Hepatocellular InjuryNCT01099475
Effect of Intermittent Pedicle Clamping on Hepatocellular Injury During Liver Surgery
A study testing Pringle manoeuvre 15 minutes and Pringle manoeuvre 30 minutes in people with Hepatocellular Injury and Blood Loss, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
In order to prevent excessive blood loss during liver surgery, an intermittent Pringle manoeuvre (IPM) can be applied. This implies a temporary clamping of the portal vein and hepatic artery in the hepatoduodenal ligament in order to occlude hepatic inflow. The optimal duration of the IPM is unknown. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Injury, Blood Loss
- What is being tested?
- Pringle manoeuvre 15 minutes and Pringle manoeuvre 30 minutes
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2007to Apr 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients > 18 years of age and < 100 years of age
- primary or secondary liver tumours requiring liver surgery
Who cannot join
- pre-existent liver disease (e.g. inflammatory liver disease, cirrhosis, inborn errors of metabolism)
- cholangiocarcinoma requiring biliary tract reconstruction during surgery
- steroid hormone medication
- tumours deemed irresectable during liver surgery
- laparoscopic liver surgery
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Centre
Maastricht, PO Box 5800, 6202 AZ
About this study
Official title: Randomized Controlled Trial on the Effect of Intermittent Pedicle Clamping Using 15 or 30 Minutes Ischemic Intervals During Liver Surgery
In order to prevent excessive blood loss during liver surgery, an intermittent Pringle manoeuvre (IPM) can be applied. This implies a temporary clamping of the portal vein and hepatic artery in the hepatoduodenal ligament in order to occlude hepatic inflow. The optimal duration of the IPM is unknown. This randomized controlled trial aimed to analyse differences in hepatocellular damage after 15 minutes or 30 minutes IPM during liver surgery for primary or secondary liver tumours.
Read the detailed description
Surgical procedure Patients were anaesthetized using isoflurane and propofol. They routinely had an epidural catheter, urinary catheter, two peripheral venous catheters and indwelling catheters in a jugular vein and radial artery. Body temperature was maintained using a Bair Hugger system (Arizant Healthcare Inc. Eden Prairie, Minnesota).
The surgical procedure was performed using a subcostal bilateral incision and Olivier retractors to improve exposure. After dissection of the teres hepatis ligament, the liver was mobilized. Thereafter, an intra-operative ultrasound was performed to define the position of the tumour in relation to vascular and biliary structures. As IPM was not routinely applied, a patient was randomized for 15 minted IPM (15IPM) or 30 minutes IPM (30IPM) only after the surgeon had decided a complete Pringle manoeuvre would be required. During 15IPM or 30IPM, the complete portal triad was clamped using a rubber sling. The time of inflow occlusion was adapted to the need according to the randomization protocol. Occasionally, the left or right pedicle was ligated after protocolled IPM. Five minutes reperfusion intervals were applied during which transection was stopped and cut surfaces were gently compressed to ensure hemostasis. A Cavitron Ultrasonic Surgical Aspirator (CUSA system 200 macrodissector, Cavitron Surgical Systems, Stamford, Connecticut) and Argon beam coagulation (Force GSU System, Valleylab, Boulder, Colorado) were used for liver transection. A stapler device or clamps were used for transection of the hepatic veins. Central venous pressure was maintained below 5 centimetre of water (cm H2O) during transection to reduce venous back-bleeding. After surgery, the weight of the resection specimen was recorded. Perioperative care was protocolled, as described earlier.
- Conditions
- Hepatocellular Injury, Blood Loss
- Being tested
- Pringle manoeuvre 15 minutes, Pringle manoeuvre 30 minutes
- Keywords
- liver surgery, pringle manoeuvre, hepatocellular damage, surgical complications, patients requiring liver surgery
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pringle manoeuvre 15 minutesProcedure or surgery
During parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 2-times 15 minutes with 5 minutes reperfusion
Pringle manoeuvre 30 minutesProcedure or surgery
During parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 30 minutes with 5 minutes reperfusion
| Study group | Role | What they receive |
|---|---|---|
| Pringle manoeuvre 15 minutes | Experimental | When intermittent pedicle occlusion during parenchymal transection is necessary, 2 cycles of 15 minutes of hepatic inflow occlusion will be applied each followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling. Receives: Procedure: Pringle manoeuvre 15 minutes |
| Pringle manoeuvre 30 minutes | Experimental | When intermittent pedicle occlusion during parenchymal transection is necessary, 1 cycle of 30 minutes of hepatic inflow occlusion will be applied followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling. Receives: Procedure: Pringle manoeuvre 30 minutes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatocellular Damage Reflected by Liver Fatty-acid Binding Protein (L-FABP) Levels
At specific time points before, during and after liver surgery, plasma samples will be obtained to analyse the amount of hepatocellular damage reflected by L-FABP) level. These timepoints include: baseline (before operation), just before intermittent pedicle clamping, just before end of 15 or 30 minutes pedicle clamping, end of 5 minutes reperfusion, end of liver surgery, 8 hours after start liver surgery, postoperative day 1, 2 and 3. This continuous variable with repeated measurements was summarized as area under the curve (AUC) from baseline to postoperative day 3 (as described in Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Bmj 1990;300:230-5).
