Progress Report - June 2007

The clozapine study now has 67 patients in the database including:

No troponin rise in 2 cases

Two of the cases had no documented rise in troponin I.  For one of these, troponin I was checked daily from when the patient became ill, so if a rise occurred it would have been detected.  This case was confirmed by increase in heart rate and deterioration in left ventricular function documented by echocardiogram (compared with baseline).

The second case was fatal without apparent warning.  The next weekly blood sample was to be taken the day of the death.  The sample taken after cardiac arrest showed no rise in troponin I.  The case was diagnosed by cardiac histology which the pathologist determined was characteristic of hypersensitivity myocarditis with clozapine being the most likely cause.

Access to blood and tissue samples of deceased individuals

It has been possible to ascertain that blood or tissue samples are available from at least 10 individuals who have died of clozapine-related myocarditis.  In relation to 3 of these cases, an ethics committee application has been submitted to the Victorian Institute of Forensic Medicine.  An application will soon be made to the ethics committee at Royal Prince Alfred Hospital, Sydney South West Area Health Service in relation to the other seven.

DNA will be extracted from these samples for genetic analysis.  Those who have died have developed a particularly severe form of myocarditis.  Obtaining DNA from this group may be critical to the success of the genetic analysis, since the genetic signal may be clearer or sharper.

Ethics applications

Approvals have now been obtained from 8 site-related ethics committees, covering a total of 15 hospitals.  The approvals are listed on the main web page.

Contact has been made with other centres and support for the study has been received from psychiatrists around Australia.  Further ethics applications will be submitted shortly.