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

Aortic Aneurysm Clinical Trial

— CLARIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02570464
• Other study ID #: 2010/147/HP
• Status: Recruiting
• Phase: N/A
• First received: October 2, 2015
• Last updated: October 5, 2015
• Start date: March 2012
• Est. completion date: December 2015

Study information

• Verified date: October 2015
• Source: University Hospital, Rouen
• Contact: Marie-Melody DUSSEAUX, MD
• Email: marie-melody.dusseaux[@]chu-rouen.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Aortic Aneurysm

Intervention

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

Locations

Country	Name	City	State
France	Rouen University Hospital	Rouen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood TNF-alpha rate	Blood TNF-alpha rate is measured after reperfusion	24 hours post-surgery	No
Secondary	Blood lactates rate	Blood lactates rate is measured after reperfusion	24 hours post-surgery	No
Secondary	Blood I-CAM protein rate	Blood I-CAM protein rate is measured after reperfusion	24 hours post-surgery	No
Secondary	Blood Interleukines 1 rate	Blood Interleukines 1 rate is measured after reperfusion	24 hours post-surgery	No
Secondary	Blood Interleukines 4 rate		24 hours post-surgery	No
Secondary	Blood Interleukines 6 rate	Blood Interleukines 1 rate is measured after reperfusion	24 hours post-surgery	No
Secondary	Blood Interleukines 10 rate	Blood Interleukines 10 rate is measured after reperfusion	24 hours post-surgery	No