Pulmonary Arterial HypertensionPhase 4T2NCT01302444
Treprostinil Combined With Tadalafil for Pulmonary Hypertension
A Phase 4 study testing Tadalafil in people with Pulmonary Arterial Hypertension, run by Rhode Island Hospital at 9 sites in United States.
Trial summary
Objectives: To test whether the combined administration of the medications treprostinil(a prostacycline therapy), and tadalafil(a PDE-5 [ phosphodiesterase type 5]Inhibitor therapy) is better than the administration of treprostinil alone. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Tadalafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 9 sitesUnited States
- Study dates
- Mar 2011to Mar 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients 18-80 years of age
- World Health Organization Group 1 PAH
- Idiopathic PAH
- Heritable PAH
- PAH associated with connective tissue disease
- PAH associated with surgical repair of congenital left to right shunt
Show all 10Show fewer
- PAH associated with anorectic drug use
- WHO functional Class III-IV
- 6 minute walking distance > 150-meters and < 450 meters
- Right heart catheterization showing mean PAP (pulmonary arterial pressure)> 25 mmHg and PCWP (pulmonary capillary wedge pressure) < 15 mmHg within 6 months of study entry.
Who cannot join
- Pulmonary hypertension associated with
- Portal hypertension b. HIV infection c. Pulmonary venous hypertension defined as PCWP > 15 mmHg d. Chronic lung disease defined as i. FEV1(forced expiratory volume at one second
- )/FVC (forced vital capacity) less than 0.65 ii. TLC < 0.70 iii. Untreated Sleep Apnea with AHI (apnea-hypopnea index )> 20 or hemoglobin oxygen saturation nadir < 87% e. Chronic Thromboembolic Disease f. Sarcoidosis g. Pulmonary veno occlusive disease (PVOD)
- Concomitant use of nitrates (any form) either regularly or intermittently.
- Concomitant use of potent CYP3A inhibitors (e.g., ritonavir, ketoconazole, itraconazole)
- Vascular disease of the retina including retinitis pigmentosa, any sudden vision loss, including any damage to the optic nerve or NAION
Show all 20Show fewer
- low blood pressure or high blood pressure that is not controlled
- Postural hypotension
- Inability to manage home infusion therapy
- Pulmonary vasodilator therapy with any phosphodiesterase inhibitor or endothelin receptor antagonist within 30 days of study entry
- Participation in a clinical investigational study within previous 30 days
- Renal failure defined as:
- estimated creatinine clearance < 30 ml/min
- serum creatinine > 2.5 mg/dl
- Subjects with liver function abnormalities (ALT [Alanine Aminotransferase or AST (Alanine Aminotransferase ) > 3 times the upper limit of normal at screening or at baseline) or chronic liver disease
- History of hypersensitivity reaction or adverse effect related to tadalafil
- Life expectancy < 12 months
- History of deformed penis shape, an erection that lasted more than 4 hours, or Peyronie's disease.
- Blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia
- Pregnant or planning to become pregnant or breast feed.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Tuft's New England Medical Center
Boston, Massachusetts, 02111
Brigham & Womens Hospital
Boston, Massachusetts, 02115
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Beth Israel Medical Center
New York, New York, 10003
Weill Cornell Medical Center
New York, New York, 10021
Saint Barnabas Health Care System, Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Maine Medical Center
Portland, Maine, 04102
Rhode Island Hospital
Providence, Rhode Island, 02903
University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: Randomized Placebo Controlled Trial of Treprostinil Infusion Combined With Oral Tadalafil or Placebo in Pulmonary Arterial Hypertension
Objectives: To test whether the combined administration of the medications treprostinil(a prostacycline therapy), and tadalafil(a PDE-5 [ phosphodiesterase type 5]Inhibitor therapy) is better than the administration of treprostinil alone. This treatment would be offered to newly diagnosed patients with pulmonary arterial hypertension who are on no treatment for this disease and are deemed candidates for the medication treprostinil by their physician. The combination therapy will be compared to single therapy with only treprostinil in a double-blind manner.
Current therapy is to begin one treatment, either a PDE5 inhibitor or a prostacycline, depending on the severity of the patient's PAH (pulmonary arterial hypertension) disease and add additional therapies as deterioration occurs. This treatment could add two agents initially.
Read more
Secondary objectives are: To improve pulmonary arterial pressures as measured through a cardiac echocardiogram, improve the subject's 6minute walk distance, delaying the time to clinical worsening, and lowering plasma BNP levels.
Research Procedures: To begin the administration of both treatments at the same time.
Time period is 16 weeks with a one- year follow-up. Cardiac Echocardiograms, clinic physician exams, and lab work will be followed. Subjects will be between the ages of 18 - 75.
Read the detailed description
Background: Many cardiovascular diseases such as essential hypertension, coronary artery disease and congestive heart failure respond better to combinations of vasoactive drugs, than to therapy with a single agent. Three categories of pulmonary anti-hypertensive medications have been developed over the last 20 years, but their effect on management of PAH when used in combination are mostly unknown. Two of the pulmonary arterial hypertension (PAH) drug groups are prostacyclines, and PDE5 inhibitors. Although the effects of prostacyclins are mediated via cAMP (cyclic guanosine monophosphate) and the effects of PDE5 inhibitors are mediated via cGMP, there is considerable cross talk between these nucleotides suggesting that adequate levels of both may be needed to maintain normal pulmonary vascular tone and cellular growth responses.
Objective/Hypothesis: This proposal hypothesizes that increasing the levels of both nucleotides (prostacyclines and PDE5 inhibitors), may be more efficacious in the treatment of PAH than increasing either one alone.
Specific Aims: The primary objective of this study is to determine if the combination of treprostinil infusion combined with tadalafil is more efficacious than treprostinil alone in improving the change from baseline in the 6 minute walking distance after 16 weeks of therapy.
Study Design: The proposed study is a multi-center, randomized, double blind, two cohort, parallel group, and 16-week study with 1-year long-term follow-up. The study aims to compare the efficacy of combination therapy with treprostinil infusion and tadalafil to treprostinil infusion alone.
Study Population: All patients who have been newly diagnosed with PAH and who, after consultation with their physician, have elected to be treated with treprostinil infusion will be invited to participate. A total of 66 subjects will be sort to enroll.
Treprostinil dosing will follow a 4 week up-titration schedule with a target 4week dose of 8ng/kg/min minimum, followed by a 12 week randomized tadalafil period.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Tadalafil, Placebo
- Keywords
- treprostinil, pulmonary hypertension, tadalafil
- Medical subject headings
- Pulmonary Arterial Hypertension, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Adcirca
Tadalafil 40mg for 12 weeks
PlaceboDrug
Also called sugar pill
Placebo for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Tadalafil | Active comparator | first 4 weeks are for adjusting treprostinil dose, then Tadalafil 40mg daily for 12 weeks, Group is randomly chosen from entire cohort Receives: Drug: Tadalafil |
| Placebo | Placebo comparator | first 4 weeks for adjusting treprostinil dose, then Placebo for 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
All Cause Mortality
Measured: 16 weeks
Adverse Events Are no Greater Than With Treprostinil Infusion Alone
Measured: 16 weeks
WHO Functional Class Will Improve or Remain Stable
Measured: 16 weeks
Hospitalizations
Measured: 16 weeks
Secondary outcomes (4)
6 Minute Walking Distance Change Will Improve
Measured: 16 weeks of therapy
Tei Index Change by Transthoracic Echocardiography
Measured: 16 weeks of therapy
Plasma BNP (Brain Natriuretic Peptide)Level Change
Measured: 16 weeks of therapy
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP)as Assessed by Transthoracic Echocardiography Using Doppler Ultrasound
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2011 (estimated)
- Study startMar 2011
- Primary completionMar 2012
- Study completionMar 2012
Why it stopped: One subject enrolled and completed this study. The study was stopped due to poor recruitment.
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 Arterial HypertensionStudies of the same condition, open and under way.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rhode Island Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- United Therapeutics
- Responsible party
- Sponsor
- Investigators
- James R Klinger, MD, Study director, Rhode Island Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01302444
- Sponsor's protocol ID
- T2 Trial
- Acronym
- T2
- Status last verified
- Apr 2012
- First submitted
- 16 Feb 2011
- Last updated
- 26 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo Controlled Trial of Treprostinil Infusion Combined With Oral Tadalafil or Placebo in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01302444
- Acronym / sponsor ID
- T2 / T2 Trial
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- treprostinil, pulmonary hypertension, tadalafil
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: One subject enrolled and completed this study. The study was stopped due to poor recruitment.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Rhode Island HospitalUniversity, hospital or other
- Collaborators
- United Therapeutics
- Study start
- Mar 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 24 Feb 2011 (estimated)
- Results
- Posted 18 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives: To test whether the combined administration of the medications treprostinil(a prostacycline therapy), and tadalafil(a PDE-5 [ phosphodiesterase type 5]Inhibitor therapy) is better than the administration of treprostinil alone. This treatment would be offered to newly diagnosed patients with pulmonary arterial hypertension who are on no treatment for this disease and are deemed candidates for the medication treprostinil by their physician. The combination therapy will be compared to single therapy with only treprostinil in a double-blind manner.
Current therapy is to begin one treatment, either a PDE5 inhibitor or a prostacycline, depending on the severity of the patient's PAH (pulmonary arterial hypertension) disease and add additional therapies as deterioration occurs. This treatment could add two agents initially.
Secondary objectives are: To improve pulmonary arterial pressures as measured through a cardiac echocardiogram, improve the subject's 6minute walk distance, delaying the time to clinical worsening, and lowering plasma BNP levels.
Research Procedures: To begin the administration of both treatments at the same time.
Time period is 16 weeks with a one- year follow-up. Cardiac Echocardiograms, clinic physician exams, and lab work will be followed. Subjects will be between the ages of 18 - 75.
Detailed description
Background: Many cardiovascular diseases such as essential hypertension, coronary artery disease and congestive heart failure respond better to combinations of vasoactive drugs, than to therapy with a single agent. Three categories of pulmonary anti-hypertensive medications have been developed over the last 20 years, but their effect on management of PAH when used in combination are mostly unknown. Two of the pulmonary arterial hypertension (PAH) drug groups are prostacyclines, and PDE5 inhibitors. Although the effects of prostacyclins are mediated via cAMP (cyclic guanosine monophosphate) and the effects of PDE5 inhibitors are mediated via cGMP, there is considerable cross talk between these nucleotides suggesting that adequate levels of both may be needed to maintain normal pulmonary vascular tone and cellular growth responses.
Objective/Hypothesis: This proposal hypothesizes that increasing the levels of both nucleotides (prostacyclines and PDE5 inhibitors), may be more efficacious in the treatment of PAH than increasing either one alone.
Specific Aims: The primary objective of this study is to determine if the combination of treprostinil infusion combined with tadalafil is more efficacious than treprostinil alone in improving the change from baseline in the 6 minute walking distance after 16 weeks of therapy.
Study Design: The proposed study is a multi-center, randomized, double blind, two cohort, parallel group, and 16-week study with 1-year long-term follow-up. The study aims to compare the efficacy of combination therapy with treprostinil infusion and tadalafil to treprostinil infusion alone.
Study Population: All patients who have been newly diagnosed with PAH and who, after consultation with their physician, have elected to be treated with treprostinil infusion will be invited to participate. A total of 66 subjects will be sort to enroll.
Treprostinil dosing will follow a 4 week up-titration schedule with a target 4week dose of 8ng/kg/min minimum, followed by a 12 week randomized tadalafil period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tadalafil | Active comparator | Drug: Tadalafilfirst 4 weeks are for adjusting treprostinil dose, then Tadalafil 40mg daily for 12 weeks, Group is randomly chosen from entire cohort |
| Placebo | Placebo comparator | Drug: Placebofirst 4 weeks for adjusting treprostinil dose, then Placebo for 12 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult patients 18-80 years of age
- World Health Organization Group 1 PAH
- WHO functional Class III-IV
- 6 minute walking distance > 150-meters and < 450 meters
- Right heart catheterization showing mean PAP (pulmonary arterial pressure)> 25 mmHg and PCWP (pulmonary capillary wedge pressure) < 15 mmHg within 6 months of study entry.
Key exclusion criteria (20 listed)
- Pulmonary hypertension associated with
- )/FVC (forced vital capacity) less than 0.65 ii. TLC < 0.70 iii. Untreated Sleep Apnea with AHI (apnea-hypopnea index )> 20 or hemoglobin oxygen saturation nadir < 87% e. Chronic Thromboembolic Disease f. Sarcoidosis g. Pulmonary veno occlusive disease (PVOD)
- Concomitant use of nitrates (any form) either regularly or intermittently.
- Concomitant use of potent CYP3A inhibitors (e.g., ritonavir, ketoconazole, itraconazole)
- Vascular disease of the retina including retinitis pigmentosa, any sudden vision loss, including any damage to the optic nerve or NAION
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 |
|---|---|---|
| TadalafilAlso: AdcircaTadalafil 40mg for 12 weeks | Drug | Tadalafil |
| PlaceboAlso: sugar pillPlacebo for 12 weeks | Drug | Placebo |
Primary outcome
All Cause Mortality
Time frame: 16 weeks
Adverse Events Are no Greater Than With Treprostinil Infusion Alone
Time frame: 16 weeks
WHO Functional Class Will Improve or Remain Stable
Time frame: 16 weeks
Hospitalizations
Time frame: 16 weeks
4 secondary outcomes
6 Minute Walking Distance Change Will Improve
Time frame: 16 weeks of therapy
Tei Index Change by Transthoracic Echocardiography
Time frame: 16 weeks of therapy
Plasma BNP (Brain Natriuretic Peptide)Level Change
Time frame: 16 weeks of therapy
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP)as Assessed by Transthoracic Echocardiography Using Doppler Ultrasound
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- treprostinilLink 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.
James R Klinger, MD study director
Rhode Island Hospital
9 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 Tadalafil in people with Pulmonary Arterial Hypertension, run by Rhode Island Hospital at 9 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 10 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: stopped early, as of the sponsor's last update on 26 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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. 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 18 Jul 2013). 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?
All Cause Mortality (time frame: 16 weeks). The study lists 4 primary outcomes in all. 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 26 Jul 2013.