Hepatic Ischemia-reperfusion InjuryNCT01499979
Hypothermic Perfusion During Hemihepatectomy
A study testing In situ hypothermic perfusion in people with Hepatic Ischemia-reperfusion Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Rationale Currently, hepatic resection is often the only curative treatment for primary or secondary hepatic malignancies and is also frequently performed in patients with benign liver tumors to prevent malignant transformation and/or alleviate symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Ischemia-reperfusion Injury
- What is being tested?
- In situ hypothermic perfusion
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2012to Aug 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients scheduled for right hemihepatectomy under vascular inflow occlusion for a malignant or benign hepatic tumor
- Diagnostic exclusion of hepatic co-morbidity, that is:
- Cirrhosis,
- Severe steatosis (≥ 30%),
- Cholestasis, and
- Hepatitis B/C infection
Show all 9Show fewer
- Age ≥ 18 years
- Signed informed consent obtained prior to any study-specific procedure
- ASA classification I-III
Who cannot join
- Patients diagnosed with any of the hepatic co-morbidities listed under point 2 of the inclusion criteria
- Age < 18 years
- BMI > 35 kg/m2
- ASA classification IV/V
- Patient is scheduled for a combined surgical procedure (e.g., bile duct resection, gastrointestinal procedures)
- Patient underwent liver resection ≤ 1 year prior to scheduled surgery
- Emergency operations
- Pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center (AMC)
Amsterdam, North Holland, 1105 AZ
About this study
Official title: In Situ Hypothermic Perfusion During Right Hemihepatectomy
Rationale
Currently, hepatic resection is often the only curative treatment for primary or secondary hepatic malignancies and is also frequently performed in patients with benign liver tumors to prevent malignant transformation and/or alleviate symptoms. Liver resections are nowadays associated with low mortality and acceptable morbidity. As result of that, an increasing number of patients is currently under consideration for resection of more complex or large tumors, thus requiring extensive resection procedures. Application of vascular exclusion (i.e., clamping of the portal vein and hepatic artery) during such procedures reduces blood loss, which is one of the most important factors affecting peri-operative outcomes. However, vascular exclusion leads to ischemia-reperfusion (I/R) injury as an inevitable side-effect, which adversely impacts postoperative liver function and regeneration. Additional cooling of the liver by means of hypothermic perfusion is expected to further reduce intraoperative blood loss, as well as to protect the liver from I/R injury. Therefore, the aim of this pilot study is to cool the future remnant liver (FRL) in situ during right hemihepatectomy under vascular exclusion. Consequently, an overall improvement in postoperative outcomes is expected due to a decrease in intraoperative blood loss, reduced parenchymal damage, and a better ability of the liver remnant to regenerate.
Read more
Objective
To reduce intraoperative blood loss and enhance tolerance of the FRL to I/R injury during right hemihepatectomy under vascular exclusion by means of in situ hypothermic perfusion with retrograde outflow (R-IHP) of the FRL.
Study design
The study is designed as a prospective randomized pilot study in 18 patients (9 interventions and 9 controls) to assess the effects of the proposed intervention. Additionally, 4 patients will be included separately for assessment of the intervention's feasibility prior to randomized inclusion.
Study population
Eligible patients for participation in this study are those planned to undergo right hemihepatectomy under vascular inflow occlusion because of a malignant or benign liver tumor, and who do not suffer from any hepatic co-morbidity that might influence postoperative outcomes (i.e., severe steatosis, cholestasis, cirrhosis, or hepatitis B/C infection).
Intervention
During right hemihepatectomy, the FRL of patients allocated to the intervention group will be perfused with a chilled perfusion solution (i.e., lactated Ringer's solution).
- Conditions
- Hepatic Ischemia-reperfusion Injury
- Being tested
- In situ hypothermic perfusion
- Keywords
- Ischemia-reperfusion injury, In situ hypothermic perfusion, In situ hypothermic preservation
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
In situ hypothermic perfusionProcedure or surgery
Also called In situ hypothermic preservation
In situ perfusion of the future remnant liver with chilled lactated Ringer's solution during liver resection.
| Study group | Role | What they receive |
|---|---|---|
| Vascular inflow occlusion | No intervention | Patients that will receive intermittent vascular inflow occlusion, the standard method for vascular occlusion at our institution, during liver resection. |
| Hypothermic perfusion | Experimental | Patients will receive in situ hypothermic perfusion of the future remnant liver during liver resection. Receives: Procedure: In situ hypothermic perfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative hepatocellular damage
Hepatocellular damage expressed as an postoperative increase in transaminases (i.e., AST and ALT).
