An interventional study of Prospective iNO Administration ("After" Group) and No Intervention Retrospective "Before" Group in Liver Diseases, Reperfusion Injury and Vasoplegia, sponsored by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-15.
Sponsored by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's · Not applicable, Interventional, and Treatment
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.
Orthotopic liver transplantation remains the only curative option for patients with end-stage liver disease. Despite continuous advances in surgical techniques and perioperative management, ischemia-reperfusion injury (IRI) remains a major contributor to early graft dysfunction, with clinical consequences including prolonged intensive care stay, increased morbidity, and higher resource utilization. Reperfusion of the donor liver, particularly after portal and arterial unclamping, frequently triggers a hemodynamic instability known as post-reperfusion syndrome. This syndrome is characterized by profound vasodilation, hypotension, and a significant increase in vasopressor requirements. In some patients, it progresses into post-reperfusion vasoplegia, a state of sustained low systemic vascular resistance and poor end-organ perfusion. This condition is often accompanied by renal dysfunction, coagulopathy, and impaired early graft function, which significantly affect patient outcomes.
The pathophysiology of hepatic IRI is complex, involving endothelial activation, neutrophil recruitment, oxidative stress, mitochondrial dysfunction, and cytokine release. A key mechanistic factor contributing to reperfusion injury is the reduced bioavailability of nitric oxide (NO), due either to decreased production by endothelial nitric oxide synthase (eNOS) or its rapid inactivation by reactive oxygen species and heme-containing proteins. NO plays an essential role in maintaining microvascular tone, limiting leukocyte adhesion, and protecting against mitochondrial and endothelial injury. Restoration of NO signaling has been shown to protect against IRI in preclinical models. Inhaled nitric oxide (iNO) is approved for pulmonary hypertension and neonatal hypoxemia, but accumulating evidence suggests that it may also exert extrapulmonary effects. Studies in both animals and humans have demonstrated that iNO can attenuate IRI in the liver, heart, and skeletal muscle by increasing circulating nitrite and other bioactive NO metabolites that act as reservoirs and mediators of NO activity during ischemic stress.
In the context of liver transplantation, two retrospective clinical studies have shown that intraoperative iNO administration (at 80 ppm (parts per million)) is safe and may accelerate the recovery of liver function, reduce hepatocellular apoptosis, and decrease postoperative complications. These findings suggest that iNO could modulate the hemodynamic response to reperfusion and improve graft performance. However, despite these promising results, no prospective controlled trials or before-after studies have yet evaluated the real-time impact of intraoperative iNO on reperfusion syndrome and vasoplegia in liver transplantation.
The investigators hypothesize that the intraoperative administration of inhaled nitric oxide reduces the severity of reperfusion syndrome and the incidence of post-reperfusion vasoplegia in adult patients undergoing liver transplantation. Furthermore, the investigators propose that this intervention contributes to improved early graft function, particularly with regard to excretory performance. The present study aims to prospectively assess these outcomes using a before-after design, comparing matched cohorts of patients undergoing liver transplantation with and without intraoperative iNO. By addressing this existing gap in the literature, the investigators hope to generate clinically relevant data that may support the integration of iNO into standard perioperative protocols for liver transplant recipients.
This study involves 2 patient groups:
For the prospective, "after" study group, the participant's liver transplant procedure will proceed according to plan. Informed, written consent will be obtained prior to the start of surgery.
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. Standard anesthesia and transplant protocols will be followed in both groups, with no additional changes aside from the administration of iNO.
Participation in the "before" group will only involve retrospective data collection from the patients' electronic medical record that will gather data collected during the period of January 1, 2020 - May 31, 2025.
Data that will be collected include demographic data, medical history, intraoperative surgical details, details of iNO administration (where applicable), and post-operative outcomes. The timeline for collecting postoperative outcomes will be between 0-72 hours following surgery.
824 studies on the registry are indexed under Liver Diseases; 152 are open to participants now.
This study's planned enrollment of 260 is above the median of 52 across 521 interventional studies indexed under Liver Diseases.
Browse Liver Diseases studies →London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's is the lead sponsor of 331 studies on the registry; 137 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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)
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.
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.
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
Time frame: 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
Time frame: 0-72 hours following liver transplant
Impact of intraoperative administration of inhaled nitric oxide (iNO) on patient hospital stay.
This will be measured by evaluating: • Length of ICU and hospital stay (measured in days).
Time frame: 0-72 hours following liver transplant
Impact of intraoperative administration of inhaled nitric oxide (iNO) on in-hospital mortality
This will be measured by evaluating: -In-hospital mortality
Time frame: 0-72 hours following liver transplant
Impact of intraoperative administration of inhaled nitric oxide (iNO) on liver function
This will be measured by evaluating: \- Peak serum ALT (Alanine Aminotransferase) and AST (Aspartate Aminotransferase) levels (measured in international units per litre (U/L)
Time frame: 0-72 hours following liver transplant
Impact of intraoperative administration of inhaled nitric oxide (iNO) on blood clotting
This will be measured by evaluating the following: \- Time to INR (International Normalized Ratio) normalization
Time frame: 0-72 hours following liver transplant
Impact of intraoperative administration of inhaled nitric oxide (iNO) on early graft dysfunction
This will be measured by the Olthoff criteria
Time frame: 0-72 hours following liver transplant
Impact of intraoperative administration of inhaled nitric oxide (iNO) on the requirements for post-operative therapies and medications.
This will be measured by recording the need for patients to receive the following after surgery: * Postoperative vasopressor requirement * Renal replacement therapy
Time frame: 0-72 hours following liver transplant
No study locations are listed for this record.
Plan to share: No
Start is estimated for Sep 2025; primary completion for Dec 2026, 15 months later.
Of 122 non-industry interventional studies with no phase under Liver Diseases, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 50. This study's planned 15 months is below that.
Counting every sponsor, half of 135 studies reached it within 24 months; a quarter within 12 and three quarters within 47.
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This study is not yet recruiting, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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