Ischemia Reperfusion InjuryNCT00796588
The Effect of Remote Ischemic Preconditioning in Patients Undergoing Major Liver Surgery
A study testing remote preconditioning in people with Ischemia Reperfusion Injury, run by Royal Free Hampstead NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Ischemia Reperfusion Injury
- What is being tested?
- remote preconditioning
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2005to Dec 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients above the age of 18 undergoing liver surgery
Who cannot join
- 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
Show all 10Show fewer
- HIV infection
- Fulminant sepsis
- Severe comorbid disease
- Patients below the age of 18
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Ischemia Reperfusion Injury
- Being tested
- remote preconditioning
- Keywords
- preconditioning, remote
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
remote preconditioningOther
Also called RIPC
Three periods of 10 minute occlusion of blood supply to leg using a pneumatic tourniquet
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | Patients undergoing liver surgery without the designated intervention Receives: Other: remote preconditioning |
| RIPC | Other | application of pneumatic tourniquet in patients undergoing liver surgery Receives: Other: remote preconditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Does RIPC reduce ischemia reperfusion injury in patients undergoing liver surgery
Measured: 8 years
Secondary outcomes (1)
Changes in liver regeneration
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2008 (estimated)
- Study startApr 2005
- Primary completionDec 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemia Reperfusion InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Free Hampstead NHS Trust
- Sponsor type
- University, hospital or other
- Investigators
- Brian R Davidson, FRCS, MD, Principal investigator, Royal Free Hospital and medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00796588
- Sponsor's protocol ID
- RFH:6100
- Status last verified
- Nov 2008
- First submitted
- 21 Nov 2008
- Last updated
- 24 Nov 2008
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 18456674Robertson 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.
PubMed 27054029
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Remote Ischemic Preconditioning in Patients Undergoing Major Liver Surgery
- ClinicalTrials.gov ID
- NCT00796588
- Acronym / sponsor ID
- RFH:6100
- Conditions
- Ischemia Reperfusion Injury
- Keywords
- preconditioning, remote
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Royal Free Hampstead NHS TrustUniversity, hospital or other
- Study start
- Apr 2005
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 24 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | Other: remote preconditioningPatients undergoing liver surgery without the designated intervention |
| RIPC | Other | Other: remote preconditioningapplication of pneumatic tourniquet in patients undergoing liver surgery |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients above the age of 18 undergoing liver surgery
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| remote preconditioningAlso: RIPCThree periods of 10 minute occlusion of blood supply to leg using a pneumatic tourniquet | Other | Control group, RIPC |
Primary outcome
Does RIPC reduce ischemia reperfusion injury in patients undergoing liver surgery
Time frame: 8 years
1 secondary outcome
Changes in liver regeneration
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2008.
- Background: PubMed 18456674Hausenloy 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.
- Derived from this study: PubMed 27054029Robertson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian R Davidson, FRCS, MD principal investigator
Royal Free Hospital and medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing remote preconditioning in people with Ischemia Reperfusion Injury, run by Royal Free Hampstead NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Nov 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Does RIPC reduce ischemia reperfusion injury in patients undergoing liver surgery (time frame: 8 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00796588, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2008.