Hypertension, PulmonaryPhase 4NCT01305252
A 48-week Study of the Effect of Dual Therapy (Inhaled Treprostinil and Tadafafil) Versus Monotherapy (Tadalafil).
A Phase 4 study testing treprostinil inhalations and tadalafil in people with Hypertension, Pulmonary, run by Stanford University at 2 sites in United States.
Trial summary
The Study Hypothesis: Aggressive, upfront, dual therapy for treatment-naïve NYHA I/II/III PAH is superior to a traditional "step-up" approach. The study will evaluate: 1. Impact of dual, upfront, therapy on cardiovascular parameters in PAH as gauged by cardiac magnetic resonance imaging (cMRI) at 24 weeks and event… Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Hypertension, Pulmonary
- What is being tested?
- treprostinil inhalations and tadalafil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2010to Sep 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 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 and < 75 years at baseline visit.
- Diagnosis of Idiopathic PAH, Heritable PAH (including Hereditary Hemorrhagic Telangiectasia), Associated PAH (including collagen vascular disorders, drug+toxin exposure, repaired congenital heart disease repaired > 5 years, portopulmonary disease, and human immunodeficiency virus (HIV) infection not on protease inhibitor).
- PAH treatment naïve including any prostacycline, endothelin receptor antagonist, or phosphodiesterase inhibitors within 12 months prior to enrollment.
- Previous Right Heart Catheterization that documented:
- Mean PAP; 25 mmHg.
- Pulmonary capillary wedge pressure < 15 mmHg.
- Pulmonary Vascular Resistance; 3.0 Wood units or 240 dynes/sec/cm5 5.6MW distances; 150 m and < 450 meters.
- 6. WHO functional class II or III as judged by principal investigators.
Who cannot join
- Group II - V pulmonary hypertension.
- PAH with unrepaired congenital heart defect.
- Current or prior PAH treatments within the last 6-12 months including experimental PAH therapies (including but not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, phosphodiesterase inhibitors, prostacycline, or cGMP modulators).
- TLC < 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed tomography must be available to exclude significant interstitial lung disease.
- FEV1 / FVC < 70% predicted and FEV1 < 60% predicted
- Significant left-sided heart disease (based on pre-trial Echocardiogram):
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- Significant aortic or mitral valve disease
- Diastolic dysfunction ; Grade II C.LV systolic function < 45%
- Pericardial constriction e. Restrictive cardiomyopathy f. Significant coronary disease with demonstrable ischemia
- Chronic renal insufficiency defined as an estimated creatinine clearance < 30 ml/min (by MDRD equation)
- Current atrial arrhythmias
- Uncontrolled systemic hypertension: SBP > 160 mm or DBP > 100mm
- Severe hypotension: SBP < 80 mmHg.
- Pregnant or breast-feeding
- Psychiatric, addictive, or other disorder that compromises patient's ability to provide informed consent, follow study protocol, and adhere to treatment instructions
- Co-morbid conditions that would impair a patient's exercise performance and ability to assess WHO functional class, including but not limited to chronic low-back pain or peripheral musculoskeletal problems.
- Contraindications for magnetic resonance imaging, including significant claustrophobia, implanted metallic objects, or others as per Appendix X).
- Known allergy to treprostinil or tadalafil.
- Active oral nitrate use.
- Diabetes mellitus.
- Planned initiation of cardiac or pulmonary rehabilitation during period of study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern University
Chicago, Illinois, 60208
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: CombinatiON Up-FRON t Therapy for PAH - A Phase 4, Randomized, Multicenter Study of Inhaled Treprostinil in Treatment naïve Pulmonary Arterial Hypertension Patients Starting on Tadalafil
The Study Hypothesis:
Aggressive, upfront, dual therapy for treatment-naïve NYHA I/II/III PAH is superior to a traditional "step-up" approach.
The study will evaluate:
- Impact of dual, upfront, therapy on cardiovascular parameters in PAH as gauged by cardiac magnetic resonance imaging (cMRI) at 24 weeks and event free survival at outcome at 48 weeks.
- Value of novel biomarkers (NT-pro BNP, Mts1/S100A4, and insulin resistance) and cutting-edge imaging technologies (cardiac MRI) as newer endpoints for clinical trials in PAH.
- Utility of longer clinical trial design with the use of combined clinical events as time to clinical worsening surrogate
Read the detailed description
This is a 48 week interventional study evaluating the effect of Dual therapy ( Treprostinil inhalations and Tadalafil) versus Mono therapy (Tadalafil). The impact of the therapy on cardiovascular parameters in PAH measured at 24 weeks and event free survival outcome at 48 weeks.
- Conditions
- Hypertension, Pulmonary
- Being tested
- treprostinil inhalations, tadalafil
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
treprostinil inhalationsDrug
Also called Tyvaso
Treprostinil inhalation QID starting at 3 breaths per inhalation \& gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.
tadalafilDrug
Also called Adcirca
tadalafil 20mg QD PO increasing to 40mg QD as tolerated
| Study group | Role | What they receive |
|---|---|---|
| tadalafil alone | Active comparator | tadalafil 40mg QD(Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated). Receives: Drug: tadalafil |
| tadalafil and treprostinil inhalations | Active comparator | Treprostinil inhalation QID starting at 3 breaths per inhalation \& gradually increasing to 9 breaths.Each breath provides approximately 6 mcg of treprostinil.Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated. Receives: Drug: treprostinil inhalations; Drug: tadalafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Right Ventricular Ejection Fraction
Effect of dual-upfront therapies versus mono-therapy on percent change of right ventricular function assesed by cardiac MRI (cMRI) at 24 weeks compared with the baseline.
Measured: Basline and 24 weeks
Secondary outcomes (4)
6 Minute Walk Distance
Change in 6MWD during 24 week period compared between Tada and Tada+iTre.
Measured: Baseline and 24 weeks
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Change from baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Measured: Baseline and 24 weeks
Change in NYHA/WHO Class
At 48 week,WHO/NYHA functional class was assessed for change in WHO/NYHA functional class.Change NYHA is measured as decrease or increase in NYHA class in the subjects compared with baseline.
NYHA /WHO functional class is described below:
NYHA functional class I:no symptoms and no limitation in ordinary physical activity NYHA functional class II:Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity NYHA functional class III:Marked limitation in activity due to symptoms, even during less-than-ordinary activity NYHA functional class IV:Severe limitations. Experiences symptoms even while at rest A higher functional class represent worse symptoms.
Measured: Baseline and 48 week
B-type Natriuretic Peptide (BNP)
B-type Natriuretic peptide measures the percent change from baseline.
Measured: Baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2011 (estimated)
- Study startJul 2010
- Primary completionSep 2014
- Study completionSep 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 Hypertension, PulmonaryStudies of the same condition, open and under way.
- More trials run by Stanford 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern University
- Responsible party
- Principal investigator, Roham T. Zamanian, Stanford University
- Investigators
- Roham T. Zamanian, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01305252
- Sponsor's protocol ID
- SU-07152010-6565
- Other IDs
- IRB protocol # 18305
- Status last verified
- Apr 2017
- First submitted
- 2 Nov 2010
- Last updated
- 2 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CombinatiON Up-FRON t Therapy for PAH - A Phase 4, Randomized, Multicenter Study of Inhaled Treprostinil in Treatment naïve Pulmonary Arterial Hypertension Patients Starting on Tadalafil
- ClinicalTrials.gov ID
- NCT01305252
- Acronym / sponsor ID
- SU-07152010-6565
- Conditions
- Hypertension, Pulmonary
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Northwestern University
- Study start
- Jul 2010
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 28 Feb 2011 (estimated)
- Results
- Posted 2 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Study Hypothesis:
Aggressive, upfront, dual therapy for treatment-naïve NYHA I/II/III PAH is superior to a traditional "step-up" approach.
The study will evaluate:
- Impact of dual, upfront, therapy on cardiovascular parameters in PAH as gauged by cardiac magnetic resonance imaging (cMRI) at 24 weeks and event free survival at outcome at 48 weeks.
- Value of novel biomarkers (NT-pro BNP, Mts1/S100A4, and insulin resistance) and cutting-edge imaging technologies (cardiac MRI) as newer endpoints for clinical trials in PAH.
- Utility of longer clinical trial design with the use of combined clinical events as time to clinical worsening surrogate
Detailed description
This is a 48 week interventional study evaluating the effect of Dual therapy ( Treprostinil inhalations and Tadalafil) versus Mono therapy (Tadalafil). The impact of the therapy on cardiovascular parameters in PAH measured at 24 weeks and event free survival outcome at 48 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tadalafil alone | Active comparator | Drug: tadalafiltadalafil 40mg QD(Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated). |
| tadalafil and treprostinil inhalations | Active comparator | Drug: treprostinil inhalations, Drug: tadalafilTreprostinil inhalation QID starting at 3 breaths per inhalation \& gradually increasing to 9 breaths.Each breath provides approximately 6 mcg of treprostinil.Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 and < 75 years at baseline visit.
- Diagnosis of Idiopathic PAH, Heritable PAH (including Hereditary Hemorrhagic Telangiectasia), Associated PAH (including collagen vascular disorders, drug+toxin exposure, repaired congenital heart disease repaired > 5 years, portopulmonary disease, and human immunodeficiency virus (HIV) infection not on protease inhibitor).
- PAH treatment naïve including any prostacycline, endothelin receptor antagonist, or phosphodiesterase inhibitors within 12 months prior to enrollment.
- Previous Right Heart Catheterization that documented:
- 6. WHO functional class II or III as judged by principal investigators.
Key exclusion criteria (21 listed)
- Group II - V pulmonary hypertension.
- PAH with unrepaired congenital heart defect.
- Current or prior PAH treatments within the last 6-12 months including experimental PAH therapies (including but not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, phosphodiesterase inhibitors, prostacycline, or cGMP modulators).
- TLC < 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed tomography must be available to exclude significant interstitial lung disease.
- FEV1 / FVC < 70% predicted and FEV1 < 60% predicted
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 |
|---|---|---|
| treprostinil inhalationsAlso: TyvasoTreprostinil inhalation QID starting at 3 breaths per inhalation \& gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil. | Drug | tadalafil and treprostinil inhalations |
| tadalafilAlso: Adcircatadalafil 20mg QD PO increasing to 40mg QD as tolerated | Drug | tadalafil alone, tadalafil and treprostinil inhalations |
Primary outcome
Change in Right Ventricular Ejection Fraction
Time frame: Basline and 24 weeks
Effect of dual-upfront therapies versus mono-therapy on percent change of right ventricular function assesed by cardiac MRI (cMRI) at 24 weeks compared with the baseline.
4 secondary outcomes
6 Minute Walk Distance
Time frame: Baseline and 24 weeks
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Time frame: Baseline and 24 weeks
Change in NYHA/WHO Class
Time frame: Baseline and 48 week
B-type Natriuretic Peptide (BNP)
Time frame: Baseline and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Roham T. Zamanian principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing treprostinil inhalations and tadalafil in people with Hypertension, Pulmonary, run by Stanford University at 2 sites 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 8 inclusion and 21 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 2 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 2 Jun 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?
Change in Right Ventricular Ejection Fraction (time frame: Basline and 24 weeks). 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 2 Jun 2017.