Trial Outcomes & Findings for Ranolazine Implantable Cardioverter-Defibrillator Trial (NCT NCT01215253)

NCT ID: NCT01215253

Last Updated: 2018-08-27

Results Overview

Primary endpoint of the study will be defined as a composite endpoint consisting of Ventricular Tachycardia or Ventricular Fibrillation requiring antitachycardia pacing (ATP) therapy, implantable cardioverter-defibrillator (ICD) shock, or death, whichever occurs first.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1012 participants
• Primary outcome timeframe: 2 years of follow-up on average
• Results posted on: 2018-08-27

Participant Flow

1012 patients were recruited from 88 centers in the US and 7 centers in Canada

Participant milestones

Measure	Ranolazine At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Overall Study STARTED	510	502
Overall Study COMPLETED	424	439
Overall Study NOT COMPLETED	86	63

Reasons for withdrawal

Measure	Ranolazine At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Overall Study Withdrawal by Subject	57	35
Overall Study Physician Decision	9	12
Overall Study Lost to Follow-up	6	4
Overall Study Other	14	12

Baseline Characteristics

Ranolazine Implantable Cardioverter-Defibrillator Trial

Baseline characteristics by cohort

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Total n=1012 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 10.3 • n=5 Participants	64.2 years STANDARD_DEVIATION 9.9 • n=7 Participants	64.3 years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	100 Participants n=5 Participants	86 Participants n=7 Participants	186 Participants n=5 Participants
Sex: Female, Male Male	410 Participants n=5 Participants	416 Participants n=7 Participants	826 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	12 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	493 Participants n=5 Participants	490 Participants n=7 Participants	983 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	85 Participants n=5 Participants	85 Participants n=7 Participants	170 Participants n=5 Participants
Race (NIH/OMB) White	404 Participants n=5 Participants	410 Participants n=7 Participants	814 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Canada	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Region of Enrollment United States	479 Participants n=5 Participants	471 Participants n=7 Participants	950 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Primary endpoint of the study will be defined as a composite endpoint consisting of Ventricular Tachycardia or Ventricular Fibrillation requiring antitachycardia pacing (ATP) therapy, implantable cardioverter-defibrillator (ICD) shock, or death, whichever occurs first.

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Patients With Ventricular Tachycardia (VT) or Ventricular Fibrillation (VF) or Death	174 Participants	198 Participants

SECONDARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Implantable cardioverter-defibrillator (ICD) shock for VT or VF or death, whichever occurs first.

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Patients With VT or VF Requiring ICD Shock or Death	131 Participants	145 Participants

SECONDARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Total number of recurrent ICD therapies requiring antitachycardia pacing (ATP) or shock will be analyzed, not just first event

Outcome measures

Measure	Ranolazine n=741 VT/VF events At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=986 VT/VF events Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Recurrent Episodes of VT or VF Requiring Antitachycardia Pacing (ATP) or ICD Shock Therapies	433 VT/VF events	650 VT/VF events

SECONDARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Number of patients with first inappropriate ICD shock for other reasons than VT or VF

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Patients With First Inappropriate ICD Shock	16 Participants	20 Participants

SECONDARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Number of patients with a composite endpoint of cardiovascular hospitalization or death, whichever occurred first.

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Patients With Hospitalization for Cardiac Causes or Death, Whichever Occurred First.	237 Participants	222 Participants

SECONDARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Number of patients with a composite endpoint of heart failure hospitalization or death, whichever occurred first.

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Patients With Heart Failure Hospitalization or Death, Whichever Occurred First	144 Participants	140 Participants

SECONDARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Death as a safety endpoint of the trial

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Death	70 Participants	78 Participants

SECONDARY outcome

Timeframe: 1 year of follow-up

Population: Data was not collected on 86 patients in the placebo arm and 99 patients in the Ranolazine arm.

Exercise capacity measured by the 6-minute walk test

Outcome measures

Measure	Ranolazine n=325 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=353 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Mean Meters Walked in 6 Minutes	314 meters Standard Deviation 127.5	309 meters Standard Deviation 123.5

SECONDARY outcome

Timeframe: 1 year follow-up

Population: Data was not collected in 42 patients in the placebo arm and 61 patients in the Ranolazine arm.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a new, self-administered, 23-item questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. The scale ranges from 0-100 with lower scores indicating worse outcomes.

Outcome measures

Measure	Ranolazine n=363 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=397 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Quality of Life Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)	73.6 units on a scale Standard Deviation 24.1	72.8 units on a scale Standard Deviation 24.3

SECONDARY outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Number of recurrent inappropriate ICD shocks in all patients combined.

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Recurrent Inappropriate ICD Shocks	19 events	26 events

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

Number of patients whose first VT or VF required antitachycardia pacing (ATP)

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Patients Whose First VT/VF Required Antitachycardia Pacing (ATP)	92 Participants	117 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years of follow-up on average

Population: This outcome measure was an intent-to-treat analysis therefore all randomized subjects were included.

number of patients whose first VT or VF required ICD shock

Outcome measures

Measure	Ranolazine n=510 Participants At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 Participants Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Number of Patients Whose First VT/VF Required ICD Shock	79 Participants	84 Participants

Adverse Events

Ranolazine

Serious events: 0 serious events

Other events: 69 other events

Deaths: 70 deaths

Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 78 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ranolazine n=510 participants at risk At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl \<60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if \<30ml/min. For patients with CrCl \<60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if \<30ml/min. Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.	Placebo n=502 participants at risk Ranolazine: At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
General disorders dizziness	7.6% 39/510 • approximately 2 years (median 27 months).	2.2% 11/502 • approximately 2 years (median 27 months).
Gastrointestinal disorders nausea	5.9% 30/510 • approximately 2 years (median 27 months).	1.2% 6/502 • approximately 2 years (median 27 months).

Additional Information

Wojciech Zareba

University of Rochester

Phone: 585-275-5391

Email: wojciech.zareba@heart.rochester.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place