Measured: 5 days postoperatively
Secondary outcomes (3)
Intraoperative blood loss
Blood loss during surgery
Measured: 2-3 hours
Postoperative complications
Incidence of surgery-related complications
Measured: 5 days postoperatively
Regeneration of liver function and volume
Regeneration of liver function (measured via hepatobiliary scintigraphy) and -volume (measured via CT volumetry).
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startFeb 2012
- Primary completionMay 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatic 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Megan J. Reiniers, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Prof. Thomas M. van Gulik, MD, PhD, Study chair, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Megan J. Reiniers, MSc, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Rowan F. van Golen, MSc, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499979
- Sponsor's protocol ID
- 2011_214
- Other IDs
- NL37241.018.11
- Status last verified
- Jan 2016
- First submitted
- 20 Dec 2011
- Last updated
- 26 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Azoulay D, Eshkenazy R, Andreani P, Castaing D, Adam R, Ichai P, Naili S, Vinet E, Saliba F, Lemoine A, Gillon MC, Bismuth H. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg. 2005 Feb;241(2):277-85. doi: 10.1097/01.sla.0000152017.62778.2f.
PubMed 15650638Dinant S, van Veen SQ, Roseboom HJ, van Vliet AK, van Gulik TM. Liver protection by hypothermic perfusion at different temperatures during total vascular exclusion. Liver Int. 2006 May;26(4):486-93. doi: 10.1111/j.1478-3231.2006.01248.x.
PubMed 16629653Verhoef C, de Wilt JH, Brunstein F, Marinelli AW, van Etten B, Vermaas M, Guetens G, de Boeck G, de Bruijn EA, Eggermont AM. Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion. Ann Surg Oncol. 2008 May;15(5):1367-74. doi: 10.1245/s10434-007-9714-z. Epub 2008 Feb 1.
PubMed 18239976Reiniers MJ, van Golen RF, Heger M, Mearadji B, Bennink RJ, Verheij J, van Gulik TM. In situ hypothermic perfusion with retrograde outflow during right hemihepatectomy: first experiences with a new technique. J Am Coll Surg. 2014 Jan;218(1):e7-16. doi: 10.1016/j.jamcollsurg.2013.09.013. Epub 2013 Nov 6. No abstract available.
PubMed 24210146
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Situ Hypothermic Perfusion During Right Hemihepatectomy
- ClinicalTrials.gov ID
- NCT01499979
- Acronym / sponsor ID
- 2011_214
- Conditions
- Hepatic Ischemia-reperfusion Injury
- Keywords
- Ischemia-reperfusion injury, In situ hypothermic perfusion, In situ hypothermic preservation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Feb 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 26 Dec 2011 (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.
Rationale
Currently, hepatic resection is often the only curative treatment for primary or secondary hepatic malignancies and is also frequently performed in patients with benign liver tumors to prevent malignant transformation and/or alleviate symptoms. Liver resections are nowadays associated with low mortality and acceptable morbidity. As result of that, an increasing number of patients is currently under consideration for resection of more complex or large tumors, thus requiring extensive resection procedures. Application of vascular exclusion (i.e., clamping of the portal vein and hepatic artery) during such procedures reduces blood loss, which is one of the most important factors affecting peri-operative outcomes. However, vascular exclusion leads to ischemia-reperfusion (I/R) injury as an inevitable side-effect, which adversely impacts postoperative liver function and regeneration. Additional cooling of the liver by means of hypothermic perfusion is expected to further reduce intraoperative blood loss, as well as to protect the liver from I/R injury. Therefore, the aim of this pilot study is to cool the future remnant liver (FRL) in situ during right hemihepatectomy under vascular exclusion. Consequently, an overall improvement in postoperative outcomes is expected due to a decrease in intraoperative blood loss, reduced parenchymal damage, and a better ability of the liver remnant to regenerate.
Objective
To reduce intraoperative blood loss and enhance tolerance of the FRL to I/R injury during right hemihepatectomy under vascular exclusion by means of in situ hypothermic perfusion with retrograde outflow (R-IHP) of the FRL.
