In This SectionTexas Health Research & Education Institute
Disease or Condition
Effects of Once-Daily Oral Doses of 75mg Azimilide Dihydrochloride on the Incidence of Hospitalizations/Emergency Department or Cardiovascular Death in Patients with an Implantable Cardioverter Defibrillator
The purpose of this study is to see if a drug called azimilide, an investigational (experimental) new drug can help people with an ICD (defibrillator) have fewer cardiovascular (heart-related) emergency room visits and hospitalizations than participants not receiving azimilide. This study will compare azimilide with a placebo to see if taking azimilide is better than taking a placebo.
Men or women at least 18 years of age with a left ventricular ejection fraction (LVEF) = 40% as determined by echocardiography (ECHO), nuclear scan, left ventriculography, or cardiac magnetic resonance (CMR) imaging within 120 days prior to randomization.
Have an ICD implanted that meets the following criteria: (a) generates a biphasic waveform discharge; (b) tores intracardiac electrograms; (c) has both anti-tachycardia pacing and anti-bradycardia pacing capabilities; (d) has a minimum of 2 anti-tachycardia detecting zones and a ventricular fibrillation zone; and (e) has arrhythmia-discriminating algorithms (eg, high rate or sudden onset or rate stability).
Patients are eligible to participate in the study provided they meet one of the following 2 criteria: (a) patients who had their qualifying event before their first ICD implantation (“New ICD Patient”): must have had a documented episode of spontaneous sustained VT or VF (ventricular arrhythmia = 150 bpm lasting at least 30 seconds or requiring intervention during the sustained VT), or cardiac arrest, or VF during the 42 days preceding their first ICD implantation and be randomized during the 60 days immediately following their first ICD implantatio or (b) patients who had their qualifying event after their first ICD implantation or any subsequent re-implantation (“Existing ICD Patient”): must have had an ICD shock triggered by a spontaneous VT or VF after implantation and be randomized during the 180 days following this shock.
Patients who are eligible for the study must have their ICD programmed in the following manner: (a) Antitachycardia pacing must be programmed “on” for all patients at the time of randomization (see exception in 4[b]); (b) the device will be set for a minimum of 2 attempts of ATP in the lowest detection zone. Every attempt should be made to leave the ATP programmed “on” during the study unless, in the Investigator’s judgment, it is medically necessary to turn
ATP “off.” If ATP is turned “off,” the reason must be recorded on the eCRF; (c) the first shock will be delivered no lower than the lowest successful defibrillation energy at implantation or immediately before randomization; (d) programming of the ventricular tachycardia detection rate (the detection zone in which ATP will be given) should follow the parameters shown below, with adaptation dictated by the patient’s clinical condition and the Investigator’s
judgment: If The Slowest VT Rate Is The Floor Should Be The Ceiling Should Be = 150 bpm 10 bpm less than the VT rate 200 bpm 151 to 194 bpm 20 bpm less than the VT rate 200 bpm = 195 bpm or cardiac arrest with no documented VT rate Ventricular rate: 175 bpm 200 bpm, VT = ventricular tachycardia; (e) for dual chamber devices, at least 1 VT discriminator should be enabled (eg, for dual chamber devices, AV dissociation detection).
Women who meet one of the following: (a) women of childbearing potential with a negative serum pregnancy test at screening who are not breast feeding, do not plan to become pregnant during the study, and agree to use one or more approved methods of birth control during the study as judged to be appropriate by the Investigator. Approved methods of birth control are: oral, patch, injectable, or implantable hormonal contraception; intrauterine device; diaphragm plus spermicide; or female condom plus
spermicide. Abstinence, partner’s use of condoms, and partner’s vasectomy are not acceptable methods of contraception or (b) women who have been postmenopausal for at least 1 year (with amenorrhea for at least 1 year) or have had a hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation at least 6 months prior to signing the informed consent.
Have New York Heart Association (NYHA) Class IV CHF or have decompensated CHF at the time of randomization.
Have unstable angina pectoris or a myocardial infarction within 30 days of randomization.
Have a history of Torsade de Pointes or heart transplantation.
Have chronic atrial fibrillation or atrial fibrillation/flutter, that is not adequately rate-controlled in the judgment of the Investigator, at screening.
Have an electrocardiogram (ECG) with a QTc value > 460 msec (with a QRS = 120 msec), or a JTc value > 340 msec (with a QRS > 120 msec) (QT and JT intervals corrected by Bazett’s formula for heart rate) recorded during screening.
Have abnormalities (at screening) in the following clinical laboratory parameters: creatinine > 2.5 mg/dL (221 µmol/L); serum alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyltransferase = 3 · upper limit of normal (ULN), or bilirubin = 2 · ULN; potassium < 4.0 mEq or > 5.5 mEq, or magnesium below the lower limit of normal (potassium and magnesium levels can be adjusted back to normal range if judged by the Investigator, in consultation with the Study Medical Monitor, to be stabilized before randomization).
Have an absolute neutrophil count (ANC) < 1000/µL prior to randomization.
Are currently taking systemic Class I or other Class III antiarrhythmic drugs (must be off for = 5 dosing-intervals prior to randomization), including but not limited to quinidine, procainamide, disopyramide, systemic lidocaine, phenytoin, mexiletine, dofetilide, ibutilide, dronedarone, propafenone, moricizine, ranolazine, and sotalol; see exclusion criterion 11 regarding amiodarone.
Are currently taking systemic drugs that prolong the QT interval (must be off for 5 half-lives before dosing), including but not limited to clarithromycin, azithromycin, erythromycin, hydroxyzine, phenothiazines, and probucol.
Are currently taking or have taken immune-modulating drugs (eg, azathioprine, methotrexate, tumor necrosis factor alpha modifying drugs, or similar drugs which could affect the immune system or white blood cells) within 90 days before
Have taken oral amiodarone within 60 days before randomization or intravenous miodarone within 14 days before randomization; or if amiodarone treatment (oral or IV) was = 24 hours, have taken it within 5 days before randomization.
Use ticlopidine 30 days before randomization.
Have uncontrolled or untreated hypertension (systolic > 170 mm Hg, diastolic > 100 mm Hg). If a patient is receiving medical therapy for hypertension, his or her blood pressure should be stable for at least 1 week before randomization.
If female, are currently pregnant or breast feeding, or plan to become pregnant during the course of the study.
Have neoplasia, immune, infectious, or degenerative diseases that are likely to cause death or significant morbidity during the clinical study.
Have a systemic disease that, in the opinion of the Investigator, could impact compliance or study results.
Have qualifying ventricular fibrillation (episode that justified ICD implantation) during the acute phase (within 48 hours) of a myocardial infarction.
Are taking an investigational new drug, or have participated in any investigational study (with an approved or non-approved drug) within 30 days of randomization.
Have a non-approved ICD system (lead or generator): (a) have an ICD system (lead or generator) under current “recall” by the manufacturer; if a component of the ICD system is under “intensive monitoring” status by the manufacturer, the case should be discussed with the study’s medical monitor prior to randomization; (b) have an ICD pulse generator with a battery level of ERI (elective replacement indicator), EOL (end-of-life), or other indication of replacement need likely to occur in the 12 months following randomization.
Have a current diagnosis of psychosis.
Have known drug-induced organ toxicity.
Evidence of active hepatic disease, or any of the following: positive human immunodeficiency virus antibodies, positive hepatitis C antibody, positive hepatitis B surface antigen.
Use illicit drugs, or abuse alcohol (per Investigator’s judgment).
Are unwilling or unable to give or understand informed consent.