A Feasibility Study of Octreotide Infusion During Liver Transplant. (Octreotide)

A Double-blind Randomised Placebo-controlled Feasibility Study to Assess the Impact of Octreotide Infusion During Liver Transplantation on Post-operative Renal Failure.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Transplantation; Renal Failure
• Intervention / Treatment: Drug: Octreotide Acetate; Other: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • University Hospital Birmingham
  • London, United Kingdom
    • Royal Free Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention group; Octreotide intravenous infusion, 100mcg bolus with a subsequent infusion of 100mcg per hour during surgery.	Drug: Octreotide Acetate; Octreotide syringes will contain 50ml of octreotide acetate at 20mcg/ml in 0.9% w/v sodium chloride in water.
Placebo Comparator: Placebo group; Sodium chloride 0.9% w/v	Other: Placebo; Sodium chloride 0.9% w/v

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to recruit patients.	This will be assessed by: • Ability to recruit patients (target: ≥ 30% consent rate of eligible patients admitted for transplant)	Approximately 180 days.
Completion of the study intervention.	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.	Approximately 9.5 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of acute kidney injury.	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).	Within 24, 72 and 168 hours post-operatively.
Post-operative incidence of a new requirement for renal replacement therapy.	Administration of haemofiltration or haemodiafiltration.	Within 24 hours, 72 hours, one and two weeks post-operatively.
Incidence of new chronic kidney disease or deterioration of chronic kidney disease.	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.	At thirty and ninety days post operative.
Incidence of early allograft dysfunction.	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.	At day seven post-operatively
Patient mortality.	Patient mortality at thirty and ninety days post-operatively.	At thirty and ninety days post-operatively.
Intra-operative red blood cell salvage.	Total volume of intra-operative red blood cell salvage available for reinfusion following washing and centrifugation.	Within 24, 72 and 168 hours post-operatively.
Volume of packed red blood cell transfusion.	Volume of packed red blood cell transfusion administered intra-operatively and at 24, 72 and 168 hours post-operatively.	Intra-operatively and at 24, 72 and 168 hours post-operatively.
Incidence of adverse events secondary to study drug infusion.	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.	Intra-operatively and up to 24 hours post-operatively.
PROMs_ data collection_1	PROMs (Patient Recorded Outcome Measures) of quality of life . The questionnaires to be used to quantify quality of life is EuroQoL-5D-5L.	For EuroQoL-5D-5, At Day 1 and at thirty and ninety days post-operatively. Then at 3, 6 & 9 months.
PROMs_ data collection_2	PROMs (Patient Recorded Outcome Measures) of quality of life . The questionnaires to be used to quantify quality of life is LDQOL.	For LDQOL, At Day 1 and at thirty and ninety days post-operatively. Then at 3, 6 & 9 months.

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: National Institute for Health Research, United Kingdom

Publications and helpful links

General Publications

• Fabes J, Ambler G, Shah B, Williams NR, Martin D, Davidson BR, Spiro M. Protocol for a prospective double-blind, randomised, placebo-controlled feasibility trial of octreotide infusion during liver transplantation. BMJ Open. 2021 Dec 2;11(12):e055864. doi: 10.1136/bmjopen-2021-055864.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): January 31, 2024

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: 17/0508; PB-PG-0817-20023 (Other Grant/Funding Number: NIHR Research for Patient Benefit)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a plan to provide baseline and outcome data, including PROMs and treatment allocation.
• IPD Sharing Time Frame: Commencement only after publication of this trial and any subsequent substantive trial.
• IPD Sharing Access Criteria: We would only provide IPD on specific application for that data as part of meta-analysis or other comparable research, rather than providing an 'open book' approach. Eligible requests will come from genuine non-commercial research institutes with a plan to publish meta-analytical or systematic review outcomes. Requests will be reviewed by the TMG with discussion with the TSC as needed. Data will be provided in a basic spreadsheet database via institutional email, ensuring no PID is contained.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No