AnginaPhase 3NCT01174173
Ranolazine and Pulmonary Hypertension
A Phase 3 study testing Ranolazine in people with Angina and Pulmonary Arterial Hypertension, run by Northwestern University at 1 site in United States.
Trial summary
The purpose of the study is to determine if the medication, ranolazine (study drug), can help improve blood flow to your heart, increase your exercise capacity and improve your quality of life (QOL). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Angina, Pulmonary Arterial Hypertension
- What is being tested?
- Ranolazine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Oct 2014
- Phase
- Phase 3
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- World Health Organization (WHO) Group 1 PAH, defined as a pulmonary hypertension with mean pulmonary artery pressure > 25 mmHg, pulmonary capillary wedge pressure < 15 mmHg, and pulmonary vascular resistance > 3 Wood units.
- Right ventricular dysfunction, defined as RV fractional area change < 32% or RV tricuspid annular plane systolic excursion (TAPSE) < 15 mm.
- Symptoms of angina or angina equivalent (exertional dyspnea, exertional epigastric pain, exertional nausea).
- New York Heart Association functional class II or III symptoms.
- Stable doses of pulmonary vasodilators (prostacyclins, endothelin receptor antagonists, phosphodiesterase inhibitors), with no new therapy initiation or dose escalation > 50% in the 4 weeks prior to randomization.
- Age 18-80 years.
Who cannot join
- Acute coronary syndrome or coronary revascularization within the prior 3 months.
- Patients with unstable angina.
- Patients with Class IV congestive heart failure.
- Planned revascularization, pacemaker or defibrillator placement during the study period.
- Changes in antianginal medical therapy likely to occur during the study period.
- Corrected QT interval measurement >500 ms.
Show all 20Show fewer
- Patients with pre-existing QT prolongation (including congenital long QT syndrome) or receiving other QT prolonging drugs (including Class Ia-e.g., quinidine, Class III-e.g., dofetilide, sotalol, antiarrhythmics; antipsychotics (e.g., thioridazine, ziprasidone), or known history of complex ventricular arrhythmias requiring antiarrhythmic medications or ICD implantation.
- Patients with known history of hepatic dysfunction.
- Current use of strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir and diltizaem.
- Patients with pacemakers, cochlear implants, aneurysm clips, who have worked with metal.
- Patients with metallic hardware, implants, or prostheses will consult with the radiologist/cardiologist prior to the study.
- Patients with severe or end stage renal disease (an estimated GFR < 30 mL/min/1.73 m).
- Women who are pregnant or lactating
- Any contraindications for the use of a right heart catheter including, but not limited to:
- Pulmonic or tricuspid valve stenosis
- Prosthetic pulmonic or tricuspid valve
- Right atrial or ventricular masses
- Previous pneumonectomy
- Risk of severe arrhythmias, including left bundle branch block (LBBB)
- Subjects unable to perform cardiopulmonary exercise testing will be excluded (i.e. extensive musculoskeletal disease)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Ranolazine in Patients With Angina Due to Right Ventricular Ischemia in Pulmonary Arterial Hypertension
The purpose of the study is to determine if the medication, ranolazine (study drug), can help improve blood flow to your heart, increase your exercise capacity and improve your quality of life (QOL). For this study, you will be asked to perform several tests in order to determine if your heart function, exercise capacity, chest pain and QOL have improved after 3 months of treatment with ranolazine. Ranolazine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of angina.
Read the detailed description
This study is looking to enroll patients with pulmonary hypertension (PH). PH is abnormally high blood pressure in the arteries of the lungs. It makes the right side of the heart need to work harder than normal and is usually caused by a narrowing of the small arteries of the lung. This narrowing makes it harder for the right side of the heart to circulate the blood to the lungs. Over time, the right side of the heart may become enlarged and symptoms (such as angina [chest pain] shortness of breath, fatigue, edema) begin to appear.
Ranolazine is a safe, well-tolerated, and FDA-approved medication for the treatment of chronic stable angina. Ranolazine may potentially improve blood flow to the right ventricle (RV), thereby relieving angina while simultaneously improving RV performance and contractility. This latter effect may increase stroke volume and cardiac output which could translate into benefits in exercise capacity and improved quality of life.
The purpose of this single center, non-randomized, prospective pilot study is to investigate the effects of 3 months treatment with ranolazine on pulmonary artery hemodynamics, exercise capacity and quality of life in patients with PAH and symptoms of angina or angina equivalent.
- Conditions
- Angina, Pulmonary Arterial Hypertension
- Being tested
- Ranolazine
- Keywords
- Angina, Right Ventricular Ischemia, Pulmonary Arterial Hypertension, Pulmonary Hypertension
- Medical subject headings
- Angina Pectoris, Pulmonary Arterial Hypertension, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called Ranexa
ranolazine 1000 mg PO BID for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Ranolazine | Experimental | 1000 mg PO BID Receives: Drug: Ranolazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improve Angina Symptoms
Assessed as average improvement in WHO Functional Class. The WHO Functional Class score ranges from 1 to 4, with higher scores indicating more impairment
Measured: 3 months
6-Minute Walk Test
Improve Exercise Capacity measured by 6-Minute Walk Test
Measured: 3 Months
Improve Quality of Life
The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The scores are averaged and transformed to a range of 0-100, in which higher scores reflect better health status and was performed at the conclusion of the study.
Measured: 3 Months
Secondary outcomes (3)
RV Perfusion on Cardiac MRI
The majority of patients did not undergo cardiac MRI because it was difficult for the patients to tolerate the imaging study. Therefore, we were not able to assess change in RV perfusion.
Measured: 3 months
Absolute RV Longitudinal Strain
Change in absolute right ventricular (RV) longitudinal strain as assessed by exercise stress echocardiography with speckle-tracking echocardiography at baseline and conclusion of the study. An increase in exercise-induced change in RV longitudinal strain between baseline to conclusion of the study is indicative of improved RV function. If absolute RV longitudinal strain increases with exercise, that is a sign that the RV is working well. If absolute RV longitudinal strain decreases with exercise, that is a sign that the RV is not working well. Therefore, between baseline and conclusion of the study, if exercise-induced change in RV strain increases that means that the RV is working better at the conclusion of the study.
Measured: 3 months
Right Ventricular Hemodynamics
Mean pulmonary artery pressure was assessed invasively by right heart catheterization at the conclusion of the study to estimate right ventricular hemodynamics.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2010 (estimated)
- Study startJun 2010
- Primary completionJan 2014
- Study completionOct 2014
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 (1)Papers the sponsor has linked to this study.
- Other trials for AnginaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Principal investigator, Sanjiv Shah, Northwestern University
- Investigators
- Sanjiv Shah, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01174173
- Sponsor's protocol ID
- STU00030314
- Status last verified
- Apr 2018
- First submitted
- 23 Jul 2010
- Last updated
- 11 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Khan SS, Cuttica MJ, Beussink-Nelson L, Kozyleva A, Sanchez C, Mkrdichian H, Selvaraj S, Dematte JE, Lee DC, Shah SJ. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study. Pulm Circ. 2015 Sep;5(3):547-56. doi: 10.1086/682427.
PubMed 26401256
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ranolazine in Patients With Angina Due to Right Ventricular Ischemia in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01174173
- Acronym / sponsor ID
- STU00030314
- Conditions
- Angina, Pulmonary Arterial Hypertension
- Keywords
- Angina, Right Ventricular Ischemia, Pulmonary Arterial Hypertension, Pulmonary Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Jun 2010
- Primary completion
- Jan 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 3 Aug 2010 (estimated)
- Results
- Posted 23 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine if the medication, ranolazine (study drug), can help improve blood flow to your heart, increase your exercise capacity and improve your quality of life (QOL). For this study, you will be asked to perform several tests in order to determine if your heart function, exercise capacity, chest pain and QOL have improved after 3 months of treatment with ranolazine. Ranolazine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of angina.
Detailed description
This study is looking to enroll patients with pulmonary hypertension (PH). PH is abnormally high blood pressure in the arteries of the lungs. It makes the right side of the heart need to work harder than normal and is usually caused by a narrowing of the small arteries of the lung. This narrowing makes it harder for the right side of the heart to circulate the blood to the lungs. Over time, the right side of the heart may become enlarged and symptoms (such as angina [chest pain] shortness of breath, fatigue, edema) begin to appear.
Ranolazine is a safe, well-tolerated, and FDA-approved medication for the treatment of chronic stable angina. Ranolazine may potentially improve blood flow to the right ventricle (RV), thereby relieving angina while simultaneously improving RV performance and contractility. This latter effect may increase stroke volume and cardiac output which could translate into benefits in exercise capacity and improved quality of life.
The purpose of this single center, non-randomized, prospective pilot study is to investigate the effects of 3 months treatment with ranolazine on pulmonary artery hemodynamics, exercise capacity and quality of life in patients with PAH and symptoms of angina or angina equivalent.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ranolazine | Experimental | Drug: Ranolazine1000 mg PO BID |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- World Health Organization (WHO) Group 1 PAH, defined as a pulmonary hypertension with mean pulmonary artery pressure > 25 mmHg, pulmonary capillary wedge pressure < 15 mmHg, and pulmonary vascular resistance > 3 Wood units.
- Right ventricular dysfunction, defined as RV fractional area change < 32% or RV tricuspid annular plane systolic excursion (TAPSE) < 15 mm.
- Symptoms of angina or angina equivalent (exertional dyspnea, exertional epigastric pain, exertional nausea).
- New York Heart Association functional class II or III symptoms.
- Stable doses of pulmonary vasodilators (prostacyclins, endothelin receptor antagonists, phosphodiesterase inhibitors), with no new therapy initiation or dose escalation > 50% in the 4 weeks prior to randomization.
Key exclusion criteria (20 listed)
- Acute coronary syndrome or coronary revascularization within the prior 3 months.
- Patients with unstable angina.
- Patients with Class IV congestive heart failure.
- Planned revascularization, pacemaker or defibrillator placement during the study period.
- Changes in antianginal medical therapy likely to occur during the study period.
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: Ranexaranolazine 1000 mg PO BID for 3 months | Drug | Ranolazine |
Primary outcome
Improve Angina Symptoms
Time frame: 3 months
Assessed as average improvement in WHO Functional Class. The WHO Functional Class score ranges from 1 to 4, with higher scores indicating more impairment
6-Minute Walk Test
Time frame: 3 Months
Improve Exercise Capacity measured by 6-Minute Walk Test
Improve Quality of Life
Time frame: 3 Months
The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The scores are averaged and transformed to a range of 0-100, in which higher scores reflect better health status and was performed at the conclusion of the study.
3 secondary outcomes
RV Perfusion on Cardiac MRI
Time frame: 3 months
Absolute RV Longitudinal Strain
Time frame: 3 months
Right Ventricular Hemodynamics
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26401256Khan SS, Cuttica MJ, Beussink-Nelson L, Kozyleva A, Sanchez C, Mkrdichian H, Selvaraj S, Dematte JE, Lee DC, Shah SJ. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study. Pulm Circ. 2015 Sep;5(3):547-56. doi: 10.1086/682427.
- Bluhm Cardiovascular Institute Clinical Trials Unit research studiesLink provided by the sponsor.
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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.
Sanjiv Shah, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ranolazine in people with Angina and Pulmonary Arterial Hypertension, run by Northwestern University at 1 site in United States.
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 6 inclusion and 20 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 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 23 Apr 2015). 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?
Improve Angina Symptoms (time frame: 3 months). The study lists 3 primary outcomes in all. 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 NCT01174173, which also lists 1 linked publication.
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 11 May 2018.