Metabolic Support With Perhexiline to Protect Myocardium Undergoing Coronary Artery Surgery

Overview

Open-heart surgery causes injury of the heart muscle. Although this is usually mild, temporary and reversible, if it is severe it can endanger life and require additional high cost care. During surgery, techniques are used to protect the heart from injury, but these remain imperfect. This study assesses the effect of facilitating sugar metabolism (a more efficient fuel) by the heart muscle using the drug Perhexiline given before the operation. This treatment has a sound experimental basis for improving outcome. If this improvement is confirmed surgical results could be improved. The investigators will be studying heart function, heart muscle energy stores and chemicals which quantify the amount of heart muscle injury. The investigators' hypothesis is that Perhexiline will improve the protection of the heart by decreasing damage that may occur during heart surgery.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: April 2010

Interventions

  • Drug: Perhexiline
    • Tablets. Dose: 200mg BD for 3 days, then 100mg BD until surgery. Duration of therapy: 5-31 days.
  • Drug: Placebo marked PEXSIG
    • Tablets. Dose: 200mg BD for 3 days, then 100mg BD until surgery. Duration of therapy: 5-31 days.

Arms, Groups and Cohorts

  • Experimental: Perhexiline
    • Pre-operative administration of Perhexiline tablets according to dosing schedule
  • Placebo Comparator: Placebo
    • Pre-operative administration of placebo tablets according to dosing schedule

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of Low Cardiac Output Syndrome
    • Time Frame: 6 hours post-removal of aortic X-clamp

Secondary Measures

  • Increase in Cardiac index of greater than or equal to 0.3 L/min/m2
    • Time Frame: 6 hours post-removal of aortic X-clamp
  • Incidence of inotropes use according to protocol
    • Time Frame: 6 and 12 hours post-removal of aortic X-clamp
  • Peak and total release of Troponin
    • Time Frame: 6, 12 and 24 hours post-release of aortic X-clamp

Participating in This Clinical Trial

Inclusion Criteria

  • Adult – First-time – Isolated coronary artery bypass surgery Exclusion Criteria:

  • Diabetes Mellitus – Renal impairment with Creatinine greater than or equal to 200micromol/L – Atrial fibrillation – Amiodarone therapy, recent (in last month) or current – Hepatic impairment, significant preoperative – Peripheral neuropathy – Pregnancy or breast-feeding – Emergency surgery or required on clinical grounds within 5 days of referral

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital Birmingham
  • Collaborator
    • University of Birmingham
  • Provider of Information About this Clinical Study
    • Mr Domenico Pagano, University Hospital Birmingham
  • Overall Official(s)
    • Domeinco Pagano, MD FRCS, Principal Investigator, University Hospital Birmingham

References

Quinn DW, Pagano D, Bonser RS, Rooney SJ, Graham TR, Wilson IC, Keogh BE, Townend JN, Lewis ME, Nightingale P; Study Investigators. Improved myocardial protection during coronary artery surgery with glucose-insulin-potassium: a randomized controlled trial. J Thorac Cardiovasc Surg. 2006 Jan;131(1):34-42. doi: 10.1016/j.jtcvs.2005.05.057.

Ranasinghe AM, Quinn DW, Pagano D, Edwards N, Faroqui M, Graham TR, Keogh BE, Mascaro J, Riddington DW, Rooney SJ, Townend JN, Wilson IC, Bonser RS. Glucose-insulin-potassium and tri-iodothyronine individually improve hemodynamic performance and are associated with reduced troponin I release after on-pump coronary artery bypass grafting. Circulation. 2006 Jul 4;114(1 Suppl):I245-50. doi: 10.1161/CIRCULATIONAHA.105.000786.

Ashrafian H, Horowitz JD, Frenneaux MP. Perhexiline. Cardiovasc Drug Rev. 2007 Spring;25(1):76-97. doi: 10.1111/j.1527-3466.2007.00006.x.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.