IRMA: Impact of Ranolazine in Blood Markers in Women With Angina and Metabolic Syndrome

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT02252406
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arms: 2
• Duration (Months): 44.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effects of ranolazine on different markers of cardiometabolic disease in women with stable angina.

Condition or Disease	Intervention/Treatment	Phase
Stable Angina; Metabolic Syndrome	Drug: Ranolazine; Other: Placebo	Phase 4

Detailed Description

Evaluate the ability of ranolazine to favorably modify thrombogenic, inflammatory, lipogenic, oxidative stress and hormonal biomarkers in a relatively short period of time in a group of ethnically diverse women with chronic stable angina and metabolic syndrome.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Impact of Ranolazine on Inflammatory, Thrombogenic, Lipogenic, Biomarkers in Women With Angina and Metabolic Syndrome.
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Dec 17, 2018
• Actual Study Completion Date: May 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranolazine Ranolazine would start with 500 mg BID and be force titrated to 1 gram po BID after 3 weeks. Down titration would only be allowed for side effects. This would be on top of all standard medical therapy.	Drug: Ranolazine; Ranolazine 500 mg from baseline to week 3 and 1000 mg thereafter until week 24; Other Names: Ranexa
Placebo Comparator: Placebo Placebo arm would start with 500 mg matching placebo tablet BID and be force titrated to 1 gram matching placebo tablet twice a day after 3 weeks. Down titration would only be allowed for side effects (if reported). This would be on top of all standard medical therapy.	Other: Placebo; Matching placebo tablets daily for 24 weeks.

Outcome Measures

Primary Outcome Measures

1. Impact of Ranolazine on Hemoglobin A1C [Change from baseline to 24 weeks]

   Will evaluate the impact of ranolazine in HgbA1C in women with Metabolic Syndrome (MBS)

2. Impact of Ranolazine on HDL-C Levels in Subjects [Change from Baseline to 24 weeks]

   Will evaluate the impact of ranolazine in HDL-C levels in women with metabolic syndrome

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with chronic stable angina (> 3 months) on evidence based adequate therapy

• Evidence of stable coronary artery disease by any of these:

• MI, PCI or CABG > 30 days prior to enrollment or

• Angiography showing > 50% stenosis in major vessel, branch or bypass graft > 30 days of enrollment or

• Abnormal stress MPI nuclear study, or DBA stress echo where the decision has been to treat medically and where angina has remained stable for >= 3 months

• Evidence of the Metabolic Syndrome: As defined by ATP III criteria i.e 3/5 of following Abdominal circumference F > 88 cm (35 in), M > 102 cm (40 in) Hypertriglyceridemia ≥ 150 mg/dl HDL F < 50 mg/dl M < 40 mg/dl Blood Pressure ≥130/85 Fasting Glucose ≥100 mg/dl For reproductive age women, a negative urine pregnancy test is required if all other inclusion criteria are met.

Exclusion Criteria:

• Exclusion of patients with contraindications to use of RANEXA, including patients on CYP3A4 inducers/potent inhibitors, and patients with liver cirrhosis.

• Exclusion of Patients with CrCl < 30 mL/min

• Limit dose of RANEXA to 500mg BID in patients on concurrent diltiazem/ verapamil

• Limit concurrent simvastatin to 20 mg/day

• Limit concurrent metformin to 1700 mg/day Additional Exclusion

• Patients with variable -inconsistent symptoms

• Patients with unstable coronary artery disease or revascularization within 30 days of enrollment.

• Patients who have known severe liver disease.

• Patients already receiving maximal ranolazine therapy for more than 4 weeks

• Presence of diabetes (AIC≥ 6.5 and /or on insulin therapy or anti-diabetic medication other than metformin) unstable hypothyroidism, active infection, active cancer (or ongoing chemotherapy and/or radiation within a year who are not on remission) and/or recent major surgery or illness.

• Patients with any contraindication to ranolazine see above

• Women of reproductive age are excluded if they are planning to become pregnant in the next 6 -12 months after randomization.

• Patients who are pregnant or lactating

• Documented allergic reaction to ranolazine in the past.

• Unexplained prolongation of the QTc > 500 milliseconds.

• Current or planned co-administration of moderate CYP3A inhibitors (eg, diltiazem, verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products) is not a full contraindication, if meet inclusion criteria otherwise, these patients could be accepted in trial but dose will be limited to 500 mg BID as stated previously.

