Isoflurane Preconditioning for Liver Resections
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ClinicalTrials.gov Identifier: NCT01031550 |
Recruitment Status
:
Terminated
(We no longer had an appropriate patient population.Study closed)
First Posted
: December 14, 2009
Results First Posted
: December 12, 2013
Last Update Posted
: March 20, 2017
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Tracking Information | ||||
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First Submitted Date ICMJE | December 10, 2009 | |||
First Posted Date ICMJE | December 14, 2009 | |||
Results First Submitted Date | September 16, 2013 | |||
Results First Posted Date | December 12, 2013 | |||
Last Update Posted Date | March 20, 2017 | |||
Study Start Date ICMJE | January 2010 | |||
Actual Primary Completion Date | January 2012 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Post Operative Complications Grade IIIb or Greater According to Clavien's Classification Which is a Classification System Used to Grade Surgical Complications [ Time Frame: first 7 post operative days ] Post operative complications grade IIIB or greater according to Clavien's classification: IIIb=complication necessitating an intervention under general anesthesia; Grade IV=Life threatening complications requiring ICU management, IV a =single organ dysfunction, IVb=multi-organ dysfunction; V=death Suffix d(disability)=subject suffers from complication at time of discharge. This label indicates the need for a follow up to fully evaluate the complication.
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Original Primary Outcome Measures ICMJE |
Post Operative Complications Grade IIIb or Greater According to Clavien's Classification [ Time Frame: first 7 post operative days ] | |||
Change History | Complete list of historical versions of study NCT01031550 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
peak postoperative AST, ALT and T Bili, length of ICU and Hosp[ital stay, decrease in liver lipid peroxidation and apoptosis. [ Time Frame: first 7 post operative days ] | |||
Current Other Outcome Measures ICMJE | Not Provided | |||
Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Isoflurane Preconditioning for Liver Resections | |||
Official Title ICMJE | Isoflurane Induced Anesthetic Preconditioning in Elective Liver Resection | |||
Brief Summary | The objective is to examine the efficacy of isoflurane (inhaled anesthetic gas) to induce clinically effective preconditioning in patients undergoing elective hepatic surgery. | |||
Detailed Description | Elective liver resection is performed primarily for the treatment of benign and malignant liver tumors1. In addition, with the increasing use of living donor liver transplantation to supplement the inadequate pool of cadaveric organs available, liver resection is performed also in live liver donors2. Postoperative complications are common following liver resections. Occurrence of complications increases ICU and hospital stay, and resource utilization. The most serious postoperative complication after a liver resection is post-resectional liver failure (PLF)3. Risk factors for the development of PLF are preexisting liver disease, especially cirrhosis, excessive blood loss during liver resection, and liver ischemia and reperfusion injury4-5. Several strategies have been developed to combat excessive intra-operative blood loss including: lowering the central venous pressure6, hypoventilation7, and hepatic inflow occlusion using an atraumatic clamp8 (Pringle's maneuver)9; While inflow occlusion is the most important of these steps, hepatic ischemia and reperfusion is an important sequel to the inflow occlusion. Therefore, interventions which decrease hepatic ischemia reperfusion injury to the liver have the potential to improve outcomes following liver resection. A strategy that directly modulates the hepatic response to ischemia is ischemic preconditioning (IPC). Classically, IPC has been induced by exposing an organ to brief periods of ischemia and reperfusion before exposing the organ to a more prolonged ischemic insult. In patients undergoing liver resection, IPC decreases postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels15. IPC is also associated with decreased histological evidence of apoptosis as well as immunohistochemical evidence of increased protective gene expression16 in the liver. The primary disadvantage of IPC is the direct stress to the target organ as well as the mechanical trauma to major vasculature. More recently, it has been found that inhaled volatile anesthetics such as Desflurane, Sevoflurane and Isoflurane induce similar preconditioning effects19 without causing any significant direct organ damage. While several animal studies exist, which demonstrate the hepatoprotective effect of volatile anesthetics on the liver23, there is only limited clinical data examining their effect in humans. One recent small clinical study, examining the preconditioning effect of volatile anesthetic on patients undergoing liver surgery, showed that anesthetic pre conditioning (APC) using Sevoflurane significantly decreased the several measures of liver dysfunction postoperatively24. However, Sevoflurane is partially metabolized by the liver and may increase plasma fluoride concentration. Also, it may react with CO2 absorbent and can produce Compound-A, which in turn has been linked to nephrotoxicity. On the other hand, isoflurane, another inhalational anesthetic agent commonly used during liver surgery also has been shown to have a preconditioning effect in experimental animals, and does not carry the potential side effects of sevoflurane. Therefore, the primary objective of this study is to examine the efficacy of isoflurane to induce clinically effective preconditioning in patients undergoing elective hepatic surgery. Study Design: In this prospective study, patients undergoing elective liver resection with inflow occlusion (Pringle maneuver) at UH, Newark will be randomized (1:1) to either standard anesthetic management with Propofol (No APC group) or anesthetic preconditioning with 2 minimum alveolar concentration (MAC) of isoflurane (APC group). Because preexisting liver disease, especially cirrhosis, is an important determinant of post operative outcomes, and to balance the randomization of subjects regarding this important variable randomization will be stratified into those with and without preexisting liver disease. The primary endpoint is the occurrence of postoperative complications grade IIIb or greater (Clavien's classification). The secondary endpoints are peak postoperative aspartate and alanine aminotransferase (AST and ALT) and total bilirubin (T Bili), length of ICU and hospital stay, and a decrease in liver lipid peroxidation and apoptosis |
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Study Type ICMJE | Interventional | |||
Study Phase | Not Applicable | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Liver Disease | |||
Intervention ICMJE |
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Study Arms |
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Terminated | |||
Actual Enrollment ICMJE |
8 | |||
Original Estimated Enrollment ICMJE |
64 | |||
Actual Study Completion Date | June 2012 | |||
Actual Primary Completion Date | January 2012 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Senior) | |||
Accepts Healthy Volunteers | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01031550 | |||
Other Study ID Numbers ICMJE | 0120090226 | |||
Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement |
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Responsible Party | Yuriy Gubenko, MD, Rutgers, The State University of New Jersey | |||
Study Sponsor ICMJE | Rutgers, The State University of New Jersey | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | Rutgers, The State University of New Jersey | |||
Verification Date | February 2017 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |