Pulmonary Arterial HypertensionPhase 1NCT01757808
A Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension
A Phase 1 study testing Ranolazine in people with Pulmonary Arterial Hypertension, run by University of Chicago at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety of ranolazine in people with pulmonary arterial hypertension (PAH) and who are receiving 1 or more background PAH therapies: ambrisentan, sildenafil,tadalafil, epoprostenol, treprostinil (IV, SC, inhaled), or iloprost. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Ranolazine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Jan 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All subjects age 18-72 yrs will have a diagnosis of PAH. PAH as defined as idiopathic PAH, heritable PAH or PAH associated with collagen vascular disease, congenital heart disease (repaired), or anorexigen use. A history of PAH as defined by hemodynamics at diagnosis by right heart catheterization defined as: mean PAP >25 mmHg with a normal PCWP < 15 mm Hg at rest and a PVR >3 Wood units.
- Baseline 6MW >150 meters
- Patients will be receiving FDA approved PAH monotherapy or dual therapy medications: including, ambrisentan (5,10mg), sildenafil (60-240mg), tadalafil (40mg), epoprostenol, treprostinil, or iloprost at stable doses for >90days.
- Receiving conventional therapy as clinically indicated (oxygen, calcium channel blockers, digoxin) with dose that is unchanged in the preceding 30 days prior to enrollment. This is excluding anticoagulants (warfarin) as the patient's dose may not be stable if the patient is having a cardiac catheterization at baseline within 30 days of enrollment and warfarin is being held.
Who cannot join
- PAH Category II-IV and Category I associated with all other etiologies: HIV, portopulmonary disease
- All subjects on monotherapy calcium blockers as "calcium blocker responders" irrespective of therapy
- All subjects receiving CY3P4 inducer (i.e. bosentan)
- Subjects with pulmonary hypertension due to significant interstitial lung disease, chronic obstructive pulmonary disease, congestive heart failure, valvular heart disease
- Subjects with (World Health Organization (WHO) functional Class I or Class IV
- Subjects with total lung capacity (TLC) < 60% of predicted
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- Subjects with significant obstructive lung disease with FEV1/FVC ratio < 70% of predicted
- Subjects with hypotension defined as systolic arterial pressure < 90 mmHg at baseline
- Subjects with hypertension defined as systolic arterial pressure >140 mmHg at baseline and a diastolic arterial pressure > 90 mmHg despite adequate medical therapy.
- Subjects with impaired renal function as defined as estimated glomerular filtration rate (eGFR) less than 45 mL/min/BSA (where BSA=1.73m2) as calculated by the Modification of Diet in Renal Disease (MDRD) equation:
- Patients with eGFR 45-50 mL/min/BSA may be enrolled only after discussion with data safety monitoring board. Patients with eGFR ≥ 50 mL/min/BSA may be enrolled without such a discussion.
- Subjects with liver function tests (transaminases (AST/ALT), total bilirubin, and alkaline phosphatase) >2X normal values
- Subjects with acutely decompensated heart failure requiring hospitalization or medication adjustment or hospitalization for any cause within the previous 30 days prior to screening
- Subjects may not be receiving any other investigational agents
- Subjects with left ventricular ejection fraction <45% or left ventricular shortening fraction <0.2
- Subjects with acute myocardial infarction within 90 days prior to screening
- Subjects taking nitrates for any medical problem
- Subjects with a recent (<180 days) history of pulmonary embolism verified by ventilation/perfusion scan, angiogram or spiral CT scan
- Pregnant or lactating women
- Subjects with a history of current drug abuse including alcohol
- History of gastric bypass surgery
- History of sinus or atrioventricular nodal disease ie. sick sinus syndrome, or second or third degree heart block.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension
The purpose of this study is to assess the safety of ranolazine in people with pulmonary arterial hypertension (PAH) and who are receiving 1 or more background PAH therapies: ambrisentan, sildenafil,tadalafil, epoprostenol, treprostinil (IV, SC, inhaled), or iloprost. The primary objective is:
- To estimate the effect of ranolazine administration on acute hemodynamics.
- To assess safety of ranolazine acutely over 6 hrs in the catheterization lab and after 12 weeks of therapy
- To assess changes in right ventricular function after 12 weeks of therapy.
Read the detailed description
Pulmonary arterial hypertension is a medical disorder in which pressure in the blood vessels going from the right side of the heart to the lungs is higher than normal. The increased blood pressure in the lungs places a strain on the heart. This strain causes the heart to pump less blood into the lungs, causing physical symptoms of shortness of breath and tiredness. The added strain to the heart can cause physical symptoms of swelling in the feet and abdomen. These symptoms can get worse over time due to the decreased pumping ability of the heart.
This study will use a drug called ranolazine. This drug has been approved by the Food and Drug Administration (FDA) to treat chronic angina (chest pain). However, since it has not been approved for use in PAH its use in this study is considered experimental.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Ranolazine, Placebo
- Keywords
- PAH, Ranolazine, right ventricle, Safety, cardiopulmonary exercise testing
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called GS-9668
ranolazine sustained release at a dose of 500mg for one month followed by a dose of 1000mg.
PlaceboDrug
Also called sugar pill
placebo at a dose of 500mg for one month followed by a dose of 1000mg.
| Study group | Role | What they receive |
|---|---|---|
| Ranolazine | Experimental | Not described Receives: Drug: Ranolazine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pulmonary vascular resistance (PVR)
Measured: 12 weeks
Secondary outcomes (4)
Change in CPET (VE/VCO2, PETCO2, peak VO2, peak HR, peak RER, work max (MET or Watt), sub maximum exercise time
Measured: 12 weeks
Change in RV echo parameters: 2D, 3D
Measured: 12 weeks
Change in 6MWD
Measured: 12 weeks
Safety/SAE
AE and SAE on study drug and acutely changes in blood pressure and PAP
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2012 (estimated)
- Study startAug 2011
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mardi Gomberg-Maitland, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01757808
- Sponsor's protocol ID
- 11-0301
- Status last verified
- Mar 2017
- First submitted
- 26 Apr 2012
- Last updated
- 3 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gomberg-Maitland M, Schilz R, Mediratta A, Addetia K, Coslet S, Thomeas V, Gillies H, Oudiz RJ. Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulm Circ. 2015 Dec;5(4):691-700. doi: 10.1086/683813.
PubMed 26697176
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Ranolazine Acute Administration and Short Term Administration in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01757808
- Acronym / sponsor ID
- 11-0301
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- PAH, Ranolazine, right ventricle, Safety, cardiopulmonary exercise testing
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 31 Dec 2012 (estimated)
- Results
- Not posted in the source record
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 this study is to assess the safety of ranolazine in people with pulmonary arterial hypertension (PAH) and who are receiving 1 or more background PAH therapies: ambrisentan, sildenafil,tadalafil, epoprostenol, treprostinil (IV, SC, inhaled), or iloprost. The primary objective is:
- To estimate the effect of ranolazine administration on acute hemodynamics.
- To assess safety of ranolazine acutely over 6 hrs in the catheterization lab and after 12 weeks of therapy
- To assess changes in right ventricular function after 12 weeks of therapy.
Detailed description
Pulmonary arterial hypertension is a medical disorder in which pressure in the blood vessels going from the right side of the heart to the lungs is higher than normal. The increased blood pressure in the lungs places a strain on the heart. This strain causes the heart to pump less blood into the lungs, causing physical symptoms of shortness of breath and tiredness. The added strain to the heart can cause physical symptoms of swelling in the feet and abdomen. These symptoms can get worse over time due to the decreased pumping ability of the heart.
This study will use a drug called ranolazine. This drug has been approved by the Food and Drug Administration (FDA) to treat chronic angina (chest pain). However, since it has not been approved for use in PAH its use in this study is considered experimental.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranolazine | Experimental | Drug: Ranolazine |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- All subjects age 18-72 yrs will have a diagnosis of PAH. PAH as defined as idiopathic PAH, heritable PAH or PAH associated with collagen vascular disease, congenital heart disease (repaired), or anorexigen use. A history of PAH as defined by hemodynamics at diagnosis by right heart catheterization defined as: mean PAP >25 mmHg with a normal PCWP < 15 mm Hg at rest and a PVR >3 Wood units.
- Baseline 6MW >150 meters
- Patients will be receiving FDA approved PAH monotherapy or dual therapy medications: including, ambrisentan (5,10mg), sildenafil (60-240mg), tadalafil (40mg), epoprostenol, treprostinil, or iloprost at stable doses for >90days.
- Receiving conventional therapy as clinically indicated (oxygen, calcium channel blockers, digoxin) with dose that is unchanged in the preceding 30 days prior to enrollment. This is excluding anticoagulants (warfarin) as the patient's dose may not be stable if the patient is having a cardiac catheterization at baseline within 30 days of enrollment and warfarin is being held.
Key exclusion criteria (22 listed)
- PAH Category II-IV and Category I associated with all other etiologies: HIV, portopulmonary disease
- All subjects on monotherapy calcium blockers as "calcium blocker responders" irrespective of therapy
- All subjects receiving CY3P4 inducer (i.e. bosentan)
- Subjects with pulmonary hypertension due to significant interstitial lung disease, chronic obstructive pulmonary disease, congestive heart failure, valvular heart disease
- Subjects with (World Health Organization (WHO) functional Class I or Class IV
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: GS-9668ranolazine sustained release at a dose of 500mg for one month followed by a dose of 1000mg. | Drug | Ranolazine |
| PlaceboAlso: sugar pillplacebo at a dose of 500mg for one month followed by a dose of 1000mg. | Drug | Placebo |
Primary outcome
Change in pulmonary vascular resistance (PVR)
Time frame: 12 weeks
4 secondary outcomes
Change in CPET (VE/VCO2, PETCO2, peak VO2, peak HR, peak RER, work max (MET or Watt), sub maximum exercise time
Time frame: 12 weeks
Change in RV echo parameters: 2D, 3D
Time frame: 12 weeks
Change in 6MWD
Time frame: 12 weeks
Safety/SAE
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2017.
- Derived from this study: PubMed 26697176Gomberg-Maitland M, Schilz R, Mediratta A, Addetia K, Coslet S, Thomeas V, Gillies H, Oudiz RJ. Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulm Circ. 2015 Dec;5(4):691-700. doi: 10.1086/683813.
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A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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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.
Mardi Gomberg-Maitland, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ranolazine in people with Pulmonary Arterial Hypertension, run by University of Chicago 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 4 inclusion and 22 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 3 Mar 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in pulmonary vascular resistance (PVR) (time frame: 12 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 NCT01757808, 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 3 Mar 2017.