The Effect of Remote Ischemic Preconditioning in Patients Undergoing Major Liver Surgery

Tracking Information
First Submitted Date ICMJE	November 21, 2008
First Posted Date ICMJE	November 24, 2008
Last Update Posted Date	November 24, 2008
Study Start Date ICMJE	April 2005
Estimated Primary Completion Date	December 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 21, 2008)	Does RIPC reduce ischemia reperfusion injury in patients undergoing liver surgery [ Time Frame: 8 years ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	No Changes Posted
Current Secondary Outcome Measures ICMJE; (submitted: November 21, 2008)	Changes in liver regeneration [ Time Frame: 1 year ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	The Effect of Remote Ischemic Preconditioning in Patients Undergoing Major Liver Surgery
Official Title ICMJE	The Effect of Remote Ischemic Preconditioning in Patients Undergoing Major Liver Surgery
Brief Summary	The project has been designed to determine whether a brief period of leg ischemia will reduce the I/R injury sustained by the liver during liver surgery and liver transplantation. Adult patients (aged above 18) for liver resection (LR group) and for orthotopic liver transplantation (OLT group) will be analysed separately. Patients from each category will be randomised to two groups - a control and a Remote IPC group. In the remote IPC group Ischemic preconditioning will be induced during surgery by applying a pneumatic tourniquet to the upper part of the right thigh and then inflating it to twice the measured systolic arterial pressure in order to occlude the blood supply of the leg for 10 minutes. The tourniquet will then be deflated for 10 minutes to reperfuse the leg. This is repeated thrice to precondition the skeletal muscles of the leg.
Detailed Description	Data Collection & Measurements: Blood Measurements: Blood will be collected at seven different time points, Baseline, Post IPC, 15 and 90 minutes post IRI and then 6,12 and 24 hours post IRI. At each time point approximately 35 ml of blood will be collected. Samples will be collected for the following measurements: Serum LFT and electrolytes, Serum CPK isozymes, Plasma cytokines, coagulation profile, TEG profile, Plasma cytokines, xanthine and XO/XDH activities, Plasma neutrophil activation, Total plasma Nitrate levels, Plasma lactate and ammonia levels and pulmonary artery blood (from indwelling Swan Ganz) for Plasma Myeloperoxidase levels. Some of these are routine measurements done during and after liver surgery. Biopsies: Two Liver trucut biopsies - one prior to implantation (and in case of liver resection from the normal remnant liver before occlusion) and the other immediately prior to closure of the abdomen - will be taken to study the changes in tissue oxidation, tissue adhesion molecule upregulation and morphology prior to and after preconditioning. Intra-operative haemodynamcis: Cardio-pulmonary haemodynamics will be monitored using a Swan-Ganz catheter (if it is clinically indicated and already in place) to note the effects of skeletal muscle ischemic preconditioning on the liver, lungs and the heart. In those patients undergoing liver resection invasive heaemodynamic monitoring will not be performed for the purpose of the study, if not required clinically by the anaesthetists and intensive care physicians. Non-invasive measurements will be made of hepatic and cutaneous circulation using surface Laser Doppler flow meter and Ultra sound probes. Cutaneous microvascular responses to iontophoresis (non-invasive) of acetylcholine, an endothelium-independent vasodilator and sodium nitroprusside, and endothelium-independent vasodilator will be measured using the laser Doppler flow meter. NIRS probes (non -invasive) will be used on the surface of the to measure liver tissue oxygenation. All probes will be properly sterilised prior to application. Post-operative heamodynamics: Cardio-pulmonary haemodynamics will continue to be monitored using a Swan-Ganz catheter (routinely inserted during liver transplantation) in the post-operative period for 24 hours. ICG measurements: To assess liver function by injecting 0.5 mg/kg of indocyanine green (ICG) pre-operatively, intra-operatively and post operatively. ICG is routinely used in many liver centres for the assessment of liver function in clinical practise. No additional blood samples will be collected since the uptake and excretion of ICG by the liver will be measured by a non invasive digital pulse densitometric device (ICG Pulsion) connected to the patient by a finger sensor.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Participant); Primary Purpose: Health Services Research
Condition ICMJE	Ischemia Reperfusion Injury
Intervention ICMJE	Other: remote preconditioning; Three periods of 10 minute occlusion of blood supply to leg using a pneumatic tourniquet; Other Name: RIPC
Study Arms	No Intervention: Control group Patients undergoing liver surgery without the designated intervention Intervention: Other: remote preconditioning; RIPC application of pneumatic tourniquet in patients undergoing liver surgery Intervention: Other: remote preconditioning
Publications *	Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2. Review.; Robertson FP, Goswami R, Wright GP, Fuller B, Davidson BR. Protocol for a prospective randomized controlled trial of recipient remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial). Transplant Res. 2016 Apr 6;5:4. doi: 10.1186/s13737-016-0033-4. eCollection 2016.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: November 21, 2008)	48
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	December 2012
Estimated Primary Completion Date	December 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patients above the age of 18 undergoing liver surgery Exclusion Criteria: Absence of written, informed consent.; Patients with symptomatic peripheral vascular disease and absent or weak peripheral pulses.; Patients with varicose veins and venous ulcers; Patients with blood disorders, eg. sickle cell disease; Patients with any localised limb infections eg. cellulitis; Pregnancy; HIV infection; Fulminant sepsis; Severe comorbid disease; Patients below the age of 18
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 90 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United Kingdom
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00796588
Other Study ID Numbers ICMJE	RFH:6100
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Prof Brian R. Davidson, Royal Free Hospital and Medical School
Study Sponsor ICMJE	Royal Free Hampstead NHS Trust
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Brian R Davidson, FRCS, MD Royal Free Hospital and medical School
PRS Account	Royal Free Hampstead NHS Trust
Verification Date	November 2008
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP