Angina PectorisPhase 4TERISANCT01425359
Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina
A Phase 4 study testing Ranolazine in people with Angina Pectoris and Coronary Artery Disease, run by Gilead Sciences at 135 sites in 14 countries.
Trial summary
This study will evaluate the effect of ranolazine compared to placebo on the average weekly angina frequency in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM), and whether ranolazine can reduce the frequency of angina (chest pain) attacks… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Angina Pectoris, Coronary Artery Disease, Type 2 Diabetes Mellitus
- What is being tested?
- Ranolazine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 949 participants
- Where
- 135 sitesin 14 countries
- Study dates
- Sep 2011to Oct 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Males and females aged at least 18 years
- At least a 3-month history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin
- CAD documented by one or more of the following:
- Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries
- History of myocardial infarction (MI) documented by positive myocardial muscle creatine kinase (CK-MB) enzymes, troponins, or electrocardiogram (ECG) changes
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- Cardiac imaging study or exercise test diagnostic for CAD
- Treatment with up to 2 antianginal therapies at a stable dose for at least 2 weeks prior to the Qualifying Period.
- Documented history of T2DM
- Willing to maintain stable tobacco usage habits throughout the study
- Willing to maintain stable activity levels throughout the study
- Females of childbearing potential must agree to utilize highly effective contraception methods from Screening throughout the duration of study treatment and for 14 days following the last dose of study drug.
Who cannot join
- New York Heart Association (NYHA) Class III and IV
- Acute coronary syndrome in the prior 2 months or planned coronary revascularization during the study period
- Stroke or transient ischemic attack within 6 months prior to Screening
- QTc > 500 milliseconds
- Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg)
- Systolic blood pressure < 100 mmHg
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- Clinically significant hepatic impairment
- Prior treatment with ranolazine, or known hypersensitivity or intolerance to ranolazine
- Females who are breastfeeding
- Positive serum pregnancy test
- Participation in another investigational drug or device study within 1 month prior to Screening
- Current treatment with trimetazidine, ivabradine, or nicorandil. Subjects will need to discontinue these medications 2 weeks prior to the Qualifying Period.
- Current treatment with potent inhibitors of cytochrome (CYP)3A (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
- Current treatment with CYP3A and P glycoprotein (Pgp) inducers (eg, rifampicin/rifampin, carbamazepine, and St. John's wort [Hypericum perforatum])
- Current treatment with CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, and sirolimus)
- Subjects taking simvastatin who cannot reduce the dose to 20 mg once daily or who cannot switch to another statin
- Current treatment with Class I or III antiarrhythmic medications
- History of illicit drug use or alcohol abuse within 1 year of Screening
- Any other conditions that, in the opinion of the investigator, are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study
Trial locations and contacts
135 sites in 14 countries.
135 sites in 14 countries
Russia37 sites
Altay Regional Cardiologycal Dispensary
Barnaul, 656055
"Chita State Medical Academy" Curative-Diagnostic Clinic department
Chita, 672039
Municipal Institution of Healthcare "Kemerovo Cardiology Dispensary"
Kemerovo, 650002
Non-state Institution of healthcare "Department hospital on station Kemerovo of OAO "Russian Railway"
Kemerovo, 650056
Medical centre "Delis", LLC
Kirovsk, 187342
Federal State Institution "National Research Center for Preventive Medicine"
Moscow, 101990
State healthcare institution of Moscow "City Clinical hospital#15 named after O.M.Filatov"
Moscow, 111539
State Healthcare institution of Moscow"Cardiology Dispensary #2"
Moscow, 117556
First Moscow State Medical University I.M. Sechenov
Moscow, 119991
State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department
Moscow, 119991
State Budget Educational Institution of High Professional Education First Moscow State Medical University... #1, Cardiology Clinic, Hospital Therapy Department
Moscow, 119992
Moscow City Clinical Hospital #51
Moscow, 121309
FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF
Moscow, 121359
Moscow State University of Medicine and Dentistry based on Moscow City Clinical Hospital #71
Moscow, 121374
City Clinical Hospital named after S.P.Botkin
Moscow, 125284
State Institution of Moscow Healthcare "City Clinical Hospital named after S.P. Botkin"
Moscow, 125284
Moscow State Institution of Health "City Clinical Hospital #81"
Moscow, 127644
Federal State Institution "Outpatient department #3" of President Management department of Russian Federation
Moscow, 129090
State Novosibirsk Regional Clinical Hospital
Novosibirsk, 630087
Regional Clinical Hospital named after N.N.Burdenko
Penza, 440026
State Institution of Healthcare Perm Regional Hospital for War Veterans
Perm, 614097
City Hospital #38 named after Semashko N.A
Pushkin, Sankt-Peterburg, 196601
State Healthcare Institution "Ryazan regional clinical cardiological dispensary"
Ryazan, 390026
FGU Central Clinical Hospital with Polyclinic of President Administrative Department of RF
Saint Petersburg, 121359
Federal State Educational Institution of High Professional Education "Military Medical Academy n.a. S.M. Kirov" of the Ministry of Defence of Russia
Saint Petersburg, 191124
International Medical Center "SOGAZ", LLC
Saint Petersburg, 191186
State Healthcare institution "Municipal Out-patient Clinic #109"
Saint Petersburg, 192288
Saint-Petersburg State Healthcare Institution
Saint Petersburg, 193144
Federal Heart, Blood and Endocrinology Centre n.a. Almazov
Saint Petersburg, 194156
Institution and Address: "Medical Research Institute", LLC
Saint Petersburg, 196084
Federal Heart, Blood and Endocrinology Centre n.a. Almazov
Saint Petersburg, 197341
State Institution of Healthcare "City Hospital #40 of Kurortniy administrative district
Saint Petersburg, 197705
"Clinical hospital named after S.R.Mirotvortsev"
Saratov, 410054
Educational Institution of Higher Vocational Education "Smolensk State Medical Academy" on the base of Municipal Medicoprophylactic Institution "Hospital of Emergency Medical Care",
Smolensk, 214000
Autonomous healthcare institution of Voronezh region "Voronezh regional clinic consultative and diagnostic centre"
Voronezh, 394018
Municipal Institution of Healthcare "Clinical Hospital #8 of Yaroslavl"
Yaroslavl, 150030
Sverdlovsky Regional Clinical Hospital of Wars Veterans
Yekaterinburg, 620905
United States20 sites
Alexandria Cardiology Clinic
Alexandria, Louisiana, 71301
Endeavor Medical Research, PLC
Alpena, Michigan, 49707
Masters of Clinical Research, Inc.
Augusta, Georgia, 30909
Columbus Cardiology Associates
Columbus, Georgia, 31909
Cross Country Cardiology
Edgewater, New Jersey, 07020
Central Cardiology Associates
Elizabethtown, Kentucky, 42701
South Florida Research Solutions, LLC
Hollywood, Florida, 33021
Med-Tech Research
Houston, Texas, 77024
Humble Cardiology Associates
Humble, Texas, 77338
Kore CV Research
Jackson, Tennessee, 38305
Baptist Heart Specialist
Jacksonville, Florida, 32207
Wellmont Cardiovascular Associates Heart Institute
Johnson City, Tennessee, 37604
Cardiology and Medicine Clinic
Little Rock, Arkansas, 72204
Clinical Trials Management, LLC
Mandeville, Louisiana, 70471
Merced Heart Associates
Merced, California, 95340
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, 55407
Spectrum Clinical Research Institute, Inc
Moreno Valley, California, 92553
Research Integrity, LLC
Owensboro, Kentucky, 42303
Sacramento Heart and Vascular Research Center
Sacramento, California, 95825
Clinical Research of Central Florida
Winter Haven, Florida, 33880
Poland14 sites
Pomorskie Centra Kardiologiczne S.A.
Gdansk, 80126
NZOZ Sródmiescie Sp z o.o.
Gdynia, Pomeranian Voivodeship, 81-394
S.P. Specjalistyczny Szpital Zachodni im.JP II
Grodzisk Mazowiecki, 05-825
Specjalistyczna Praktyka Lekarska Leszek Bryniarski
Krakow, Lesser Poland Voivodeship, 30-082
NZOZ Revita Poradnia Kardiologiczna
Krakow, Lesser Poland Voivodeship, 31-949
Krakowski Szpital Specjalistyczny im.JPII
Krakow, 31-202
MULTI-MED PLUS Sp. z o.o.
Lódz, Łódź Voivodeship, 90-553
KO-MED Marek Konieczny
Puławy, Lublin Voivodeship, 24-100
Niepubliczny Zakład Opieki Zdrowotnej Przychodnia Zdrowia "Zadębie"
Skierniewice, Łódź Voivodeship, 96-100
Instytut Kardiologii
Warsaw, Masovian Voivodeship, 02-637
Instytut Kardiologii
Warsaw, Masovian Voivodeship, 04-628
Synexus SCM Sp. z o.o. Oddział w Warszawie
Warsaw, 01-192
Centrum Badawcze Współczenej Terapii
Warsaw, 02-679
Slaskie Centrum Chorób Serca w Zabrzu
Zabrze, 41-800
Ukraine10 sites
Donetsk National Medical University, Department of Internal Medicine #1 based on Department of Emergency Cardiology and Rehabilitation of Institute of Urgent and Recovery Surgery named after V. K. Gusak
Donetsk, 83045
Central Clinical Hospital of Ukrzaliznitsia, Cardiology department
Kharkiv, 61103
Kharkiv Medical Academy of Postgraduate Education, Department of cardiology and functional diagnostics based on City Clinical Hospital #8, Department of Cardiology #2
Kharkiv, 61176
Central polyclinic of Pechersk district, Department of cardiology
Kyiv, 01103
Kyiv City Clinical Hospital #1, Department of Emergency Cardiology
Kyiv, 02091
Kyiv city clinical hospital #5
Kyiv, 03115
Department of Diabetology of National Medical Academy of Postgraduate Education named after P.L.Shupyk based on Day Time Hospital of Administration of Medical Service and Rehabilitation of "ARTEM" SHC
Kyiv, 04050
SI "Institute of Gerontology of AMS of Ukraine"
Kyiv, 04114
Lviv National Medical University named after Danylo Halytsky, Department of Propaedeutics of Internal Medicine #1 based on Polyclinic Department of Municipal City Clinical Hospital #5
Lviv, 79044
SI Odessa Regional Cardiological Dispensary
Odesa, 65025
Canada8 sites
Dr. Roger Labonté Professional Medicine Corp.
Greater Sudbury, Ontario, P3E 3B8
High Desert Medical Group
Lancaster, 93534
Montréal General Hospital
Montreal, Quebec, H3G 1A4
Montreal Heart Institute
Montreal, H1T 1C8
SKDS Research Inc
Newmarket, Ontario, L3Y 5G8
London Road Diagnostic Clinic and Medical Centre
Ontario, N7T 4X3
Topsail Road Medical Clinic
St. John's, A1E 2E2
Aniol Gupta MD
Toronto, Ontario, M9V 4B4
Czechia7 sites
Vojenska Nemocnice Brno
Brno, 636 00
Cardiocentrum Kladno s.r.o.
Kladno, 27280
Poliklinika Modrany - Kardiologie
Prague, 14300
Fakultní Nemocnice v Motole
Prague, 150 06
Corintez s.r.o.
Prague, 158 00
Centrum klinického výzkumu, s.r.o.