Study design
The study is designed as a prospective randomized pilot study in 18 patients (9 interventions and 9 controls) to assess the effects of the proposed intervention. Additionally, 4 patients will be included separately for assessment of the intervention's feasibility prior to randomized inclusion.
Study population
Eligible patients for participation in this study are those planned to undergo right hemihepatectomy under vascular inflow occlusion because of a malignant or benign liver tumor, and who do not suffer from any hepatic co-morbidity that might influence postoperative outcomes (i.e., severe steatosis, cholestasis, cirrhosis, or hepatitis B/C infection).
Intervention
During right hemihepatectomy, the FRL of patients allocated to the intervention group will be perfused with a chilled perfusion solution (i.e., lactated Ringer's solution).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vascular inflow occlusion | No intervention | –Patients that will receive intermittent vascular inflow occlusion, the standard method for vascular occlusion at our institution, during liver resection. |
| Hypothermic perfusion | Experimental | Procedure: In situ hypothermic perfusionPatients will receive in situ hypothermic perfusion of the future remnant liver during liver resection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients scheduled for right hemihepatectomy under vascular inflow occlusion for a malignant or benign hepatic tumor
- Diagnostic exclusion of hepatic co-morbidity, that is:
- Age ≥ 18 years
- Signed informed consent obtained prior to any study-specific procedure
- ASA classification I-III
Key exclusion criteria (8 listed)
- Patients diagnosed with any of the hepatic co-morbidities listed under point 2 of the inclusion criteria
- Age < 18 years
- BMI > 35 kg/m2
- ASA classification IV/V
- Patient is scheduled for a combined surgical procedure (e.g., bile duct resection, gastrointestinal procedures)
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 |
|---|---|---|
| In situ hypothermic perfusionAlso: In situ hypothermic preservationIn situ perfusion of the future remnant liver with chilled lactated Ringer's solution during liver resection. | Procedure or surgery | Hypothermic perfusion |
Primary outcome
Postoperative hepatocellular damage
Time frame: 5 days postoperatively
Hepatocellular damage expressed as an postoperative increase in transaminases (i.e., AST and ALT).
3 secondary outcomes
Intraoperative blood loss
Time frame: 2-3 hours
Postoperative complications
Time frame: 5 days postoperatively
Regeneration of liver function and volume
Time frame: 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2016.
- Background: PubMed 15650638Azoulay D, Eshkenazy R, Andreani P, Castaing D, Adam R, Ichai P, Naili S, Vinet E, Saliba F, Lemoine A, Gillon MC, Bismuth H. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg. 2005 Feb;241(2):277-85. doi: 10.1097/01.sla.0000152017.62778.2f.
- Background: PubMed 16629653Dinant S, van Veen SQ, Roseboom HJ, van Vliet AK, van Gulik TM. Liver protection by hypothermic perfusion at different temperatures during total vascular exclusion. Liver Int. 2006 May;26(4):486-93. doi: 10.1111/j.1478-3231.2006.01248.x.
- Background: PubMed 18239976Verhoef C, de Wilt JH, Brunstein F, Marinelli AW, van Etten B, Vermaas M, Guetens G, de Boeck G, de Bruijn EA, Eggermont AM. Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion. Ann Surg Oncol. 2008 May;15(5):1367-74. doi: 10.1245/s10434-007-9714-z. Epub 2008 Feb 1.
- Results publication: PubMed 24210146Reiniers MJ, van Golen RF, Heger M, Mearadji B, Bennink RJ, Verheij J, van Gulik TM. In situ hypothermic perfusion with retrograde outflow during right hemihepatectomy: first experiences with a new technique. J Am Coll Surg. 2014 Jan;218(1):e7-16. doi: 10.1016/j.jamcollsurg.2013.09.013. Epub 2013 Nov 6. No abstract available.
- Individual participant dataSharing planned: Undecided
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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.
Prof. Thomas M. van Gulik, MD, PhD study chair
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Megan J. Reiniers, MSc principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Rowan F. van Golen, MSc principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing In situ hypothermic perfusion in people with Hepatic Ischemia-reperfusion Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) 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 9 inclusion and 8 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 26 Jan 2016. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Postoperative hepatocellular damage (time frame: 5 days postoperatively). 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 NCT01499979, which also lists 4 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 26 Jan 2016.