CTRI Number |
CTRI/2013/10/004072 [Registered on: 17/10/2013] Trial Registered Retrospectively |
Last Modified On: |
07/10/2013 |
Post Graduate Thesis |
No |
Type of Trial |
Interventional |
Type of Study
|
Drug |
Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
|
Better Outcomes in Living donor liver transplantation with Terlipressin |
Scientific Title of Study
|
Double-blind Randomized controlled trial of the peri-operative use of terlipressin in adult living donor liver transplantation. |
Trial Acronym |
BOLT (Better Outcomes with Terlipressin in Living donor liver transplantation) |
Secondary IDs if Any
|
Secondary ID |
Identifier |
NIL |
NIL |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
Name |
Mettu Srinivas Reddy |
Designation |
Senior Consultant Surgeon |
Affiliation |
Global Hospital and Health City |
Address |
Institute of Liver Diseases and Transplantation
Global Hospital and Health City
Perumbakkam,
Chennai, India
Chennai TAMIL NADU 600100 India |
Phone |
9840054648 |
Fax |
|
Email |
smettu.reddy@gmail.com |
|
Details of Contact Person Scientific Query
|
Name |
Mettu Srinivas Reddy |
Designation |
Senior Consultant Surgeon |
Affiliation |
Global Hospital and Health City |
Address |
Institute of Liver Diseases and Transplantation
Global Hospital and Health City
Perumbakkam,
Chennai, India
Kancheepuram TAMIL NADU 600100 India |
Phone |
9840054648 |
Fax |
|
Email |
smettu.reddy@gmail.com |
|
Details of Contact Person Public Query
|
Name |
Mettu Srinivas Reddy |
Designation |
Senior Consultant Surgeon |
Affiliation |
Global Hospital and Health City |
Address |
Institute of Liver Diseases and Transplantation
Global Hospital and Health City
Perumbakkam,
Chennai, India
Kancheepuram TAMIL NADU 600100 India |
Phone |
9840054648 |
Fax |
|
Email |
smettu.reddy@gmail.com |
|
Source of Monetary or Material Support
|
Global Hospital and Health City, Chennai, India |
|
Primary Sponsor
|
Name |
Global Hospital health City |
Address |
Perumbakkam
Chennai 600100
INDIA |
Type of Sponsor |
Research institution and hospital |
|
Details of Secondary Sponsor
|
|
Countries of Recruitment
|
India |
Sites of Study
|
No of Sites = 1 |
Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
Dr M Srinivas Reddy |
Global Hospital and Health City |
Institute of Liver Surgery & Transplantation
Global Hospital and Health City
Perumbakkam
Chennai
INDIA 600100 Chennai TAMIL NADU |
9840054648
smettu.reddy@gmail.com |
|
Details of Ethics Committee
|
No of Ethics Committees= 1 |
Name of Committee |
Approval Status |
Institutional Ethics Committee, Global Hospital, Chennai, India |
Approved |
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
|
Health Type |
Condition |
Patients |
Adult End stage liver disease patients undergoing living donor liver transplantation, |
|
Intervention / Comparator Agent
|
Type |
Name |
Details |
Comparator Agent |
Normal saline |
Infusion rate calculated by recipient weight in kg divided by 10 rounded off to the nearest ml/hour |
Intervention |
Terlipressin |
Terlipressin infusion started during living donor liver transplantation and continued for 72 hours postoperatively. Initial bolus of 1mg over 30 minutes followed by 2microgram per kg per hour. Solution prepared by diluting 1mg Terlipressin (Ferring Inc) in 50 ml saline. |
|
Inclusion Criteria
|
Age From |
18.00 Year(s) |
Age To |
60.00 Year(s) |
Gender |
Both |
Details |
Adult patients undergoing first living donor liver transplantation for primary liver disease
GRWR<1.2
|
|
ExclusionCriteria |
Details |
Combined liver-kidney transplants
Significant pre-operative renal dysfunction (eGFR<50)
Significant uncorrected coronary artery disease
Urgent transplants
Re-transplants |
|
Method of Generating Random Sequence
|
Computer generated randomization |
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
Primary Outcome
|
Outcome |
TimePoints |
Portal pressure |
Before recipient hepatectomy
After arterial reperfusion |
|
Secondary Outcome
|
Outcome |
TimePoints |
Blood loss
Blood product requirement
Intraoperative urine output
Intraoperative lactate
Intraoperative inotropic requirement
Postoperative renal dysfunction
Postoperative complications
ICU stay
Hospital stay
Adverse effects of trial medication |
Intraoperative
Postoperative |
|
Target Sample Size
|
Total Sample Size="40" Sample Size from India="40"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
Phase of Trial
|
Phase 2/ Phase 3 |
Date of First Enrollment (India)
|
05/07/2012 |
Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
Date of First Enrollment (Global) |
Date Missing |
Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
Estimated Duration of Trial
|
Years="2" Months="0" Days="0" |
Recruitment Status of Trial (Global)
|
Not Applicable |
Recruitment Status of Trial (India) |
Open to Recruitment |
Publication Details
|
Nil |
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
|
Cirrhosis is associated with portal hypertension. Shift of blood to the splanchnic circulation with relative decrease of the systemic circulation volume is also well described. This manifests as increased bleeding secondary to portal hypertension during liver transplantation. Peri-operative renal dysfunction is also well described. Living donor liver transplantation involves transplanting a graft liver, which is half the normal liver size into the recipient. This exposes the graft to high portal blood flow termed ‘portal hyperperfusion’. While it resolves spontaneously in mild cases, it has the potential to cause prolonged graft dysfunction when the graft recipient weight ratio (GRWR) is less than 0.8. This is termed ‘small for size syndrome’. Terlipressin is a vasopressin analogue, which causes splanchnic vasoconstriction leading to a shift of blood from portal to systemic circulation. It is routinely used in management of variceal bleeding and hepato-renal syndrome in cirrhotic patients. Terlipressin can potentially improve outcome in LDLT by decreasing intra-operative haemorrhage, improving renal function and decreasing portal hyperperfusion. It has been reported to improve outcomes in LDLT in a few recent studies. However this area needs further investigation. The present study is planned as a double blind, randomised controlled trial comparing the use of terlipressin during the peri-transplant period with a placebo group. This study will enroll adults patients undergoing LDLT in our unit with GRWR lesser than 1.2. Subjects will be randomised to terlipressin group or placebo group. Terlipressin group will receive an initial bolus of terlipressin at start of transplant operation followed by continuous infusion for 72 hours post-operatively. Placebo group will receive saline infusion at the same rate loaded in similar looking syringes. The patient and the treating clinicians will be unaware of each patient’s allocation. The primary end-point is a drop in portal pressure after implantation. Secondary end-points of the trial include intra-operative haemo-dynamic parameters, intra-operative blood loss, transfusion requirements, post-operative liver function tests, renal function and morbidity. In addition, histological markers of tissue injury will be compared between the two groups. If significant improvement in post-transplant outcomes can be achieved by the use of peri-operative terlipressin, the latter can become the standard of care for all adult LDLT. |