Catecholamine-O-Methyl-Transferase(COMT)-Polymorphism in Cardiac Surgery

NCT00334009 | Completed

• 1 other identifier: H2005/02320
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Although clinical risk factors for postoperative development of vasodilatory shock and acute renal failure have been identified; there is a considerable proportion of patients undergoing cardiac surgery where this syndrome cannot be predicted. We sought to investigate the impact of Catecholamine-O-Methyltransferase (COMT) polymorphism on the duration of vasodilatory shock and other important clinical outcomes in cardiac surgery patients. COMT is a key enzyme in the degradation of catechols eg. catecholamines. 25% of the population have a low activity (L/L) of this enzyme. Sustained low COMT activity is associated with an altered metabolic profile of catecholamines and their degradation products. The process of cardiopulmonary bypass (CPB)over-activates some of the same mechanisms the body uses to defend itself against severe infection. One of the main overactive defence mechanisms is the release of highly toxic compounds derived from oxygen - a process called 'oxidative-stress'. Increased reactive oxygen species (ROS) generation can lead to inactivation of biologic mediators, including catecholamines. It is well established that some radicals autoxidizes catecholamines, including DA, NE, and epinephrine and contribute significantly to vasoplegia. As part of this study, we will take six 2.7mL samples of blood, collected before, and after the operation, from the arterial catheter routinely inserted in every patient. This blood will be used to measure COMT genotype, the concentration of plasma-catecholamines as well as marker of oxidative stress. Our plan is to enrol patients undergoing cardiac surgery if the use of the CPB is planned.

Conditions

Cardiac Surgery

Keywords

Cardiac Surgery; Cardiopulmonary Bypass; COMT-Polymorphism; Vasoplegia; Catecholamines; Acute Renal Failure

Outcome Measures

Primary Outcomes (1)

• duration of vasoplegia and incidence of acute renal failure following cardiopulmonary bypass

Secondary Outcomes (1)

• length of stay in intensive care and in hospital, requirement of renal replacement therapy, mortality

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing elective cardiac surgery (in whom CPB is planned) at the Austin Hospital and Warringal Private Hospital.

You may not qualify if:

• Intake of Levodopa
• Intake of COMT inhibitors (e.g. Entacapone, Tolcapone)
• Intake of monoamino oxidase inhibitors type A and B (e.g. Moclobemide, Selegiline, Rasagiline)
• Patients below 18 years of age
• oral steroids
• emergency patients (cardiac symptoms occurred \< 24 hours prior to operation)
• patients receiving IV nitrates/nitroprusside sodium

Sponsors & Collaborators

• Austin Health: lead

Study Sites (1)

Austin Hospital

Melbourne, Victoria, 3084, Australia

Location

Related Publications (1)

• Haase-Fielitz A, Haase M, Bellomo R, Lambert G, Matalanis G, Story D, Doolan L, Buxton B, Gutteridge G, Luft FC, Schunck WH, Dragun D. Decreased catecholamine degradation associates with shock and kidney injury after cardiac surgery. J Am Soc Nephrol. 2009 Jun;20(6):1393-403. doi: 10.1681/ASN.2008080915. Epub 2009 Apr 30.

  PMID: 19406978 DERIVED

MeSH Terms

Conditions

Vasoplegia; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Rinaldo Bellomo, MD, FRACP

  Austin Health

  PRINCIPAL INVESTIGATOR

• Duska Dragun, MD

  Department of Nephrology, Charite University Hospital, Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: June 5, 2006
• First Posted: June 6, 2006
• Study Start: June 1, 2006
• Study Completion: November 1, 2006
• Last Updated: March 6, 2008

Record last verified: 2008-03

Locations

AU (1)