Myocardial Protection With Perhexiline in Left Ventricular Hypertrophy

Study Overview
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Brief Summary
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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. Patients with a thickened wall of the heart (left ventricular hypertrophy) may be at greater risk. 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.

Official Title
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Myocardial Protection With Perhexiline in Left Ventricular Hypertrophy

Conditions
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Myocardial Reperfusion Injury, Cardiac Output, Low, Hypertrophy, Left Ventricular

Intervention / Treatment
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* Drug: Perhexiline
* Drug: Placebo marked PEXSIG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult First-time Aortic valve surgery for aortic stenosis +/- coronary artery bypass 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perhexiline<br>Pre-operative administration of Perhexiline tablets according to dosing schedule | Drug: Perhexiline<br>* Tablets. Dose: 200mg BD for 3 days, then 100mg BD until surgery. Duration of therapy: 5-31 days.<br>* Other names: PEXSIG;|
| Placebo Comparator: Placebo marked PEXSIG<br>Pre-operative administration of placebo tablets according to dosing schedule | Drug: Placebo marked PEXSIG<br>* Tablets. Dose: 200mg BD for 3 days, then 100mg BD until surgery. Duration of therapy: 5-31 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute difference in Cardiac Index (>0.3 l/min/m2) |  | 6 hours post-removal of aortic X-clamp | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Low Cardiac Output Syndrome |  | 6 hours post-removal of aortic X-clamp | 
| Incidence of inotrope use according to protocol |  | 6 and 12 hours post-removal of aortic X-clamp | 
| Peak and total release of Troponin |  | 12 and 24 hours post-release of aortic X-clamp | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perhexiline, Aortic Valve Stenosis, Hypertrophy, Left Ventricular, Myocardial Reperfusion Injury, Cardiac Output, Low, Troponin