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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Royal Free Hampstead NHS Trust
ClinicalTrials.gov Identifier:
NCT00796588
First received: November 21, 2008
Last updated: NA
Last verified: November 2008
History: No changes posted
  Purpose

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.


Condition Intervention
Ischemia Reperfusion Injury
Other: remote preconditioning

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Health Services Research
Official Title: The Effect of Remote Ischemic Preconditioning in Patients Undergoing Major Liver Surgery

Further study details as provided by Royal Free Hampstead NHS Trust:

Primary Outcome Measures:
  • Does RIPC reduce ischemia reperfusion injury in patients undergoing liver surgery [ Time Frame: 8 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in liver regeneration [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: April 2005
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control group
Patients undergoing liver surgery without the designated intervention
Other: remote preconditioning
Three periods of 10 minute occlusion of blood supply to leg using a pneumatic tourniquet
Other Name: RIPC
RIPC
application of pneumatic tourniquet in patients undergoing liver surgery
Other: remote preconditioning
Three periods of 10 minute occlusion of blood supply to leg using a pneumatic tourniquet
Other Name: RIPC

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00796588

Locations
United Kingdom
Royal Free Hospital
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Royal Free Hampstead NHS Trust
Investigators
Principal Investigator: Brian R Davidson, FRCS, MD Royal Free Hospital and medical School
  More Information

Publications:
Responsible Party: Prof Brian R. Davidson, Royal Free Hospital and Medical School
ClinicalTrials.gov Identifier: NCT00796588     History of Changes
Other Study ID Numbers: RFH:6100
Study First Received: November 21, 2008
Last Updated: November 21, 2008
Health Authority: United Kingdom: Department of Health

Keywords provided by Royal Free Hampstead NHS Trust:
preconditioning
remote

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications

ClinicalTrials.gov processed this record on August 28, 2014