• Current or planned co-administration of strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir) OR strong CYP3A inducers (eg, rifampin, rifabutin, rifapentine, phenobarbital, phenytoin,carbamazepine, and St. John's Wort) is a contraindication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Jacksonville	Florida	United States	32209

Sponsors and Collaborators

• University of Florida

Investigators

• Principal Investigator: Gladys P Velarde, MD, FACC, University of Florida

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 25, 2017

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02252406
• Other Study ID Numbers: WIRB20141202
• First Posted: Sep 30, 2014
• Last Update Posted: Apr 10, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Florida: Stable Angina; Metabolic Syndrome; Women; Biomarkers
• Additional relevant MeSH terms: Angina Pectoris; Angina, Stable; Metabolic Syndrome; Syndrome; Ranolazine

Study Results

Participant Flow

Recruitment Details	Recruitment period: 7/21/14 - 7/2/18 Location: UF Jacksonville Outpatient Cardiology clinic

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Ranolazine would start with 500 mg BID and be force titrated to 1 gram po BID after 3 weeks. Down titration would only be allowed for side effects. This would be on top of all standard medical therapy. Ranolazine: Ranolazine 500 mg from baseline to week 3 Ranolazine: Ranolazine 1000mg daily at week 3 until weeks 24.	Placebo arm would start with 500 mg matching placebo tablet BID and be force titrated to 1 gram matching placebo tablet twice a day after 3 weeks. Down titration would only be allowed for side effects (if reported). This would be on top of all standard medical therapy. Placebo: Matching placebo tablets daily for 24 weeks.
Period Title: Starting Dose Ranolazine 500 mg BID
STARTED	16	17
COMPLETED	12	14
NOT COMPLETED	4	3
Period Title: Starting Dose Ranolazine 500 mg BID
STARTED	12	14
COMPLETED	9	13
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Ranolazine	Placebo	Total
Arm/Group Description	Ranolazine would start with 500 mg BID and be force titrated to 1 gram po BID after 3 weeks. Down titration would only be allowed for side effects. This would be on top of all standard medical therapy. Ranolazine: Ranolazine 500 mg from baseline to week 3 Ranolazine: Ranolazine 1000mg daily at week 3 until weeks 24.	Placebo arm would start with 500 mg matching placebo tablet BID and be force titrated to 1 gram matching placebo tablet twice a day after 3 weeks. Down titration would only be allowed for side effects (if reported). This would be on top of all standard medical therapy. Placebo: Matching placebo tablets daily for 24 weeks.	Total of all reporting groups
Overall Participants	16	17	33
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 62.5%	10 58.8%	20 60.6%
>=65 years	6 37.5%	7 41.2%	13 39.4%
Sex: Female, Male (Count of Participants)
Female	16 100%	17 100%	33 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 5.9%	1 3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 12.5%	4 23.5%	6 18.2%
White	14 87.5%	12 70.6%	26 78.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	17 100%	33 100%

Outcome Measures

1. Primary Outcome

Title	Impact of Ranolazine on Hemoglobin A1C
Description	Will evaluate the impact of ranolazine in HgbA1C in women with Metabolic Syndrome (MBS)
Time Frame	Change from baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine Treated	Placebo
Arm/Group Description	We looked women randomized by table randomization to ranolazine that successfully titrated to maximum dose of tested drug (1,000 mg bid)	We looked women randomized by table randomization to placebo that successfully titrated to maximum dose of placebo drug
Measure Participants	9	13
Mean (Standard Deviation) [percent change]	-5 (6.2)	2.6 (9.1)

2. Primary Outcome

Title	Impact of Ranolazine on HDL-C Levels in Subjects
Description	Will evaluate the impact of ranolazine in HDL-C levels in women with metabolic syndrome
Time Frame	Change from Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine Treated	Placebo
Arm/Group Description	We looked women randomized by table randomization to ranolazine that successfully titrated to maximum dose of tested drug (1,000 mg bid)	We looked women randomized by table randomization to placebo that successfully titrated to maximum dose of placebo drug
Measure Participants	9	13
Mean (Standard Deviation) [percentage of change in HDL]	6.6 (15.7)	6.5 (46.6)

Adverse Events

Time Frame	Patients were followed for 24 weeks
Arm/Group Title	Ranolazine Treated		Placebo
Arm/Group Description	Ranolazine would start with 500 mg BID and be force titrated to 1 gram po BID after 3 weeks. Down titration would only be allowed for side effects. This would be on top of all standard medical therapy		Placebo arm would start with 500 mg matching placebo tablet BID and be force titrated to 1 gram matching placebo tablet twice a day after 3 weeks. Down titration would only be allowed for side effects (if reported). This would be on top of all standard medical therapy.
All Cause Mortality
	Ranolazine Treated		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/17 (0%)
Serious Adverse Events
	Ranolazine Treated		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Ranolazine Treated		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/16 (18.8%)		0/17 (0%)
Gastrointestinal disorders
upset stomach	3/16 (18.8%)	3	0/17 (0%)	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.