Pulmonary HypertensionPhase 4NCT02133352
Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction
A Phase 4 study testing Ranolazine in people with Pulmonary Hypertension and Diastolic Left Ventricular Dysfunction, run by Boston University at 1 site in United States.
Trial summary
This is a single center, open-label trial designed to assess the safety and efficacy of ranolazine (Ranexa) in patients with pulmonary hypertension associated with left ventricular diastolic dysfunction. All patients will receive active drug. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Hypertension, Diastolic Left Ventricular Dysfunction
- What is being tested?
- Ranolazine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to May 2014
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written consent prior to any study procedure
- Men or women, ages 18 to 75 years
- Suspicion of Pulmonary Hypertension by echo (RVSP ≥ 50mmHg) or diagnosis of Pulmonary Hypertension by cardiac cath (mPAP ≥25 mmHg at rest)
- LVEF ≥50%, (by ECHO, radionuclide imaging, or cardiac cath)
- 6MWT distance ≥150m and ≤450m at both time points within the Screening Period
- NYHA/WHO functional class II-III
- RHC measurements on Study Day 1: 1) mean pulmonary artery pressure (MPAP) ≥25 mmHg; 2) pulmonary artery occlusion pressure (PAOP) ≥18 mmHg and ≤30 mmHg; 3) pulmonary artery diastolic pressure (PADP) - PAOP ≤10 mmHg
Who cannot join
- Presence or history of any of the following cardiovascular co-morbidities or conditions: Hypotension at Screening (defined as a resting SBP≤90mmHg). Hypertension at Screening (defined as resting SBP ≥200mmHg), Unstable cardiovascular disease including paroxysmal atrial fibrillation or unstable angina, Amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis, History of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention, Significant valvular heart disease, Cerebrovascular accident or transient ischemic attack
- Exercise tolerance limited by non-cardiac causes (exercise-induced asthma, malignancy, obesity, musculoskeletal disorder).
- Clinically significant psychiatric, addictive (DSM-IV criteria), neurologic disease or condition that would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the protocol
- Any other condition or co-morbidity that, in the opinion of the Investigator, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the protocol
- Clinically significant laboratory abnormalities, including: Positive Hep B surface antigen or Hep C antibody, Positive HIV test within one year of Study Day 1, Serum alanine aminotransferase (ALT) ≥ 2.0 x ULN, Total bilirubin ≥ 1.2 x ULN (unless evidence of Gilbert's syndrome). Serum creatinine ≥ 2.5mg/dL (or calculated creatinine clearance less than or equal to 30mL/min). Hemoglobin less than or equal to 10g/dL (subject may qualify for the study following diagnosis and treatment of anemia, if the anemia is due to iron and/or vitamin deficiency).
- Patients with moderate or severe hepatic impairment (Child-Pugh Classes B or C) or requiring hemidialysis.
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- Subject has received any other investigational medication within the 30 days prior to Screening
- Prior treatment with ranolazine
- Pregnancy or lactation
- Women of childbearing potential and men without vasectomies who are not using barrier method of contraception
- Subject has the presence, or history, of malignancy that required significant medical intervention within the preceding 3 months and/or is likely to result in death within the next 2 years (exception of basal cell, non-metastatic squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix)
- Treatment for pulmonary hypertension with epoprostenol (Flolan), treprostinil (Remodulin), iloprost (Ventavis), bosentan (Tracleer), ambrisentan (Letairis), sildenafil (Revatio), tadalafil (Adcirca). The use of sildenafil, tadalafil, or vardenafil is prohibited for any reason within 7 days of hemodynamic assessments on Days 1 and 180).
- Patients with QTc > 500 msec at baseline
- Treatment with potent CYP3A inhibitors, including ketoconazole, itraconazonle, clarithromycin, nefazodone, nelfinavir, indinavir, \& saquinavir
- Treatment with CYP3A inducers, including rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's wort.
Trial locations and contacts
1 site in 1 country.
United States1 site
Boston University Medical Center
Boston, Massachusetts, 02118
About this study
Official title: Proof of Concept Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction
This is a single center, open-label trial designed to assess the safety and efficacy of ranolazine (Ranexa) in patients with pulmonary hypertension associated with left ventricular diastolic dysfunction. All patients will receive active drug. The study includes a screening period, 6 month treatment period and a follow up period. Eligible patients who provide informed consent and who meet all inclusion/exclusion criteria will be enrolled in this study.
There is neither proven therapy for patients with diastolic dysfunction-associated pulmonary hypertension nor for patients with diastolic dysfunction alone. Ranolazine, an inhibitor of cardiac repolarization (sodium channels), could represent a new and effective treatment of this entity.
Read the detailed description
This single center, prospective, open-label trial to assess the safety and efficacy of ranolazine in subjects with pulmonary hypertension associated with left ventricular diastolic dysfunction includes a screening period, 6 month treatment period and a follow up period. Eligible subjects who provide informed consent and who meet all inclusion/exclusion criteria will be enrolled in this study. All subjects will receive active study drug. There is no placebo group or use of control subjects. Treating will begin with 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine will be limited to 500 mg BID in patients taking moderate inhibitors of CYP3A, including diltiazem, verapamil, aprepitant, erythromycin, fluconazole, grapefruit juice or grapefruit-containing products. During the Treatment Period subjects will be provided bottles of study medication to take home. Throughout the Treatment Period, subjects will return to the clinic for safety and/or efficacy assessments as well as resupply of Study Medication. Once the Treatment Period is complete, subjects will return to the clinic for a Follow-Up visit 14 days after the last dose of study medication, for a final safety assessment. Other therapies or possibly extension of the ranolazine treatment may be considered after completion of the Treatment Period at the discretion of the Investigator and will be recorded at the follow-up visit. Subjects who continue taking ranolazine (as part of there clinical care), will be asked to return for a 1 year follow up visit for safety and efficacy assessments.
As part of Amendment 2 (submitted November 2013), subjects who continue on ranolazine after the 6 month treatment period (as part of their clinical care) will be asked to return for further follow-up testing to better assess the safety and efficacy of the drug. The visit can be conducted once the patient has been on drug for a total of one year or greater (including the 6 month treatment period). This would replace the 1 Year follow-up visit for subjects who have not yet completed the visit and will be an additional visit for those subjects who have.
Subjects can opt to continue on ranolazine regardless of if they agree to complete the Post Treatment Follow up visit. They do not have to continue with the study after the treatment phase has been completed in order to stay on ranolazine. The PI and study personnel will complete the required forms for the Ranexa Connect application if patient wishes to stay on drug. The Ranexa Connect Program assists patients in obtaining insurance coverage of ranolazine and financial assistance if needed.
This is a 6 month, single center, prospective, open-label trial. All subjects will be receiving active treatment, ranolazine at doses approved by the FDA. Subjects will begin treatment at 500mg twice daily and increase to 1000mg twice daily as tolerated after 2 weeks. Subjects will take study drug twice daily with or without food. Ranolazine will be limited in subjects taking CYP3A including diltiazem, verapamil, arprepitant, erythromycin, fluconazole, grapefruit juice or grapefruit juice containing products. The study will consist of 3 periods: a screening period, a treatment period, and a follow-up period.
Subjects will be asked to come to the study center for 9-10 visits over the course of 6 months. Other therapies or possibly extension of the ranolazine treatment may be considered after completion of the treatment period at the discretion of the Investigator at the follow up visit. Subjects who continue on ranolazine after completion of the treatment period of the study will be asked to return for follow up testing.
- Being tested
- Ranolazine
- Keywords
- pulmonary hypertension, diastolic dyfunction
- Medical subject headings
- Hypertension, Pulmonary, Ventricular Dysfunction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called Ranexa
Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
| Study group | Role | What they receive |
|---|---|---|
| Ranolazine | Experimental | Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Receives: Drug: Ranolazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR)
Assess the percent change in mPAP, PAOP and pulmonary vascular resistance (PVR) by RHC.
Additional RHC completed at optional follow up for patients remaining on ranolazine upon completion of 180 day period.
