None listed
Conditions
Brief summary
Liver transplantation is the only curative treatment option for patients with advanced liver disease. It is a prolonged and highly complex operation, during which many patients require medication to maintain their blood pressure at a safe level. Complications following this invasive (but life-saving) surgery are common. For example, approximately four in ten patients experience reduced kidney function, which can impact quality of life and life-expectancy. Many previous studies have sought to identify the risk factors for impaired kidney function following liver transplantation. There is evidence that both low blood pressure as well as the medication commonly used to raise blood pressure (noradrenaline) may increase the risk of kidney problems. However, a relatively novel medication, known as ‘angiotensin-II’ may offer a more kidney-friendly alternative, improving blood pressure with less risk of harming the kidneys. Our study will compare angiotensin-II to noradrenaline as a blood pressure support medication during liver transplantation. It is a small ‘pilot’ or ‘test’ study, with the aim of assessing the feasibility of a future larger trial. Our primary goal is to explore different assessments of study practicality, which will inform the running of the future study. In addition, we will compare various side-effects and safety outcomes between the two drugs, including the occurrence of kidney impairment, among others.
Interventions
This is an open-label, parallel-group, randomised controlled feasibility trial comparing angiotensin-II to noradrenaline as a primary vasopressor in liver transplant recipients. Eligible patients undergoing liver transplantation will be randomised to either the intervention arm (Angiotensin-II) or the control arm (Noradrenaline) in a 1:1 ratio.
Angiotensin-II will be prepared at a concentration of 5000ng/ml (2.5 mg angiotensin-II in 500ml of normal saline). The rate of intravenous administrat
This is an open-label, parallel-group, randomised controlled feasibility trial comparing angiotensin-II to noradrenaline as a primary vasopressor in liver transplant recipients. Eligible patients undergoing liver transplantation will be randomised to either the intervention arm (Angiotensin-II) or the control arm (Noradrenaline) in a 1:1 ratio. Angiotensin-II will be prepared at a concentration of 5000ng/ml (2.5 mg angiotensin-II in 500ml of normal saline). The rate of intravenous administration will be titrated to achieve a target MAP between 60-90 mmHg, with a dose range equivalent to 0 to 40 ng/kg/min. The allocated study drug (either Angiotensin-II or Noradrenaline) will be administered as needed (titrated based on MAP) from the time that central venous access is established (in the operating theatre) until the early post-operative period (for a maximum of 48 hours in ICU). The drug will be administered by the treating anaesthetist within the operating theatre, and subsequently by the intensive care unit nursing staff, under the guidance of the treating intensivist within the ICU.
Sponsors
Austin Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (greater than or equal to 18 years) * Listed for isolated liver transplantation
Exclusion criteria
Surgical Factors: * Concurrent multi-visceral transplantation * Planned use of intra-operative veno-venous bypass Patient Factors: * Known allergy to angiotensin-II, noradrenaline or any excipients used in their formulation (e.g., mannitol or sodium metabisulphite respectively) * Extremes of body weight (TBW less than 50 kg OR TBW greater than or equal to 140 kg) * Fulminant liver failure * Pre-operative vasopressor requirement (including terlipressin) * Pre-existing end-stage kidney disease, defined as baseline estimated glomerular filtration rate (eGFR) < 15ml/min/1.73m2 OR pre-operative requirement for renal replacement therapy (peritoneal or haemodialysis within previous month) * History of splanchnic venous thrombosis (e.g., Budd-Chiari syndrome, portal venous thrombosis, mesenteric vein thrombosis) ever * History of other venous thrombosis (deep vein thrombosis, pulmonary embolism) or arterial thrombosis (myocardial infarction, ischaemic stroke, mesenteric ischaemia) within the preceding 6 months * Therapeutic anticoagulation (e.g., DOACs) for any medical indication not otherwise outlined above * Inherited hypercoagulability disorders (e.g., Factor V Leiden) * Vasospastic diseases (e.g., Raynaud’s disease or acrocyanosis) * Severe left ventricle (LV) systolic impairment (LVEF < 30%) * Unrepaired aortic aneurysm or dissection * Pregnant or breast-feeding women * Patients lacking capacity, or inadequate language comprehension for informed consent * Patients previously included in the study (i.e., previous LTx during recruitment period) Logistic Factors: * Non-availability of raw haemodynamic data (i.e., surgical case proceeding outside of the usual liver transplant theatre)
Outcome results
None listed