Ranolazine Cardioprotection in PCI

• Sponsor: Harvey Hahn (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01767987
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 6
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The investigators will test if upfront dosing of Ranolazine can reduce myocardial biomarker release (CK-MB, Troponin) post percutaneous coronary intervention (PCI).

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Ranolazine; Drug: Placebo	Phase 2

Detailed Description

Ranolazine has been demonstrated to decrease angina, ischemia on perfusion imaging, improve diastolic function, and cardiac metabolism. Furthermore it has been associated with reduced cardiac arrhythmias, including non-sustained ventricular tachycardia and atrial fibrillation. It has not been studied as an acute cardioprotective agent in percutaneous coronary intervention (PCI).

We hypothesize that upfront administration of Ranolazine could decrease the myocardial injury associated with PCI due to all the factors listed above (i.e. precondition the myocardium). We plan to screen all patients scheduled for an elective coronary angiogram. Those who meet criteria and consent will be randomized to either receive Ranolazine or placebo twice a day for 3 days leading up to the PCI.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Ranolazine Cardioprotection in PCI
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ranolazine Oral treatment Intervention: Drug: Ranolazine 1000 mg	Drug: Ranolazine; Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI; Other Names: Ranexa
Placebo Comparator: Placebo Oral treatment Intervention: Drug: Placebo	Drug: Placebo; Drug: Placebo Oral dose twice per day for 3 days leading up to PCI

Outcome Measures

Primary Outcome Measures

1. Troponin [8-10 hrs post PCI]

   Troponin labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first

2. CK-MB [8-10 hrs post PCI]

   CK-MB labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first

Secondary Outcome Measures

1. TIMI Flow Rate (Grade) [TIMI Flow Rate (Grade) is assessed immediately after an interventional reperfusion attempt during a PCI (Percutaneous Coronary Intervention) procedure.]

   This TIMI classification was developed by the TIMI (Thrombolysis In Myocardial Infarction) study group to semiquantitatively assess coronary artery perfusion beyond point of occlusion on coronary angiography.* TIMI Grade [Description] TIMI 0 - no perfusion [no antegrade flow beyond the point of occlusion] TIMI 1 - penetration without perfusion [faint antegrade coronary flow beyond the occlusion with incomplete filling of the distal coronary bed] TIMI 2 - partial perfusion [delayed or sluggish antegrade flow with complete filling of the distal territory] TIMI 3 - complete perfusion [normal flow with complete filling of the distal territory] *(see http://radclass.mudr.org/content/timi-grade-flow-grading-coronary-blood-flow-during-coronary-angiography) TIMI 0 is the least favorable grade. TIMI 3 is the most favorable grade.

2. Incidence of Atrial Fibrillation, Ventricular Tachycardia, or Ventricular Fibrillation in Coronary Cath Lab [During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire]

   Abnormal heart activity

3. Incidence of Non-sustained Ventricular Tachycardia or Atrial Fibrillation Post PCI [Following completion of PCI through hospital discharge]

4. Left Ventricular End Diastolic Pressure (LVEDP) [During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire]

5. Death, Myocardial Infarction (Biomarker Greater Than 2x Normal), CHF, Cardiac Arrest [At discharge or within 1 days, whichever comes first]

6. Death, MI, Revascularization, CHF [1-4 weeks post PCI]

7. Successful PCI [At discharge or within 1 days, whichever comes first]

   For the purposes of this study, a successful PCI is considered one where no additional coronary interventions were required within 24 hours after the initial PCI.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 or older

• Patients undergoing Coronary Angiography with possible PCI

• Able and willing to give consent

• Able to read and write English

Exclusion Criteria:

• Current EKG or Biomarker of Acute Myocardial Infarction (MI) or Acute Coronary Syndromes (ACS)

• History of Allergy to Ranolazine

• Pregnant or Nursing

• Currently taking Ranolazine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kettering Medical Center	Kettering	Ohio	United States	45429

Sponsors and Collaborators

• Harvey Hahn
• Gilead Sciences

Investigators

• Principal Investigator: Harvey S Hahn, MD, Kettering Health Network

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Harvey Hahn, Director, Cardiovascular Fellowship Training Program and Director, Cardiac Noninvasive Laboratory, Kettering Health Network
• ClinicalTrials.gov Identifier: NCT01767987
• Other Study ID Numbers: ISR IN-US-259-0139
• First Posted: Jan 15, 2013
• Last Update Posted: Sep 14, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Harvey Hahn, Director, Cardiovascular Fellowship Training Program and Director, Cardiac Noninvasive Laboratory, Kettering Health Network: Acute Coronary Syndrome; ACS; Percutaneous Coronary Intervention; PCI; Ranolazine; Coronary Angiogram; Cardioprotectant
• Additional relevant MeSH terms: Acute Coronary Syndrome; Ranolazine