Príbram, 26101
Nemocnice Slaný
Slaný, 27401
Georgia7 sites
Tbilisi State Medical University Alexandre Aladashvili University Clinic
Tbilisi, 0102
Amtel Hospital First Clinical LLC
Tbilisi, 0144
Clinic "Guli"
Tbilisi, 0144
Cardio-Reanimation Clinic LTD
Tbilisi, 0159
Emergency Cardiology Center by Academician G. Chapidze LTD
Tbilisi, 0159
Tbilisi Heart and Vascular Clinic LTD
Tbilisi, 0159
Multiprofile Clinical Hospital of Tbilisi #2 LTD
Tbilisi, 0164
Germany7 sites
Charité Campus Virchow Klinikum
Berlin, 13353
Städtische Kliniken Bielefeld
Bielefeld, 33604
Sankt Johannes-Hospital Dortmund
Dortmund, 44137
Universitätsklinikum Göttingen
Göttingen, 37099
Gemeinschaftspraxis fur Kardiologie
Heidelberg, 69115
Praxis Fur Innere Medizin Kardiologie, Pneumologic und Allergologie
Mannheim, 68165
Universitätsmedizin Mannheim
Mannheim, 68169
Bulgaria6 sites
Diagnostic Consultative Center, Ascendent Cardiological Out-Patient Office
Sofia, 1202
MHAT "Tsar Boris III"
Sofia, 1233
National Cardiology Center, Cardiology Clinic - III
Sofia, 1309
MHAT "Vita", Cardiology Department
Sofia, 1505
UMHAT "Tsaritsa Yoanna" - ISUL, Cardiology Clinic
Sofia, 1527
Military Medical Academy, Clinic of Cardiology and Intesive Care
Sofia, 1606
Israel6 sites
Barzilai Medical Center, Cardiology Dept.
Ashkelon, 78287
Assaf Harofeh Medical Centre
Be’er Ya‘aqov, 70300
Shaare Zedek Medical Center
Jerusalem, 91004
Kaplan Medical Center
Rehovot, 76100
Ziv Medical Center
Safed, 13100
Tel Aviv Souraski Medical Center
Tel Aviv, 64239
Slovakia6 sites
ALIAN, s.r.o.
Bardejov, 085 01
Cardioconsult, s.r.o.
Bratislava, 811 04
Kardiovaskulárne centrum, s.r.o.
Bratislava, 831 01
CARDIO D&R, s.r.o.
Košice, 040 22
KARDIOMED, s.r.o.
Lučenec, 984 01
Kardiocentrum Nitra, s.r.o.
Nitra, 949 01
Slovenia3 sites
University Clinic of Respiratory and Allergic Diseases Golnik
Golnik, 4204
University Klinicni Center Ljubljana
Ljubljana, 1000
General Hospital Murska Sobota
Murska Sobota, 9001
Belarus2 sites
State Institution "Gomel regional clinical hospital"
Homyel, 246029
State Inst Rep Scientific and Practical center
Minsk, 220036
Serbia2 sites
Cardiology Clinic, Clinical Center Serbia
Belgrade, 11000
Institute of Cardiovascular Diseases
Kamenitz, 21204
About this study
Official title: A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Parallel Study of Ranolazine in Subjects With Chronic Stable Angina and Coronary Artery Disease With a History of Type 2 Diabetes Mellitus
This study will evaluate the effect of ranolazine compared to placebo on the average weekly angina frequency in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM), and whether ranolazine can reduce the frequency of angina (chest pain) attacks, compared to a placebo. Subjects will be asked to record their daily angina episodes in a diary at the end of each study day. Ranolazine is approved for the treatment of chronic angina, and is not approved for the treatment of T2DM.
Read the detailed description
Participants who meet the eligibility criteria at screening will enter a 4-to 6-week Qualifying Period. The allowed concomitant antianginal medication(s) must be maintained at a stable dose throughout the study. Participants will document the number of angina episodes, number of sublingual nitroglycerin doses taken, and a dyspnea score (on a scale from 1 to 5) on a daily basis in a diary. Participants eligible to stay in the study after the Qualifying Period will enter the 8-week double-blind dosing phase. Participants will have study visits at the end of Weeks 2 and 8. Participants will continue to document the number of angina episodes and number of sublingual nitroglycerin doses taken as well as a dyspnea score on a daily basis by the end of each day in their diary. In addition, participants will be called during Week 2 and at the end of Week 5 to encourage compliance. A safety follow-up phone call will be made 14 days after the last study visit or early discontinuation.