Measured: 180 days
Secondary outcomes (5)
Percent Change in Other Hemodynamic Parameters
Assess % change in other hemodynamic parameters, by RHC, from baseline afeter 180 days of ranolazine.
Right atrial pressure (RAP) Systolic pulmonary artery pressure (SPAP) Diastolic pulmonary artery pressure (DPAP) Cardiac output (CO) Cardiac index (CI)
Measured: 180 days
6 Minute Walk Test (6MWT)
Assess the change from baseline in 6 minute walk test (6MWT) after 180 days of twice daily ranolazine Optional follow up for some patients also includes 6MWT.
Measured: 180 days
Change in Cardiac Size and Function
Assess changes from baseline in measurements of cardiac size and function obtained by MRI after 180 days of twice daily ranolazine.
An additional MRI may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.
Measured: 180 days
Change in Echocardiogram Parameters (LVEF)
To assess the changes from baseline in echocardiographic parameters (left ventricular geometry and function, LVEF, evidence of diastolic dysfunction, SPAP, right ventricular geometry and function, degree of tricuspid regurgitation) after 180 days of twice daily ranolazine.
An additional echo may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.
Measured: 180 days
Change in BNP Cardiac Biomarker
Assess the change from baseline in BNP cardiac biomarkers after 180 days of twice daily ranolazine.
Cardiac biomarkers may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2014 (estimated)
- Study startJul 2011
- Primary completionMay 2013
- Study completionMay 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.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Boston 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Harrison Farber, MD, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02133352
- Sponsor's protocol ID
- 30217
- Status last verified
- May 2017
- First submitted
- 6 May 2014
- Last updated
- 17 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction
- ClinicalTrials.gov ID
- NCT02133352
- Acronym / sponsor ID
- 30217
- Keywords
- pulmonary hypertension, diastolic dyfunction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Boston UniversityUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Jul 2011
- Primary completion
- May 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 8 May 2014 (estimated)
- Results
- Posted 17 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single center, open-label trial designed to assess the safety and efficacy of ranolazine (Ranexa) in patients with pulmonary hypertension associated with left ventricular diastolic dysfunction. All patients will receive active drug. The study includes a screening period, 6 month treatment period and a follow up period. Eligible patients who provide informed consent and who meet all inclusion/exclusion criteria will be enrolled in this study.
There is neither proven therapy for patients with diastolic dysfunction-associated pulmonary hypertension nor for patients with diastolic dysfunction alone. Ranolazine, an inhibitor of cardiac repolarization (sodium channels), could represent a new and effective treatment of this entity.
Detailed description
This single center, prospective, open-label trial to assess the safety and efficacy of ranolazine in subjects with pulmonary hypertension associated with left ventricular diastolic dysfunction includes a screening period, 6 month treatment period and a follow up period. Eligible subjects who provide informed consent and who meet all inclusion/exclusion criteria will be enrolled in this study. All subjects will receive active study drug. There is no placebo group or use of control subjects. Treating will begin with 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine will be limited to 500 mg BID in patients taking moderate inhibitors of CYP3A, including diltiazem, verapamil, aprepitant, erythromycin, fluconazole, grapefruit juice or grapefruit-containing products. During the Treatment Period subjects will be provided bottles of study medication to take home. Throughout the Treatment Period, subjects will return to the clinic for safety and/or efficacy assessments as well as resupply of Study Medication. Once the Treatment Period is complete, subjects will return to the clinic for a Follow-Up visit 14 days after the last dose of study medication, for a final safety assessment. Other therapies or possibly extension of the ranolazine treatment may be considered after completion of the Treatment Period at the discretion of the Investigator and will be recorded at the follow-up visit. Subjects who continue taking ranolazine (as part of there clinical care), will be asked to return for a 1 year follow up visit for safety and efficacy assessments.
As part of Amendment 2 (submitted November 2013), subjects who continue on ranolazine after the 6 month treatment period (as part of their clinical care) will be asked to return for further follow-up testing to better assess the safety and efficacy of the drug. The visit can be conducted once the patient has been on drug for a total of one year or greater (including the 6 month treatment period). This would replace the 1 Year follow-up visit for subjects who have not yet completed the visit and will be an additional visit for those subjects who have.
Subjects can opt to continue on ranolazine regardless of if they agree to complete the Post Treatment Follow up visit. They do not have to continue with the study after the treatment phase has been completed in order to stay on ranolazine. The PI and study personnel will complete the required forms for the Ranexa Connect application if patient wishes to stay on drug. The Ranexa Connect Program assists patients in obtaining insurance coverage of ranolazine and financial assistance if needed.
This is a 6 month, single center, prospective, open-label trial. All subjects will be receiving active treatment, ranolazine at doses approved by the FDA. Subjects will begin treatment at 500mg twice daily and increase to 1000mg twice daily as tolerated after 2 weeks. Subjects will take study drug twice daily with or without food. Ranolazine will be limited in subjects taking CYP3A including diltiazem, verapamil, arprepitant, erythromycin, fluconazole, grapefruit juice or grapefruit juice containing products. The study will consist of 3 periods: a screening period, a treatment period, and a follow-up period.
Subjects will be asked to come to the study center for 9-10 visits over the course of 6 months. Other therapies or possibly extension of the ranolazine treatment may be considered after completion of the treatment period at the discretion of the Investigator at the follow up visit. Subjects who continue on ranolazine after completion of the treatment period of the study will be asked to return for follow up testing.
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: RanolazineRanolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Written consent prior to any study procedure
- Men or women, ages 18 to 75 years
- Suspicion of Pulmonary Hypertension by echo (RVSP ≥ 50mmHg) or diagnosis of Pulmonary Hypertension by cardiac cath (mPAP ≥25 mmHg at rest)
- LVEF ≥50%, (by ECHO, radionuclide imaging, or cardiac cath)
- 6MWT distance ≥150m and ≤450m at both time points within the Screening Period
Key exclusion criteria (15 listed)
- Presence or history of any of the following cardiovascular co-morbidities or conditions: Hypotension at Screening (defined as a resting SBP≤90mmHg). Hypertension at Screening (defined as resting SBP ≥200mmHg), Unstable cardiovascular disease including paroxysmal atrial fibrillation or unstable angina, Amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis, History of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention, Significant valvular heart disease, Cerebrovascular accident or transient ischemic attack
- Exercise tolerance limited by non-cardiac causes (exercise-induced asthma, malignancy, obesity, musculoskeletal disorder).
- Clinically significant psychiatric, addictive (DSM-IV criteria), neurologic disease or condition that would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the protocol
- Any other condition or co-morbidity that, in the opinion of the Investigator, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the protocol
- Clinically significant laboratory abnormalities, including: Positive Hep B surface antigen or Hep C antibody, Positive HIV test within one year of Study Day 1, Serum alanine aminotransferase (ALT) ≥ 2.0 x ULN, Total bilirubin ≥ 1.2 x ULN (unless evidence of Gilbert's syndrome). Serum creatinine ≥ 2.5mg/dL (or calculated creatinine clearance less than or equal to 30mL/min). Hemoglobin less than or equal to 10g/dL (subject may qualify for the study following diagnosis and treatment of anemia, if the anemia is due to iron and/or vitamin deficiency).
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: RanexaSingle arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated | Drug | Ranolazine |
Primary outcome
Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR)
Time frame: 180 days
Assess the percent change in mPAP, PAOP and pulmonary vascular resistance (PVR) by RHC. Additional RHC completed at optional follow up for patients remaining on ranolazine upon completion of 180 day period.
5 secondary outcomes
Percent Change in Other Hemodynamic Parameters
Time frame: 180 days
6 Minute Walk Test (6MWT)
Time frame: 180 days
Change in Cardiac Size and Function
Time frame: 180 days
Change in Echocardiogram Parameters (LVEF)
Time frame: 180 days
Change in BNP Cardiac Biomarker
Time frame: 180 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Harrison Farber, MD principal investigator
Boston University
1 site in 1 country: 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 Pulmonary Hypertension and Diastolic Left Ventricular Dysfunction, run by Boston 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 7 inclusion and 15 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 17 May 2017. 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 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 17 May 2017). 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?
Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR) (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 May 2017.