Study Results

Participant Flow

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Period Title: Overall Study
STARTED	4	2
COMPLETED	0	1
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Ranolazine	Placebo	Total
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI	Total of all reporting groups
Overall Participants	4	2	6
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61.5	67.5	63.5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 50%	0 0%	2 33.3%
>=65 years	2 50%	2 100%	4 66.7%
Sex: Female, Male (Count of Participants)
Female	3 75%	1 50%	4 66.7%
Male	1 25%	1 50%	2 33.3%
Region of Enrollment (participants) [Number]
United States	4 100%	2 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Troponin
Description	Troponin labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first
Time Frame	8-10 hrs post PCI

Outcome Measure Data

Analysis Population Description

Of the 4 Ranolazine Group subjects, 1 was withdrawn for pre-procedure study drug non-compliance; 3 had no PCI intervention. Of the 2 Placebo Group subject, 1 had no PCI intervention. The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject undergoing this protocol required test.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [NG/ML]	0.023

2. Primary Outcome

Title	CK-MB
Description	CK-MB labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first
Time Frame	8-10 hrs post PCI

Outcome Measure Data

Analysis Population Description

For the single subject completing the PCI intervention, CK-MB was not done because the CK level was below the threshold running the CK-MB test.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	0

3. Secondary Outcome

Title	TIMI Flow Rate (Grade)
Description	This TIMI classification was developed by the TIMI (Thrombolysis In Myocardial Infarction) study group to semiquantitatively assess coronary artery perfusion beyond point of occlusion on coronary angiography.* TIMI Grade [Description] TIMI 0 - no perfusion [no antegrade flow beyond the point of occlusion] TIMI 1 - penetration without perfusion [faint antegrade coronary flow beyond the occlusion with incomplete filling of the distal coronary bed] TIMI 2 - partial perfusion [delayed or sluggish antegrade flow with complete filling of the distal territory] TIMI 3 - complete perfusion [normal flow with complete filling of the distal territory] *(see http://radclass.mudr.org/content/timi-grade-flow-grading-coronary-blood-flow-during-coronary-angiography) TIMI 0 is the least favorable grade. TIMI 3 is the most favorable grade.
Time Frame	TIMI Flow Rate (Grade) is assessed immediately after an interventional reperfusion attempt during a PCI (Percutaneous Coronary Intervention) procedure.

Outcome Measure Data

Analysis Population Description

The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom this protocol required data point was collected.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [units on a scale]	3

4. Secondary Outcome

Title	Incidence of Atrial Fibrillation, Ventricular Tachycardia, or Ventricular Fibrillation in Coronary Cath Lab
Description	Abnormal heart activity
Time Frame	During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire

Outcome Measure Data

Analysis Population Description

The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [participants]	0 0%

5. Secondary Outcome

Title	Incidence of Non-sustained Ventricular Tachycardia or Atrial Fibrillation Post PCI
Time Frame	Following completion of PCI through hospital discharge

Outcome Measure Data

Analysis Population Description

The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [participants]	0 0%

6. Secondary Outcome

Title	Left Ventricular End Diastolic Pressure (LVEDP)
Time Frame	During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire

Outcome Measure Data

Analysis Population Description

The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom this protocol required data point was collected.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [mmHG]	10

7. Secondary Outcome

Title	Death, Myocardial Infarction (Biomarker Greater Than 2x Normal), CHF, Cardiac Arrest
Time Frame	At discharge or within 1 days, whichever comes first

Outcome Measure Data

Analysis Population Description

The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [participants]	0 0%

8. Secondary Outcome

Title	Death, MI, Revascularization, CHF
Time Frame	1-4 weeks post PCI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [participants]	0 0%

9. Secondary Outcome

Title	Successful PCI
Description	For the purposes of this study, a successful PCI is considered one where no additional coronary interventions were required within 24 hours after the initial PCI.
Time Frame	At discharge or within 1 days, whichever comes first

Outcome Measure Data

Analysis Population Description

The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI	Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
Measure Participants	0	1
Number [participants]	1 25%

Adverse Events

Time Frame	Adverse event data was collected from time of consent through end of study discharge from hospital. Adverse events unresolved at discharge were to be followed to resolution. No events occuring after discharge were to be recorded as adverse events.
Adverse Event Reporting Description	Study timeline consisted of consent, pre-procedure medication (3 days), arrival for out-patient heart cath procedure, possible PCI, post-procedure recovery time, and discharge from hospital recovery room. Time from consent to start of study meds varied. Time from start of study drug to discharge was 4 days.
Arm/Group Title	Ranolazine		Placebo
Arm/Group Description	Oral treatment Intervention: Drug: Ranolazine 1000 mg Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI		Oral treatment Intervention: Drug: Placebo Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
All Cause Mortality
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.