Ventricular arrhythmia in patients with implantable cardioverter-defibrillator (ICD) MedDRA version: 14.1 Level: PT Classification code 10047281 Term: Ventricular arrhythmia System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: Azimilide Dihydrochloride
Pharmaceutical Form: Tablet
INN or Proposed INN: AZIMILIDE
CAS Number: 149908-53-2
Other descriptive name: Azimilide dihydrochloride
Concentration unit: mg mill
Sponsors
Forest Research Institute, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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; 2. Have an ICD implanted that meets the following criteria: a. generates a biphasic waveform discharge; b. stores 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). 3. 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 OR 4. 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 5. 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 (VT = ventricular tachycardia): *If the slowest VT rate is = 150 bpm, then the floor should be 10 bpm less than the VT rate and the ceiling should be 200 bpm *If the slowest VT rate is 151 to 194 bpm, then the floor should be 20 bpm less than the VT rate and the ceiling should be 200 bpm *If the slowest VT rate is = 195 bpm or cardiac arrest with no documented VT rate, then the floor should be Ventricular rate: 175 bpm and the ceiling should be 200 bpm e. For dual chamber devices, at least 1 VT discriminator should be enabled (eg, for dual chamber devices, AV dissociation detection). 5. 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 metho
Exclusion criteria
Exclusion criteria: 1. Have New York Heart Association (NYHA) Class IV CHF or have decompensated CHF at the time of randomization; 2. Have unstable angina pectoris or a myocardial infarction within 30 days of randomization; 3. Have a history of Torsade de Pointes or heart transplantation; 4. Have chronic atrial fibrillation or atrial fibrillation/flutter, that is not adequately rate-controlled in the judgment of the Investigator, at screening; 5. 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; 6. 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 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); 7. Have an absolute neutrophil count (ANC) 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; 14. If female, are currently pregnant or breast feeding, or plan to become pregnant during the course of the study; 15. Have neoplasia, immune, infectious, or degenerative diseases that are likely to cause death or significant morbidity during the clinical study; 16. Have a systemic disease that, in the opinion of the Investigator, could impact compliance or study results; 17. Have qualifying ventricular fibrillation (episode that justified ICD implantation) during the acute phase (within 48 hours) of a myocardial infarction; 18. 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; 19. Have a non-approved ICD system (lead or generator); a. Have an ICD system (lead or generator) under c
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time-to-first all-cause shock; and Time-to-first unplanned physician-office visits that resulted in a change in therapy (reprogramming ICD or change in medication as it relates to ICD findings).;Timepoint(s) of evaluation of this end point: unplanned cardiovascular hospitalization, unplanned cardiovascular emergency room department visit, or cardiovascular death, unscheduled ICD-related physician office visit, or end of study, or withdrawal | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the impact of 75 mg azimilide versus placebo on the occurrence of unplanned (non-elective) cardiovascular hospitalizations, unplanned cardiovascular emergency department visits, or cardiovascular death in patients with an ICD. Analysis of efficacy will be done by comparing the effect of azimilide versus placebo on the time-to-first-occurrence of a qualifying event.;Secondary Objective: The secondary objectives of this study are to determine whether treatment with 75 mg azimilide versus placebo in patients with an ICD: • Reduces the occurrence of all-cause shocks, as assessed by prolonging time-to-first event; and • Reduces unplanned physician-office visits that resulted in a change in therapy (reprogramming ICD or change in medication as it relates to ICD findings), as assessed by prolonging time-to-first event.;Primary end point(s): The primary efficacy endpoint is the time-to-first-event of unplanned cardiovascular hospitalizations, unplanned cardiovascular emergency department visits, or cardiovascular death.;Timepoint(s) of evaluation of this end point: For the purposes of this study, cardiovascular events which trigger unplanned cardiovascular hospitalizations, unplanned cardiovascular emergency department visits are: • arrhythmias, • heart failure, • non-fatal cardiac arrest, • acute coronary syndrome, • cerebrovascular accident (except intracranial hemorrhage), • transient ischemic attack, • cardiovascular lightheadedness, • cardiovascular dizziness, • cardiovascular syncope, and • cardiovascular near-syncope. As part of the adjudication process, the CEC will classify cardiovascular events as arrhythmic or non-arrhythmic. | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Spain, Sweden, United States
Contacts
Public ContactMedpace Regulatory Submissions
Medpace Inc.
Outcome results
None listed