Pulmonary Hypertension Associated With Sickle Cell DiseasePhase 3NCT03055234
Study to Evaluate Efficacy and Safety of Oral Treprostinil in Subjects With Pulmonary Hypertension (PH) Associated With Sickle Cell Disease (SCD)
A Phase 3 study testing Oral Treprostinil in people with Pulmonary Hypertension Associated With Sickle Cell Disease, run by United Therapeutics.
Trial summary
This is a multicenter, randomized (2:1; oral treprostinil:placebo), double-blind, placebo-controlled event-driven (time to pulmonary hypertension [PH] clinical worsening) study in subjects with PH associated with sickle cell disease (SCD). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pulmonary Hypertension Associated With Sickle Cell Disease
- What is being tested?
- Oral Treprostinil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2017to Dec 2022
- Phase
- Phase 3
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The subject must have a diagnosis of SCD confirmed by hemoglobin electrophoresis.
- The subject has a diagnosis of symptomatic World Health Organization (WHO) Group 5.1 chronic hemolytic anemia PH.
- The subject must have a Baseline 6MWD greater than 150 meters, in the absence of a concurrent injury, illness, or other confounding factor.
- The subject has pulmonary function tests conducted within 6 months of Screening or during the Screening period.
- The subject must be on stable doses of other medical therapy for at least 30 days prior to randomization with no dose adjustments, additions, or discontinuations.
- The subject must be optimally treated with conventional PH therapy for at least 10 days prior to randomization with no additions, discontinuations, or dose changes.
- Subjects receiving an endothelin receptor antagonist (ERA) must have been receiving therapy for greater than 90 days, and have reached and maintained a stable dose for a minimum of 30 days prior to randomization.
- Subjects receiving calcium channel blockers must have been on a stable dose for a minimum of 3 months prior to randomization.
Who cannot join
- The subject is pregnant or lactating.
- The subject has previously received oral treprostinil or is receiving a phosphodiesterase type 5 inhibitor (PDE5-I).
- The subject has received a prostacyclin within 30 days prior to start of the study, or had previous intolerance or significant lack of efficacy to any prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to titrate that therapy effectively.
- The subject has had any other background conventional therapies for PH added, removed, or doses adjusted within 10 days prior to randomization.
- The subject has any disease associated with pulmonary arterial hypertension (PAH).
- The subject has had a vaso-occlusive crisis, acute chest syndrome event, or unscheduled transfusion within 30 days of randomization.
Show all 12Show fewer
- The subject has a history of ischemic heart disease, including a previous myocardial infarction or symptomatic coronary artery disease, within 6 months prior to Screening or a left ventricular ejection fraction less than 40% assessed by either multigated angiogram (MUGA), angiography, or echocardiogram.
- The subject has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels 3 times or greater than the upper limit of normal, clinically significant liver disease/dysfunction, or known Child-Pugh Class B or C hepatic disease at Screening.
- The subject has chronic renal insufficiency, as defined by the requirement for dialysis.
- The subject has a musculoskeletal disorder, any disease that is likely to limit ambulation, or is connected to a machine that is not portable.
- The subject has an unstable psychiatric condition or is mentally incapable of understanding the objectives, nature, or consequences of the study, or has any condition which in the Investigator's opinion would constitute an unacceptable risk to the subject's safety.
- The subject is receiving an investigational drug, has an investigational device in place, or has participated in an investigational drug or device study within 30 days prior to Screening.
About this study
Official title: A Phase 3, Multicenter, Randomized, Placebo-controlled Study to Evaluate Efficacy and Safety of Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Sickle Cell Disease
This is a multicenter, randomized (2:1; oral treprostinil:placebo), double-blind, placebo-controlled event-driven (time to pulmonary hypertension [PH] clinical worsening) study in subjects with PH associated with sickle cell disease (SCD). Once enrolled, subjects will be evaluated at Weeks 6, 12, 24, and then every 12 weeks for the duration of the study. Subjects will be permitted to enter a 48-week open-label extension period if they experience a PH clinical worsening event.
- Being tested
- Oral Treprostinil, Placebo
- Keywords
- Oral treprostinil, 6-Minute Walk Distance, PH, sickle cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral TreprostinilDrug
Extended-release oral tablet for TID administration
PlaceboDrug
Matching placebo for TID administration
| Study group | Role | What they receive |
|---|---|---|
| Oral Treprostinil | Experimental | Extended-release oral tablet for three times daily (TID) administration Receives: Drug: Oral Treprostinil |
| Placebo | Placebo comparator | Placebo (sugar pill) for TID administration Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of oral treprostinil compared with placebo on time to first adjudicated PH clinical worsening (morbidity or mortality) event in subjects with PH associated with SCD
Clinical worsening is defined as the occurrence of any 1 of the following events: hospitalization related to PH and/or right heart failure, initiation of an infused prostacyclin to treat worsening PH, decrease in 6-Minute Walk Distance (6MWD) >15% from Baseline directly related to disease under study.
