Myocardial Protection With Perhexiline in Left Ventricular Hypertrophy (HYPER)

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.

Study Overview

• Status: Unknown
• Conditions: Myocardial Reperfusion Injury; Hypertrophy, Left Ventricular; Cardiac Output, Low
• Intervention / Treatment: Drug: Perhexiline; Drug: Placebo marked PEXSIG

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Eshan Senanayake, MBBS MRCS; Phone Number: +44-7810-251454; Email: eshan.senanayake@uhb.nhs.uk
• Study Contact Backup: Name: Nigel E Drury, BM MRCS; Phone Number: +44-7714-332364; Email: nigel.drury@uhb.nhs.uk

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Recruiting
      • University Hospital Birmingham
      • Contact: Eshan Senanayake, MBBS MRCS; Phone Number: +44-7810-251454; Email: eshan.senanayake@uhb.nhs.uk
      • Contact: Nigel E Drury, BM MRCS; Phone Number: +44-7714-332364; Email: nigel.drury@uhb.nhs.uk
      • Principal Investigator: Domenico Pagano, MD FRCS
      • Sub-Investigator: Timothy R Graham, FRCS
      • Sub-Investigator: Stephen J Rooney, FRCS
      • Sub-Investigator: Ian C Wilson, MD FRCS
      • Sub-Investigator: C Jorge G Mascaro, MD FRCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital Birmingham
• Collaborators: Brighton and Sussex University Hospitals NHS Trust; British Heart Foundation; University of Birmingham
• Investigators: Principal Investigator: Domeinco Pagano, MD FRCS, University Hospital Birmingham

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Anticipated): September 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: October 2, 2009
• First Submitted That Met QC Criteria: October 2, 2009
• First Posted (Estimate): October 5, 2009

Study Record Updates

• Last Update Posted (Estimate): August 11, 2011
• Last Update Submitted That Met QC Criteria: August 10, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Aortic Valve Stenosis; Troponin; Perhexiline; Hypertrophy, Left Ventricular; Myocardial Reperfusion Injury; Cardiac Output, Low
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Pathological Conditions, Anatomical; Cardiomyopathies; Cardiomegaly; Hypertrophy; Reperfusion Injury; Myocardial Reperfusion Injury; Hypertrophy, Left Ventricular; Cardiac Output, Low; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Perhexiline
• Other Study ID Numbers: RRK3535; Eudract 2008-002376-95; REC 08/H0304/48; BHF PG/08/040