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Ischemia Reperfusion InjuryNCT03848780

Desflurane Preconditioning in Hepatectomies

A study testing Desflurane in people with Ischemia Reperfusion Injury, run by Aristotle University Of Thessaloniki.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Hepatectomies are considered as operations of high bleeding risk. The history of massive hemorrhage in liver surgery led to the emergence of techniques to control excessive blood loss. These techniques temporarily occlude the blood vessels that supply liver (the Pringle Maneuver) limiting subsequent losses. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ischemia Reperfusion Injury
What is being tested?
Desflurane
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
No sites listed yet
Study dates
1 Apr 2016to 30 Jun 2018
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

  • hepatectomy of at least two segments

Who cannot join

  • Hepatitis B, C or HIV infection
  • liver cirrhosis
  • autoimmune disease, inflammatory bowel disease
  • pregnancy
  • prior additional ablation therapies (cryosurgery or radiofrequency)
  • liver resections without inflow occlusion

About this study

Official title: Pharmacological Preconditioning With Desflurane in Liver Surgery

Hepatectomies are considered as operations of high bleeding risk. The history of massive hemorrhage in liver surgery led to the emergence of techniques to control excessive blood loss. These techniques temporarily occlude the blood vessels that supply liver (the Pringle Maneuver) limiting subsequent losses. However, this leads to the ischemia - reperfusion injury impairing liver function. Research points to methods targeting on tempering reperfusion pathophysiology. Volatile anesthetics have been used for pharmacological preconditioning and proved to protect against organ damage. The aim of this study was to investigate the potential beneficial effect of desflurane on ischemia-reperfusion injury of the liver. Patients presenting for elective hepatectomy were randomized equally into two groups. The Control Group received no pharmacological preconditioning and the Desflurane Group received pharmacological preconditioning with Desflurane before induction of ischemia.

Read the detailed description

Hepatectomies are characterized by an elevated risk of severe hemorrhage. The high vascular supply of the liver has historically troubled surgeons who resolved to techniques to control excessive blood loss. The Pringle Maneuver commonly employed in liver surgery is a temporary method to occlude the vascular supply of the liver. As a result, ischemia is developed and a pathophysiologic cascade is initiated. Upon the resolution of ischemia, reperfusion occurs which is linked to further damage and the ischemia-reperfusion injury is developed. Ischemia and reperfusion lead to activation of the innate immune response, which interacts with the adaptive immune response. Result of this interaction is the production of inflammatory cytokines, chemokines, complement products, and the recruitment of neutrophils to the site of injury. Previous studies have shown that animal's livers suffered from ischemia-reperfusion injury had increased neutrophil infiltration and pharmacological agents attenuating neutrophil's activity improved hepatic Ischemia-Reperfusion Injury (IRI). Preconditioning refers to the exposure of an organ to short intervals of ischemia which has been shown to mitigate the aforementioned ischemia-reperfusion injury. Preconditioning can be pharmacological and volatile anesthetics have been successfully used in preconditioning models. Sevoflurane have been proved beneficial for a series of hepatectomies in limiting transaminase levels postoperatively. However, sevoflurane by virtue can be hepatotoxic through Compound A production, elevated free calcium and reactive oxide species activation. On the other hand, desflurane undergoes minimum liver metabolism. In liver ischemia-reperfusion models, desflurane preconditioning led to decreased cell death and inflammatory cytokines inhibition.

The goal of the investigator's study was to investigate the effect of desflurane preconditioning in patients undergoing elective hepatectomy of at least two segments. Patients were randomized 1:1 to receive pharmacological preconditioning (Desflurane Group, Group D) or not (Control Group, Group C). The surgeon and the Intensive Care Unit were blinded as to the intervention. Anesthetic management was the same for all patients. For GroupD thirty minutes before the initiation of ischemia desflurane was delivered and propofol was stopped for the same interval.