- Being tested
- Ranolazine, Ranolazine placebo
- Keywords
- Chronic angina, Angina pectoris, Coronary artery disease, Type 2 Diabetes Mellitus
- Medical subject headings
- Angina Pectoris, Coronary Artery Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called Ranexa®
Ranolazine placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Qualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period.
Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks. Receives: Drug: Ranolazine placebo |
| Ranolazine | Experimental | Qualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period.
Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks. Receives: Drug: Ranolazine; Drug: Ranolazine placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment
Average weekly angina frequency was defined as the total number of angina episodes reported during the last 6 weeks of treatment divided by 6 weeks.
For subjects who terminated with less than 6 weeks of treatment, frequency was calculated as the total number of angina episodes reported during the treatment period divided by the subject's actual duration of treatment.
Measured: 6 weeks
Secondary outcomes (5)
Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment
Average weekly frequency of sublingual nitroglycerin use was defined as the total number reported during the last 6 weeks of treatment divided by the duration corresponding to the last 6 weeks of treatment.
Measured: 6 weeks
Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency
For each participant, the percentage of the last 6 weeks on treatment during which the angina frequency was less than or equal to 50% of the baseline average weekly angina frequency was determined.
Measured: 6 weeks
Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was ≤ 50% of the Baseline Average Weekly Angina Frequency
Measured: 6 weeks
Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores
The range of each health domain score is 0-100, with 0 indicating a poorer health state and 100 indicating a better health state. An increase in score indicates an improvement in health state. Participants were asked to complete the survey at randomization (prior to receiving treatment), and at end of treatment visit (Week 8) or early study drug discontinuation or early termination visit. The survey asked participants for responses specific to the preceding 4 weeks prior to completing the survey.
Measured: Up to 8 weeks
Patient's Global Impression of Change (PGIC) Scale Score
The PGIC was completed at the end of treatment/last visit.The PGIC scale measures the change in the participant's overall status since the beginning of the study on a scale ranging from 1 (no change or worse) to 7 (very much improved).
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2011 (estimated)
- Study startSep 2011
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Angina PectorisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 949 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patrick Yue, MD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01425359
- Sponsor's protocol ID
- GS-US-259-0133
- Acronym
- TERISA
- Status last verified
- Oct 2014
- First submitted
- 24 Aug 2011
- Last updated
- 4 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Arnold SV, Kosiborod M, Li Y, Jones PG, Yue P, Belardinelli L, Spertus JA. Comparison of the Seattle Angina Questionnaire With Daily Angina Diary in the TERISA Clinical Trial. Circ Cardiovasc Qual Outcomes. 2014 Nov;7(6):844-50. doi: 10.1161/CIRCOUTCOMES.113.000752. Epub 2014 Sep 23.
PubMed 25249560Roubinian NH, Escobar GJ, Liu V, Gardner MN, Carson JL, Kleinman SH, Murphy EL; NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-III). Decreased red blood cell use and mortality in hospitalized patients. JAMA Intern Med. 2014 Aug;174(8):1405-7. doi: 10.1001/jamainternmed.2014.2889. No abstract available.
PubMed 24978650Kosiborod M, Arnold SV, Spertus JA, McGuire DK, Li Y, Yue P, Ben-Yehuda O, Katz A, Jones PG, Olmsted A, Belardinelli L, Chaitman BR. Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina). J Am Coll Cardiol. 2013 May 21;61(20):2038-45. doi: 10.1016/j.jacc.2013.02.011. Epub 2013 Mar 10.
PubMed 23500237
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Parallel Study of Ranolazine in Subjects With Chronic Stable Angina and Coronary Artery Disease With a History of Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01425359
- Acronym / sponsor ID
- TERISA / GS-US-259-0133
- Keywords
- Chronic angina, Angina pectoris, Coronary artery disease, Type 2 Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 949 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 30 Aug 2011 (estimated)
- Results
- Posted 4 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effect of ranolazine compared to placebo on the average weekly angina frequency in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM), and whether ranolazine can reduce the frequency of angina (chest pain) attacks, compared to a placebo. Subjects will be asked to record their daily angina episodes in a diary at the end of each study day. Ranolazine is approved for the treatment of chronic angina, and is not approved for the treatment of T2DM.