Measured: L-FABP area under curve from start of surgery up until postoperative day 3
Secondary outcomes (3)
Post-resectional Complications
morbidity and mortality occuring after liver surgery graded according to Clavien-Dindo's grading system. In short, any deviation from the postoperative course without the need for pharmacological, radiological or surgical intervention was classified as Clavien-Dindo grade 1; complications requiring pharmacological treatment were graded as grade 2; complications requiring surgical or radiological intervention not under general anesthesia as grade 3a and under general anesthesia as grade 3b; grade 4 complications were life-threatening complications requiring intensive care unit care because of single organ dysfunction (grade 4a) or multiple organ dysfunction (grade 4b); mortality was classed as grade 5.
Measured: within 90-days after initial liver surgery
Amount of Blood Loss
amount of blood in the suction container (and, if applicable, in the weighted gauzes)
Measured: at the end of liver surgery, an average of 225 minutes
Hepatocellular Damage Reflected by Alanine Aminotransferase (ALAT) Levels
At specific time points before, during and after liver surgery, plasma samples will be obtained to analyse the amount of hepatocellular damage reflected by ALAT level. These timepoints include: baseline (before operation), just before intermittent pedicle clamping, just before end of 15 or 30 minutes pedicle clamping, end of 5 minutes reperfusion, end of liver surgery, 8 hours after start liver surgery, postoperative day 1, 2 and 3.
Measured: ALAT area under curve from start of surgery up until postoperative day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2010 (estimated)
- Study startOct 2007
- Primary completionJul 2009
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular InjuryStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cornelis HC Dejong, MD, PhD, Principal investigator, Maastricht University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01099475
- Sponsor's protocol ID
- 06-2-067
- Status last verified
- Oct 2014
- First submitted
- 1 Apr 2010
- Last updated
- 17 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
van den Broek MA, Bloemen JG, Dello SA, van de Poll MC, Olde Damink SW, Dejong CH. Randomized controlled trial analyzing the effect of 15 or 30 min intermittent Pringle maneuver on hepatocellular damage during liver surgery. J Hepatol. 2011 Aug;55(2):337-45. doi: 10.1016/j.jhep.2010.11.024. Epub 2010 Dec 13.
PubMed 21147188Dello SA, Reisinger KW, van Dam RM, Bemelmans MH, van Kuppevelt TH, van den Broek MA, Olde Damink SW, Poeze M, Buurman WA, Dejong CH. Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia. PLoS One. 2012;7(1):e30539. doi: 10.1371/journal.pone.0030539. Epub 2012 Jan 24.
PubMed 22291982
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial on the Effect of Intermittent Pedicle Clamping Using 15 or 30 Minutes Ischemic Intervals During Liver Surgery
- ClinicalTrials.gov ID
- NCT01099475
- Acronym / sponsor ID
- 06-2-067
- Conditions
- Hepatocellular Injury, Blood Loss
- Keywords
- liver surgery, pringle manoeuvre, hepatocellular damage, surgical complications, patients requiring liver surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 7 Apr 2010 (estimated)
- Results
- Posted 17 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In order to prevent excessive blood loss during liver surgery, an intermittent Pringle manoeuvre (IPM) can be applied. This implies a temporary clamping of the portal vein and hepatic artery in the hepatoduodenal ligament in order to occlude hepatic inflow. The optimal duration of the IPM is unknown. This randomized controlled trial aimed to analyse differences in hepatocellular damage after 15 minutes or 30 minutes IPM during liver surgery for primary or secondary liver tumours.
Detailed description
Surgical procedure Patients were anaesthetized using isoflurane and propofol. They routinely had an epidural catheter, urinary catheter, two peripheral venous catheters and indwelling catheters in a jugular vein and radial artery. Body temperature was maintained using a Bair Hugger system (Arizant Healthcare Inc. Eden Prairie, Minnesota).
