Liver Transplantation, Renal Failure
Conditions
Brief summary
The purpose of the study is to determine whether an octreotide infusion during liver transplantation improves renal outcomes, intraoperative blood pressure and reduces haemorrhage and transfusion requirement.
Detailed description
Common and serious complications of liver transplantation surgery include renal failure, haemorrhage and blood transfusion. These complications prolong post-operative recovery, increase the risk of liver graft failure, mortality and the need for long-term renal dialysis. The drug octreotide is a synthetic analogue of somatostatin with comparable physiological effects and a good side-effect profile. Existing evidence in liver transplantation supports octreotide efficacy in improving renal function, reducing bleeding and enhancing blood pressure. However, there is no robust randomised controlled trial evidence for octreotide in liver transplantation and limited safety data regarding its use in this setting. This is a multi centre, prospective double-blind, randomised, placebo-controlled trial of octreotide infusion during liver transplantation. The patients will be randomised in a 2:1 ratio to either octreotide or placebo groups. Stratified randomisation of patients is by donation type (DCD vs. DBD). Patients will be randomised in the anaesthetic room and study medication given as an initial bolus of 5ml (100mcg octreotide or saline) prior to surgical incision and then continued throughout surgery at 5ml/hr (100mcg/hour octreotide or saline).
Interventions
DRUGOctreotide Acetate
Octreotide syringes will contain 50ml of octreotide acetate at 20mcg/ml in 0.9% w/v sodium chloride in water.
OTHERPlacebo
Sodium chloride 0.9% w/v
Sponsors
National Institute for Health Research, United Kingdom
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinding (masking) will be achieved through the use of identical active drug product and control study drug syringes that are allocated by centrally-controlled and administered randomisation such that no clinical, research or statistical support staff are aware of allocation.
Intervention model description
Patients will be randomised in a 2:1 ratio to either octreotide or placebo groups. Stratified randomisation of patients by source of liver graft (brain death or cardiac death) will be performed.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged 18 years and over undergoing primary liver transplantation of a whole or partial liver graft from a cardiac or brain dead donor. * Provision of written informed consent.
Exclusion criteria
* Previous solid organ transplant. * Acute liver failure. * Fulminant hepatic failure. * Patients receiving a living donor liver graft. * Patients currently admitted to ICU prior to transplantation. * Requirement of haemodialysis or CVVHF pre-operatively. * Known allergy or adverse reaction to octreotide. * Pre-operative decision to use intra-operative CVVHF. * A positive pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ability to recruit patients. | Approximately 180 days. | This will be assessed by: • Ability to recruit patients (target: ≥ 30% consent rate of eligible patients admitted for transplant) |
| Completion of the study intervention. | Approximately 9.5 hours. | This will be assessed by: • The percentage of patients successfully completing the study intervention. Defined as eligible patients who receive the entire study drug infusion in a blinded manner. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of new chronic kidney disease or deterioration of chronic kidney disease. | At thirty and ninety days post operative. | This is defined as a new persistent estimated glomerular filtration rate below 60 ml/min/1.73m2 or a decline in pre-existing glomular function to a more severe KDIGO chronic kidney disease. status. |
| Incidence of early allograft dysfunction. | At day seven post-operatively | Early allograft dysfunction defined by the presence of one or more of the following: total bilirubin ≥ 10 mg/dL (171 μmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST \> 2,000 IU/L within the first 7 days post-operatively. |
| Patient mortality. | At thirty and ninety days post-operatively. | Patient mortality at thirty and ninety days post-operatively. |
| Intra-operative red blood cell salvage. | Within 24, 72 and 168 hours post-operatively. | Total volume of intra-operative red blood cell salvage available for reinfusion following washing and centrifugation. |
| The incidence of acute kidney injury. | Within 24, 72 and 168 hours post-operatively. | This will be defined by Acute Kidney Injury Network stage 1 criteria (a 50% increase in serum creatinine from baseline or less than 0.5 ml/kg/hr urine output for 6-12 hours post-transplant). |
| Incidence of adverse events secondary to study drug infusion. | Intra-operatively and up to 24 hours post-operatively. | Recorded adverse events are: abnormal QTc interval (460ms in men, 470ms in women) or associated ventricular arrhythmia or Torsades de Pointes, unexpected or resistant hypoglycaemia (blood sugar \< 4mM) and clinical suspicion of allergic or anaphylactic reaction. |
| PROMs_ data collection_1 | For EuroQoL-5D-5, At Day 1 and at thirty and ninety days post-operatively. Then at 3, 6 & 9 months. | PROMs (Patient Recorded Outcome Measures) of quality of life . The questionnaires to be used to quantify quality of life is EuroQoL-5D-5L. |
| PROMs_ data collection_2 | For LDQOL, At Day 1 and at thirty and ninety days post-operatively. Then at 3, 6 & 9 months. | PROMs (Patient Recorded Outcome Measures) of quality of life . The questionnaires to be used to quantify quality of life is LDQOL. |
| Volume of packed red blood cell transfusion. | Intra-operatively and at 24, 72 and 168 hours post-operatively. | Volume of packed red blood cell transfusion administered intra-operatively and at 24, 72 and 168 hours post-operatively. |
| Post-operative incidence of a new requirement for renal replacement therapy. | Within 24 hours, 72 hours, one and two weeks post-operatively. | Administration of haemofiltration or haemodiafiltration. |
Countries
United Kingdom
Outcome results
None listed