Aortic Cross-Clamping and Systemic Inflammatory Response in Humans: Effect of Ischemic Preconditioning (CLARIS)

May 10, 2016 updated by: University Hospital, Rouen

Multiple organ dysfunction syndrome is a major cause of morbidity and mortality after abdominal aortic aneurysm (AAA) surgery. It is postulated that aortic cross-clamping during open AAA repair may cause ischemia-reperfusion (I/R) leading to the systemic releases of reactive oxygen species (ROS) and inflammatory cytokines which damage distant organs, including heart, kidney, and lung.

Ischemic preconditioning, first described in cardiac surgery, is a mechanism whereby tissues exposed to a brief period of nonlethal I/R develop resistance to subsequent ischemic insult. Remote ischemic preconditioning (RIPC), is a phenomenon whereby brief periods of ischemia followed by reperfusion in one organ (usually skeletal muscle) provide systemic protection from prolonged ischemia. The mechanisms through which RIPC confer organ protection remains unclear.

The hypothesis is that limb RIPC would reduce systemic inflammatory mediators produced by ischemia-reperfusion and thereby protect the remote organs.

A single-center, prospective, randomized, parallel-group controlled trial is conducted on patients undergoing elective open infrarenal AAA repair. Written informed consent is obtained from each participant. The study protocol was reviewed and approved by the Research Ethics Committee of Rouen, France.

Patients are divided in two groups : the sham-operated control group underwent surgery without RIPC and the RIPC group : Two cycles of intermittent crossclamping of the common iliac artery (right or left) with 10 minutes ischemia followed by 10 minutes reperfusion served as the RIPC stimulus, before prolonged ischemia.

Blood samples are collected for analysis at the following time points: before surgery (baseline), 1, 3 and 24 h after cross-clamp release (reperfusion). The systemic inflammatory response is measured using the serum concentrations of TNF-alpha, and IL 1, 4, 6, 10. Cardiac, renal and pulmonary functions are evaluated with usual biological markers and clinical monitoring until 28 days after surgery.

Aortic surgery is a perfect clinical model of ischemia-reperfusion which makes it possible to study the impact of RIPC in humans. This biological approach would help to better understand the mechanisms underlying this technique.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Rouen, France, 76031
        • Rouen University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients undergoing elective open infrarenal abdominal aortic aneurysm repair
  • Scheduled surgery
  • Patients aged 30-85 years old

Exclusion Criteria:

  • Patients undergoing endovascular treatment for infrarenal abdominal aortic aneurysm
  • Patients younger than 30 years and older than 85 years
  • pregnant women or nursing mother
  • Adult under guardianship
  • Refusal to sign a consent
  • Patients whose survival at 28 days is unlikely
  • Surgery requiring subphrenic aortic cross-clamping
  • Emergency surgery
  • Patients taking sulfonylureas or Nicorandil
  • Patients having contraindication to clamp iliac arteries
  • Dementia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients undergoing aortic aneurysm surgery with RIPC
Blood drawn is done for patient undergoing elective open infrarenal abdominal aortic aneurysm repair surgery with Remote ischemic preconditioning (RIPC)
Procedure: Remote ischemic preconditioning
Remote ischemic preconditioning is done for patients undergoing elective open infrarenal abdominal aortic aneurysm repair
Biological: Blood drawn
Blood drawn is done for patients undergoing elective open infrarenal abdominal aortic aneurysm repair
Sham Comparator: Patients undergoing aortic aneurysm surgery without RIPC
Blood drawn is done for patient undergoing elective open infrarenal abdominal aortic aneurysm repair surgery without Remote ischemic preconditioning (RIPC)
Biological: Blood drawn
Blood drawn is done for patients undergoing elective open infrarenal abdominal aortic aneurysm repair

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood TNF-alpha rate
Time Frame: 24 hours post-surgery
Blood TNF-alpha rate is measured after reperfusion
24 hours post-surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood lactates rate
Time Frame: 24 hours post-surgery
Blood lactates rate is measured after reperfusion
24 hours post-surgery
Blood I-CAM protein rate
Time Frame: 24 hours post-surgery
Blood I-CAM protein rate is measured after reperfusion
24 hours post-surgery
Blood Interleukines 1 rate
Time Frame: 24 hours post-surgery
Blood Interleukines 1 rate is measured after reperfusion
24 hours post-surgery
Blood Interleukines 4 rate
Time Frame: 24 hours post-surgery
24 hours post-surgery
Blood Interleukines 6 rate
Time Frame: 24 hours post-surgery
Blood Interleukines 1 rate is measured after reperfusion
24 hours post-surgery
Blood Interleukines 10 rate
Time Frame: 24 hours post-surgery
Blood Interleukines 10 rate is measured after reperfusion
24 hours post-surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Rouen

Investigators

  • Principal Investigator: Marie-Melody DUSSEAUX, MD, Rouen University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

October 2, 2015

First Submitted That Met QC Criteria

October 5, 2015

First Posted (Estimate)

October 7, 2015

Study Record Updates

Last Update Posted (Estimate)

May 12, 2016

Last Update Submitted That Met QC Criteria

May 10, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010/147/HP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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