 2000 Jul;15(7):718-24. doi: 10.1046/j.1440-1746.2000.02207.x.

  PMID: 10937675 BACKGROUND

• Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651-5. doi: 10.1073/pnas.88.11.4651.

  PMID: 1675786 BACKGROUND

• Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005 Feb;115(2):209-18. doi: 10.1172/JCI24282.

  PMID: 15690074 BACKGROUND

• Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ. Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest. 2005 May;115(5):1232-40. doi: 10.1172/JCI22493. Epub 2005 Apr 14.

  PMID: 15841216 BACKGROUND

• Cannon RO 3rd. Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clin Chem. 1998 Aug;44(8 Pt 2):1809-19.

  PMID: 9702990 BACKGROUND

MeSH Terms

Conditions

Liver Diseases; Reperfusion Injury; Vasoplegia

Condition Hierarchy (Ancestors)

Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Raffael Zamper

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raffael Zamper

CONTACT

5196858500; Raffael.PereiraCezarZamper@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anesthesiologist, Assistant Professor

Study Record Dates

• First Submitted: August 7, 2025
• First Posted: August 15, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share