Being tested
Desflurane
Keywords
preconditioning, hepatectomy, ischemia reperfusion injury
Medical subject headings
Reperfusion Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DesfluraneDrug

Study groups in NCT03848780
Study groupRoleWhat they receive
Desflurane GroupExperimentalThirty minutes before initiation of ischemia the surgeon was instructed to notify the anesthesiologist. At this single time point, propofol infusion was stopped and substituted with the volatile anesthetic desflurane to achieve a Minimum Alveolar Concentration of 1. The procedure included a 5-minute induction of desflurane, a 20-minute preconditioning and a 5-minute washout period when propofol was reintroduced and desflurane stopped.
Receives: Drug: Desflurane
Control GroupNo interventionNo pharmacological preconditioning was implemented

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Matrix Metalloproteinases (MMPs) 2 and 9 level

    The levels of Matrix Metalloproteinase 2 and Matrix Metalloproteinase 9 as evaluated by the relative gene expression using RT-PCR. The comparative CT method also referred to as the 2-ΔΔCT method was used to calculate the fold change and then convert it to percentage. Their presence has been linked to hepatic cellular injury so increased levels represent worse injury.

    Measured: Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion

  2. Tissue Inhibitor Metalloproteinase (TIMPs) 1and 2

    The levels of Tissue Inhibitor Metalloproteinase 1 and Tissue Inhibitor Metalloproteinase 2 as evaluated by the relative gene expression using RT-PCR. The comparative CT method also referred to as the 2-ΔΔCT method was used to calculate the fold change and then convert it to percentage. Their inhibitory effect on Matrix Metalloproteinases has been associated with a limitation of cellular injury. Thus, the higher the levels of Tissue Inhibitor Metalloproteinases the greater their protective activity.

    Measured: Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion

Secondary outcomes (1)

  1. Histological findings of hepatic parenchyma

    Hematoxylin Eosin, Gomori and Μasson staining were used. With Hematoxylin Eosin staining the degree of steatosis was assessed while Gomori and Masson staining was used to determine the level of fibrosis.

    Steatosis was characterized (x100 magnification) as mild (10%-30%), moderate (30%-60%), severe (>60%) according to the presence of fat droplets in hepatic cells.

    Fibrosis was also graded based on the METAVIR score as absent - F0, portal fibrosis without septa - F1, portal fibrosis with rare septa - F2, numerous septa - F3 and cirrhosis - F4.

    Measured: Sample 1: Upon surgical dissection of the liver, before inflow occlusion, Sample: thirty minutes after reperfusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2019
  2. Study start1 Apr 2016
  3. Primary completion30 Jun 2018
  4. Study completion30 Jun 2018

Resources

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
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03848780
Sponsor's protocol ID
3779
Status last verified
Feb 2019
First submitted
29 Jan 2019
Last updated
21 Feb 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rosen HR, Martin P, Goss J, Donovan J, Melinek J, Rudich S, Imagawa DK, Kinkhabwala M, Seu P, Busuttil RW, Shackleton CR. Significance of early aminotransferase elevation after liver transplantation. Transplantation. 1998 Jan 15;65(1):68-72. doi: 10.1097/00007890-199801150-00013.

    PubMed 9448146

  • Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Nozawa S, Furukawa K, Mitsuhashi N, Sawada S, Takeuchi D, Ambiru S, Miyazaki M. Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection. J Surg Res. 2006 Jun 15;133(2):102-12. doi: 10.1016/j.jss.2005.10.025. Epub 2006 Jan 4.

    PubMed 16386757

  • Boros P, Bromberg JS. New cellular and molecular immune pathways in ischemia/reperfusion injury. Am J Transplant. 2006 Apr;6(4):652-8. doi: 10.1111/j.1600-6143.2005.01228.x.

    PubMed 16539620

  • Beck-Schimmer B, Breitenstein S, Urech S, De Conno E, Wittlinger M, Puhan M, Jochum W, Spahn DR, Graf R, Clavien PA. A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic. Ann Surg. 2008 Dec;248(6):909-18. doi: 10.1097/SLA.0b013e31818f3dda.

    PubMed 19092335

Questions about this trial

What is this clinical trial studying?

A study testing Desflurane in people with Ischemia Reperfusion Injury, run by Aristotle University Of Thessaloniki.

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 6 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 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

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?

Matrix Metalloproteinases (MMPs) 2 and 9 level (time frame: Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion). The study lists 2 primary outcomes in all. 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 NCT03848780, 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 21 Feb 2019.

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