Measured: Baseline until the first adjudicated PH clinical worsening event, assessed up to approximately 4 years
Secondary outcomes (5)
Effect of oral treprostinil compared with placebo on exercise capacity as assessed by 6-Minute Walk Distance (6MWD)
Measured: Baseline to Week 24
Effect of oral treprostinil compared with placebo on combined 6MWD/Borg dyspnea score
Measured: Baseline to Week 24
Effect of oral treprostinil compared with placebo on Borg dyspnea score
Measured: Baseline to Week 24
Effect of oral treprostinil compared with placebo on N-Terminal pro-brain natriuretic peptide (NT-proBNP) levels
Measured: Baseline to Week 24
Effect of oral treprostinil compared with placebo on maximal tricuspid regurgitant velocity (TRV) assessed by transthoracic Doppler echocardiography
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2017
- Study startJun 2017 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionDec 2022 (estimated)
Why it stopped: Business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Hypertension Associated With Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by United TherapeuticsThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03055234
- Sponsor's protocol ID
- TDE-SC-301
- Status last verified
- Apr 2017
- First submitted
- 27 Jan 2017
- Last updated
- 11 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- 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 11 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Placebo-controlled Study to Evaluate Efficacy and Safety of Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT03055234
- Acronym / sponsor ID
- TDE-SC-301
- Keywords
- Oral treprostinil, 6-Minute Walk Distance, PH, sickle cell
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Business decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2017 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 16 Feb 2017 (actual)
- 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.
This is a multicenter, randomized (2:1; oral treprostinil:placebo), double-blind, placebo-controlled event-driven (time to pulmonary hypertension [PH] clinical worsening) study in subjects with PH associated with sickle cell disease (SCD). Once enrolled, subjects will be evaluated at Weeks 6, 12, 24, and then every 12 weeks for the duration of the study. Subjects will be permitted to enter a 48-week open-label extension period if they experience a PH clinical worsening event.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Treprostinil | Experimental | Drug: Oral TreprostinilExtended-release oral tablet for three times daily (TID) administration |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (sugar pill) for TID administration |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- The subject must have a diagnosis of SCD confirmed by hemoglobin electrophoresis.
- The subject has a diagnosis of symptomatic World Health Organization (WHO) Group 5.1 chronic hemolytic anemia PH.
- The subject must have a Baseline 6MWD greater than 150 meters, in the absence of a concurrent injury, illness, or other confounding factor.
- The subject has pulmonary function tests conducted within 6 months of Screening or during the Screening period.
- The subject must be on stable doses of other medical therapy for at least 30 days prior to randomization with no dose adjustments, additions, or discontinuations.
Key exclusion criteria (12 listed)
- The subject is pregnant or lactating.
- The subject has previously received oral treprostinil or is receiving a phosphodiesterase type 5 inhibitor (PDE5-I).
- The subject has received a prostacyclin within 30 days prior to start of the study, or had previous intolerance or significant lack of efficacy to any prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to titrate that therapy effectively.
- The subject has had any other background conventional therapies for PH added, removed, or doses adjusted within 10 days prior to randomization.
- The subject has any disease associated with pulmonary arterial hypertension (PAH).
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 |
|---|---|---|
| Oral TreprostinilExtended-release oral tablet for TID administration | Drug | Oral Treprostinil |
| PlaceboMatching placebo for TID administration | Drug | Placebo |
Primary outcome
Effect of oral treprostinil compared with placebo on time to first adjudicated PH clinical worsening (morbidity or mortality) event in subjects with PH associated with SCD
Time frame: Baseline until the first adjudicated PH clinical worsening event, assessed up to approximately 4 years
Clinical worsening is defined as the occurrence of any 1 of the following events: hospitalization related to PH and/or right heart failure, initiation of an infused prostacyclin to treat worsening PH, decrease in 6-Minute Walk Distance (6MWD) >15% from Baseline directly related to disease under study.
5 secondary outcomes
Effect of oral treprostinil compared with placebo on exercise capacity as assessed by 6-Minute Walk Distance (6MWD)
Time frame: Baseline to Week 24
Effect of oral treprostinil compared with placebo on combined 6MWD/Borg dyspnea score
Time frame: Baseline to Week 24
Effect of oral treprostinil compared with placebo on Borg dyspnea score
Time frame: Baseline to Week 24
Effect of oral treprostinil compared with placebo on N-Terminal pro-brain natriuretic peptide (NT-proBNP) levels
Time frame: Baseline to Week 24
Effect of oral treprostinil compared with placebo on maximal tricuspid regurgitant velocity (TRV) assessed by transthoracic Doppler echocardiography
Time frame: Baseline to Week 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2017.
- Individual participant dataSharing planned: No
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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oral Treprostinil in people with Pulmonary Hypertension Associated With Sickle Cell Disease, run by United Therapeutics.
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 12 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: withdrawn, as of the sponsor's last update on 11 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
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 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Effect of oral treprostinil compared with placebo on time to first adjudicated PH clinical worsening (morbidity or mortality) event in subjects with PH associated with SCD (time frame: Baseline until the first adjudicated PH clinical worsening event, assessed up to approximately 4 years). 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 11 Apr 2017.