Detailed description
Participants who meet the eligibility criteria at screening will enter a 4-to 6-week Qualifying Period. The allowed concomitant antianginal medication(s) must be maintained at a stable dose throughout the study. Participants will document the number of angina episodes, number of sublingual nitroglycerin doses taken, and a dyspnea score (on a scale from 1 to 5) on a daily basis in a diary. Participants eligible to stay in the study after the Qualifying Period will enter the 8-week double-blind dosing phase. Participants will have study visits at the end of Weeks 2 and 8. Participants will continue to document the number of angina episodes and number of sublingual nitroglycerin doses taken as well as a dyspnea score on a daily basis by the end of each day in their diary. In addition, participants will be called during Week 2 and at the end of Week 5 to encourage compliance. A safety follow-up phone call will be made 14 days after the last study visit or early discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Ranolazine placeboQualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks. |
| Ranolazine | Experimental | Drug: Ranolazine, Drug: Ranolazine placeboQualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent
- Males and females aged at least 18 years
- At least a 3-month history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin
- CAD documented by one or more of the following:
- Treatment with up to 2 antianginal therapies at a stable dose for at least 2 weeks prior to the Qualifying Period.
Key exclusion criteria (19 listed)
- New York Heart Association (NYHA) Class III and IV
- Acute coronary syndrome in the prior 2 months or planned coronary revascularization during the study period
- Stroke or transient ischemic attack within 6 months prior to Screening
- QTc > 500 milliseconds
- Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanolazineAlso: Ranexa® | Drug | Ranolazine |
| Ranolazine placebo | Drug | Placebo, Ranolazine |
Primary outcome
Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment
Time frame: 6 weeks
Average weekly angina frequency was defined as the total number of angina episodes reported during the last 6 weeks of treatment divided by 6 weeks. For subjects who terminated with less than 6 weeks of treatment, frequency was calculated as the total number of angina episodes reported during the treatment period divided by the subject's actual duration of treatment.
5 secondary outcomes
Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment
Time frame: 6 weeks
Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency
Time frame: 6 weeks
Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was ≤ 50% of the Baseline Average Weekly Angina Frequency
Time frame: 6 weeks
Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores
Time frame: Up to 8 weeks
Patient's Global Impression of Change (PGIC) Scale Score
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25249560Arnold SV, Kosiborod M, Li Y, Jones PG, Yue P, Belardinelli L, Spertus JA. Comparison of the Seattle Angina Questionnaire With Daily Angina Diary in the TERISA Clinical Trial. Circ Cardiovasc Qual Outcomes. 2014 Nov;7(6):844-50. doi: 10.1161/CIRCOUTCOMES.113.000752. Epub 2014 Sep 23.
- Derived from this study: PubMed 24978650Roubinian NH, Escobar GJ, Liu V, Gardner MN, Carson JL, Kleinman SH, Murphy EL; NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-III). Decreased red blood cell use and mortality in hospitalized patients. JAMA Intern Med. 2014 Aug;174(8):1405-7. doi: 10.1001/jamainternmed.2014.2889. No abstract available.
- Derived from this study: PubMed 23500237Kosiborod M, Arnold SV, Spertus JA, McGuire DK, Li Y, Yue P, Ben-Yehuda O, Katz A, Jones PG, Olmsted A, Belardinelli L, Chaitman BR. Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina). J Am Coll Cardiol. 2013 May 21;61(20):2038-45. doi: 10.1016/j.jacc.2013.02.011. Epub 2013 Mar 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Yue, MD study director
Gilead Sciences
135 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ranolazine in people with Angina Pectoris and Coronary Artery Disease, run by Gilead Sciences at 135 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 135 sites in Russia, United States, Poland, Ukraine, Canada and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01425359, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2014.