The surgical procedure was performed using a subcostal bilateral incision and Olivier retractors to improve exposure. After dissection of the teres hepatis ligament, the liver was mobilized. Thereafter, an intra-operative ultrasound was performed to define the position of the tumour in relation to vascular and biliary structures. As IPM was not routinely applied, a patient was randomized for 15 minted IPM (15IPM) or 30 minutes IPM (30IPM) only after the surgeon had decided a complete Pringle manoeuvre would be required. During 15IPM or 30IPM, the complete portal triad was clamped using a rubber sling. The time of inflow occlusion was adapted to the need according to the randomization protocol. Occasionally, the left or right pedicle was ligated after protocolled IPM. Five minutes reperfusion intervals were applied during which transection was stopped and cut surfaces were gently compressed to ensure hemostasis. A Cavitron Ultrasonic Surgical Aspirator (CUSA system 200 macrodissector, Cavitron Surgical Systems, Stamford, Connecticut) and Argon beam coagulation (Force GSU System, Valleylab, Boulder, Colorado) were used for liver transection. A stapler device or clamps were used for transection of the hepatic veins. Central venous pressure was maintained below 5 centimetre of water (cm H2O) during transection to reduce venous back-bleeding. After surgery, the weight of the resection specimen was recorded. Perioperative care was protocolled, as described earlier.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pringle manoeuvre 15 minutes | Experimental | Procedure: Pringle manoeuvre 15 minutesWhen intermittent pedicle occlusion during parenchymal transection is necessary, 2 cycles of 15 minutes of hepatic inflow occlusion will be applied each followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling. |
| Pringle manoeuvre 30 minutes | Experimental | Procedure: Pringle manoeuvre 30 minutesWhen intermittent pedicle occlusion during parenchymal transection is necessary, 1 cycle of 30 minutes of hepatic inflow occlusion will be applied followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- patients > 18 years of age and < 100 years of age
- primary or secondary liver tumours requiring liver surgery
Key exclusion criteria (5 listed)
- pre-existent liver disease (e.g. inflammatory liver disease, cirrhosis, inborn errors of metabolism)
- cholangiocarcinoma requiring biliary tract reconstruction during surgery
- steroid hormone medication
- tumours deemed irresectable during liver surgery
- laparoscopic liver surgery
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 |
|---|---|---|
| Pringle manoeuvre 15 minutesDuring parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 2-times 15 minutes with 5 minutes reperfusion | Procedure or surgery | Pringle manoeuvre 15 minutes |
| Pringle manoeuvre 30 minutesDuring parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 30 minutes with 5 minutes reperfusion | Procedure or surgery | Pringle manoeuvre 30 minutes |
Primary outcome
Hepatocellular Damage Reflected by Liver Fatty-acid Binding Protein (L-FABP) Levels
Time frame: L-FABP area under curve from start of surgery up until postoperative day 3
At specific time points before, during and after liver surgery, plasma samples will be obtained to analyse the amount of hepatocellular damage reflected by L-FABP) level. These timepoints include: baseline (before operation), just before intermittent pedicle clamping, just before end of 15 or 30 minutes pedicle clamping, end of 5 minutes reperfusion, end of liver surgery, 8 hours after start liver surgery, postoperative day 1, 2 and 3. This continuous variable with repeated measurements was summarized as area under the curve (AUC) from baseline to postoperative day 3 (as described in Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Bmj 1990;300:230-5).
3 secondary outcomes
Post-resectional Complications
Time frame: within 90-days after initial liver surgery
Amount of Blood Loss
Time frame: at the end of liver surgery, an average of 225 minutes
Hepatocellular Damage Reflected by Alanine Aminotransferase (ALAT) Levels
Time frame: ALAT area under curve from start of surgery up until postoperative day 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21147188van den Broek MA, Bloemen JG, Dello SA, van de Poll MC, Olde Damink SW, Dejong CH. Randomized controlled trial analyzing the effect of 15 or 30 min intermittent Pringle maneuver on hepatocellular damage during liver surgery. J Hepatol. 2011 Aug;55(2):337-45. doi: 10.1016/j.jhep.2010.11.024. Epub 2010 Dec 13.
- Results publication: PubMed 22291982Dello SA, Reisinger KW, van Dam RM, Bemelmans MH, van Kuppevelt TH, van den Broek MA, Olde Damink SW, Poeze M, Buurman WA, Dejong CH. Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia. PLoS One. 2012;7(1):e30539. doi: 10.1371/journal.pone.0030539. Epub 2012 Jan 24.
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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.
Cornelis HC Dejong, MD, PhD principal investigator
Maastricht University Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pringle manoeuvre 15 minutes and Pringle manoeuvre 30 minutes in people with Hepatocellular Injury and Blood Loss, run by Maastricht University Medical Center at 1 site in Netherlands.
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 2 inclusion and 5 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: finished, as of the sponsor's last update on 17 Oct 2014. 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 Netherlands. 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?
Yes. Results are posted in the registry (first posted 17 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hepatocellular Damage Reflected by Liver Fatty-acid Binding Protein (L-FABP) Levels (time frame: L-FABP area under curve from start of surgery up until postoperative day 3). 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 NCT01099475, 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 17 Oct 2014.