Clinical trial NCT02570464: Aortic Cross-Clamping and Systemic Inflammatory Response in Humans: Effect of Ischemic Preconditioning
Official title: Aortic Cross-Clamping and Systemic Inflammatory Response in Humans: Effect of Ischemic Preconditioning
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Aneurysm
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
First posted: 2015-10-07
Enrollment: 68
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Blood TNF-alpha rate
timeFrame: 24 hours post-surgery
Secondary outcomes:
measure: Blood lactates rate
timeFrame: 24 hours post-surgery
measure: Blood I-CAM protein rate
timeFrame: 24 hours post-surgery
measure: Blood Interleukines 1 rate
timeFrame: 24 hours post-surgery
measure: Blood Interleukines 4 rate
timeFrame: 24 hours post-surgery
measure: Blood Interleukines 6 rate
timeFrame: 24 hours post-surgery
measure: Blood Interleukines 10 rate
timeFrame: 24 hours post-surgery
Other outcomes:
Locations:
city: Rouen
country: France
facility: Rouen University Hospital
Study officials:
affiliation: University Hospital, Rouen
name: Marie-Melody DUSSEAUX, MD
role: PRINCIPAL_INVESTIGATOR
References: