Statin Use in Abdominal Aortic Aneurysm Repair
Aneurysm formation is associated with a chronic inflammatory response, depletion of smooth muscle cell population and excessive matrix metalloproteinases (MMPs) production. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are lipid lowering agents with pleiotropic effects including anti-inflammatory activity. Elective open AAA repair patients will be randomised to receive either statin (Atorvastatin 80 mg) or placebo (dummy tablet) for 4 weeks pre-operatively. Tissue samples will be obtained from patient's aneurysm to assess MMP's and their inhibitors TIMP's. It is hypothesized that patients receiving statin will have reduced MMP's.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
|Official Title:||Randomised Controlled Trial of Effect of Pre-operative Statin Use on Matrix Metalloproteinases (MMP) & Tissue Inhibitors of Matrix Metalloproteinases (TIMP) in Abdominal Aortic Aneurysm (AAA).|
- The primary outcome measure was the level of MMP-9 in aortic wall samples of patients on statins and placebo. [ Time Frame: Sample obtained at time of operation ] [ Designated as safety issue: No ]
- The secondary outcome measures were the levels of MMP-2, MMP-8, TIMP-1, TIMP-2 and the variation in areas of peak wall stress due to statins. [ Time Frame: Sample obtained at time of operation ] [ Designated as safety issue: No ]
|Study Start Date:||January 2005|
|Study Completion Date:||December 2008|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
Placebo given once daily for 4 weeks.
|Active Comparator: Statin group||
Atorvastatin 80mg, once a day for four weeks.
All patients listed for elective open AAA repair will be screened for suitability to participate within the study. In this double blind randomized control trial patients will be recruited through vascular surgical outpatient clinics. After inclusion, informed consent and evaluation of base line characteristics patients will be given a prescription for study medication. This prescription was exchanged by the patient for medication at the hospital pharmacy. Randomization will be carried out by pharmacy with computer generated sequence with a sub group size of 4. This will ascertain the order of prescribed drug/ placebo. Pharmacy then dispensed the drug/ placebo in this order. Drug used will be Atorvastatin 80 mg, white, elliptical, film coated tablets debossed '80' on one side and 'PD 158' on the other side. The placebo is similar in shape and colour. Drug/ placebo will be given for 4 weeks pre-operatively. Full thickness infrarenal aortic samples will obtained at time of operation and the exact sample site will be recorded. Samples will be washed with 0.9% saline to remove blood and clots, snap-frozen and stored at -80C for subsequent MMP 2, 8 and 9 and TIMP 1 and 2 analyses.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01062802
|Hull & east Yorkshire Hospitals NHS Trust|
|Hull, United Kingdom, HU3 2JZ|
|Principal Investigator:||Ian C Chetter, MBChB, FRCS||Hull Royal Infirmary, Hull, United Kingdom.|