Steward Health Care System

Return to Results

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Ranolazine on Major Adverse Cardiovascular Events in Subjects With a History of Chronic Angina Who Undergo Percutaneous

new search

Trial Conditions
  • Coronary Artery Disease
  • Angina Pectoris
What is the purpose of this trial?

This study will evaluate the efficacy of ranolazine as compared with placebo when used as part of standard medical therapy in chronic angina subjects with incomplete revascularization post-PCI on the composite of ischemia-driven revascularization or ischemia-driven hospitalization without revascularization.

Date & Status

Recruiting

Who can Participate?

Eligibility

Ages:
18 and older

Gender:
Both

Eligibility

Inclusion Criteria

1. Written informed consent

2. Males and females aged 18 years and older

3. History of chronic angina defined as at least 2 episodes of anginal pain or
discomfort in the chest, jaw, shoulder, back, neck, or arm that is precipitated by
exertion or emotional stress, and relieved by rest or sublingual nitroglycerin, which
occurred on at least 2 separate days and at least 14 days prior to PCI (in the case
of staged PCI procedures, at least 14 days prior to the first PCI in the series).
Subjects may or may not have additional angina episodes within the 14 days prior to
their first PCI in the series, as well as anytime prior to Randomization.

4. PCI for any indication (ACS or non-ACS). For the purposes of stratification at
randomization, ACS will be defined as hospitalization for anginal pain or discomfort
within the previous 24 hours to their hospitalization with any one (or more) of the
following criteria:

i. Elevated troponin or creatinine kinase-MB (CK-MB) consistent with MI, as
reported by local laboratory and measured prior to index PCI ii.
Electrocardiographic changes (including transient changes) comprising new or
presumably new ST segment depression ≥ 0.1 mV (≥ 1 mm), or ST segment elevation ≥ 0.1
mV (≥ 1 mm) in at least 2 contiguous leads, or new or presumably new Left Bundle
Branch Block

5. Randomization within 14 days post-PCI. In the case of staged PCI procedures,
randomization has to occur within 14 days of the last PCI in the series. Subjects may
be randomized starting on the day of PCI and anytime during the following 14 days.
PCI is defined as an attempt to cross the lesion with a wire with the intention of
performing revascularization.

6. Post-PCI (post the last PCI for staged procedures) evidence of incomplete
revascularization defined as the presence of one or more visually estimated ≥ 50%
stenoses in one or more coronary arteries with reference vessel diameter of at least
2.0 mm, whether in the target vessel or in a non-target vessel regardless of the
presence or absence of coronary collaterals. In the case of a subject post-CABG,
incomplete revascularization is defined as the presence of one or more visually
estimated ≥ 50% stenoses in an unbypassed epicardial vessel with a reference diameter
of ≥ 2.0 mm, or one or more visually estimated ≥ 50% stenoses in a bypass graft
supplying an otherwise unrevascularized myocardial territory.

7. Clinically stable post-PCI. Subjects randomized in-hospital on day of planned
discharge or in clinic are considered stable. Subjects randomized in-hospital prior
to day of planned discharge must meet all of the following criteria:

i. CK-MB < 3 times the upper limit of normal (ULN) at least 3 hours post-PCI, or if ≥
3 times the ULN with evidence of decreasing CK-MB (decreased by at least 20% from the
prior measurement) as reported by local laboratory. If CK-MB is not available, a
subject must have evidence of normal or decreasing troponin levels (by at least 20%
from the prior measurement) at least 3 hours post-PCI, as reported by local
laboratory.

ii. Systolic blood pressure ≥ 90 mm Hg and not receiving pressors or inotropes iii.
No current requirement for an intra-aortic balloon pump (IABP) or any left
ventricular assist device iv. No current requirement for intravenous (IV)
nitroglycerin

8. Ability and willingness to comply with all study procedures during the course of the
study

9. Females of childbearing potential must have a negative pregnancy test at Screening
(unless surgically sterile or post menopausal) and must agree to use highly effective
contraception methods from Screening throughout the duration of study treatment and
for 14 days following the last dose of study drug.

Exclusion Criteria

1. Any future planned revascularization (including staged procedures) or possible
planned revascularization (ie, planned stress test to assess the imminent need for
additional revascularization). Future planned stress tests for purposes of monitoring
are permitted but strongly discouraged. Subjects may be enrolled after the last PCI
in the staged series or once a decision is made not to perform a follow up PCI, as
long as Randomization occurs within 14 days from the last PCI. If a subject has had a
stress test post-PCI and prior to Randomization and no further intervention is
planned, the subject may be enrolled within 14 days from the last PCI.

2. Unrevascularized left main coronary artery stenosis ≥ 50%. Subjects with a history of
CABG to the left coronary system will be considered to have a revascularized left
main if at least one graft is patent.

3. Major complication during or after the index PCI (in the case of staged PCI, the last
in the series) including:

i. Major bleeding (TIMI Bleeding classification or any bleeding requiring blood
transfusion of ≥ 2 units of red blood cells) ii. Coronary perforation requiring
treatment iii. Procedural complication requiring surgery (including CABG or
peripheral vascular surgery)

4. Stroke within 90 days prior to Randomization, or any history of stroke with permanent
major neurologic disability (eg, aphasia or significant motor dysfunction)

5. Cardiogenic shock within 90 days prior to Randomization (transient decreases in blood
pressure without clinical sequelae are not considered to be cardiogenic shock)

6. New York Heart Association (NYHA) Class III or IV heart failure

7. Severe renal insufficiency as assessed by an estimated GFR < 30 mL/min/1.73m2 using
the 4 variable modification of diet in renal disease (MDRD) equation per local
laboratory (based on the last available measurement prior to Randomization, collected
within 1 month prior to the index PCI [in the case of staged PCI, the last in the
series])

8. Liver cirrhosis

9. Use of Class Ia, Ic, or Class III antiarrhythmics, except for amiodarone

10. Current treatment with strong inhibitors of CYP3A

11. Current treatment with CYP3A4 inducers or P-gp inducers

12. Subjects taking > 20 mg simvastatin daily or > 40 mg lovastatin daily who cannot
reduce the dose to 20 mg once daily for simvastatin or 40 mg once daily for
lovastatin, or who cannot switch to another statin

13. Subjects taking greater than a total of 1000 mg daily of metformin who cannot reduce
the dose to a maximum total of 1000 mg daily (additional anti-diabetic medications
may be added as clinically indicated to allow subjects to decrease their metformin
dose and maintain glycemic control)

14. Previous treatment with ranolazine for > 7 consecutive days within 30 days prior to
Randomization, or known hypersensitivity or intolerance to ranolazine or to any of
the excipients

15. Participation in another investigational drug or investigational device study within
30 days prior to Randomization (participation in registries is allowed)

16. Women who are pregnant or breast feeding

17. Non-CAD comorbid conditions (eg, advanced malignancy, severe aortic stenosis) which
are likely to result in death within 2 years of Randomization

18. Any condition that in the opinion of the investigator would preclude compliance with
the study protocol

Gender: Both
Steward Physician(s)
  • Ramin Farzaneh-Far, MD, FACC
Trial Interventions
Drug
  • Ranolazine
  • Placebo
Physician Researcher

Investigator Name:

  • Ramin Farzaneh-Far, MD, FACC

Other Information

Sponsor: Gilead Sciences
Phase: Phase 3
Trial ID: NCT01442038
Volunteers:  Not Accepting Healthy Volunteers

new search

Connect with Steward

Visit Our Twitter Feed Visit Our Facebook Page Email This Page Print This Page

Subscribe to our patient e-newsletter

Copyright © 2014 Steward Health Care
Connect Healthcare Panacea CMS Solutions