Pulmonary HypertensionPhase 4NCT00840463
Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan
A Phase 4 study testing Ambrisentan in people with Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
This is a randomized study of ambrisentan that will last 16 weeks. The study will include patients with diastolic heart failure and pulmonary hypertension. Patients will be randomized (1:1) to ambrisentan or placebo. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Ambrisentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Jan 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Catheterization
- Elevated pulmonary arterial pressure (PA mean >25mmHg)
- Elevated pulmonary vascular resistance (>240 dynes.cm.sec-5) or transpulmonary gradient (>12 mmHg)
- Elevated LVEDP (>15mmHg, but ≤23 mmHg)
- Evidence of left ventricular diastolic dysfunction: LA>4.0, LVH or diastolic dysfunction by mitral filling pattern
- Echocardiogram: Normal or mildly reduced LV ejection fraction (greater than or equal to 40%)
Show all 10Show fewer
- Symptomatic chronic HF (WHO functional class II-IV)
- Baseline walk distance 100 to 400 meters
- Age 18 - 80 (increased from 70)
- Maximal treatment of diastolic dysfunction as noted by the treating physicians with no change in medical therapy for one month prior to entry
Who cannot join
- Use of endothelin receptor antagonist, prostacyclin or PDE-5 inhibitor within 4 weeks of enrollment
- Exercise capacity limited by other illness (other lung disease, arthritis, mobility limitations)
- Uncontrolled systemic hypertension
- Uncontrolled atrial fibrillation
- Severe valvular disease
- Pregnant females- females of child bearing potential will need to use contraceptive agent barrier given the teratogenicity associated with ERA's
- Uncontrolled OSA
Trial locations and contacts
1 site in 1 country.
United States1 site
UT Southwestern Medical Center
Dallas, Texas, 75390-8550
About this study
Official title: Safety and Efficacy Trial Using Ambrisentan for Pulmonary Hypertension Associated With Congestive Heart Failure With Preserved Left Ventricular Ejection Fraction
This is a randomized study of ambrisentan that will last 16 weeks. The study will include patients with diastolic heart failure and pulmonary hypertension. Patients will be randomized (1:1) to ambrisentan or placebo. The ambrisentan or matching placebo will be started at 2.5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated. Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and the required monthly laboratory tests (liver function testing and pregnancy testing, if applicable), will be performed. Patients will also complete an exercise test (six minute walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An echocardiogram and a right heart catheterization and left ventricular end diastolic pressure measurement will be performed at the 16 week visit. The primary end-point is safety, and secondary end-points include the catheterization results, echocardiogram results, the walk distance and the quality of life survey. The expected completion of the study is 18 months from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
Read the detailed description
Hypothesis: patients with pulmonary hypertension secondary to diastolic congestive heart failure (CHF) treated with ambrisentan for 16 weeks will have improved hemodynamics, increased exercise capacity and improved functional class with an acceptable safety profile, compared with placebo treated patients.
Objectives: to evaluate the safety and efficacy of ambrisentan treatment in patients with pulmonary hypertension due to diastolic CHF. Efficacy will be assessed by improvement in hemodynamics (PVR(Pulmonary Vascular Resistance): primary efficacy endpoint), six minute walk distance (6MWD), World Health Organization (WHO) functional class and quality of life after 16 weeks of treatment with ambrisentan. Safety of ambrisentan will be compared to placebo.
Concomitant Medication: Treatment with standard medications for CHF including diuretics and optimal blood pressure control with antihypertensive medications will be allowed throughout the study period. Diuretics adjustment will also be allowed and encouraged based on the planned diuretic management protocol. Approved medications for CHF in general are allowed as well, though it should be noted that there are no medications shown to have benefit in diastolic CHF. Patients may not be on an endothelin antagonist or sildenafil.
- Being tested
- Ambrisentan, Placebo
- Keywords
- Pulmonary Hypertension, Diastolic Heart Failure
- Medical subject headings
- Hypertension, Pulmonary, Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
Also called Letairis
Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).
PlaceboOther
Also called The placebo will look identical to the Ambrisentan tablets
Sugar pill
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Not described Receives: Drug: Ambrisentan |
| 2 | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulmonary Vascular Resistance (Wood Units)
The primary efficacy outcome will be Pulmonary Vascular Resistance.PVR will be calculated as [(PA mean - wedge) / Cardiac Output]
Measured: Baseline and Four months
Safety Assessment-Number of Subjects Who Are Free and Those Who Developed Clinically Significant Adverse Events (CSAEs)
Freedom from clinically significant adverse events will be measure by determining the number free from CSAEs and those who developed CSAEs
Measured: 4 months
Secondary outcomes (3)
Change in 6 Minute Walk Distance
subjects complete the 6 minute walk test to determine how far (in meters) they are able to walk in 6 minutes.
Measured: Baseline and Four months
Change in Functional Class
Change in functional class from baseline to month 4. This is graded from WHO FC I to FC IV. Assessment will be completed by an investigator on the study at every visit.
Measured: basline and 4 months
Change in Short Form-36 Physical Functioning
Change between baseline and follow-up in the physical functioning items of the SF-36 questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health
Measured: baseline 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionSep 2013
- Study completionJan 2014
Why it stopped: Poor enrolment
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 University of Texas Southwestern Medical CenterThe 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Kelly M Chin, MD, Principal investigator, University of Texas Southwestern Medical CenterFernando Torres, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00840463
- Sponsor's protocol ID
- IN-US-300-0126
- Status last verified
- May 2020
- First submitted
- 6 Feb 2009
- Last updated
- 19 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy Trial Using Ambrisentan for Pulmonary Hypertension Associated With Congestive Heart Failure With Preserved Left Ventricular Ejection Fraction
- ClinicalTrials.gov ID
- NCT00840463
- Acronym / sponsor ID
- IN-US-300-0126
- Keywords
- Pulmonary Hypertension, Diastolic Heart Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor enrolment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Jan 2009
- Primary completion
- Sep 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 10 Feb 2009 (estimated)
- Results
- Posted 22 May 2019
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 randomized study of ambrisentan that will last 16 weeks. The study will include patients with diastolic heart failure and pulmonary hypertension. Patients will be randomized (1:1) to ambrisentan or placebo. The ambrisentan or matching placebo will be started at 2.5 mg by mouth daily and increased to 5mg and then 10mg daily, if tolerated. Patients will be seen at least monthly for 16 weeks. Adverse reactions will be reviewed and the required monthly laboratory tests (liver function testing and pregnancy testing, if applicable), will be performed. Patients will also complete an exercise test (six minute walk distance) and a quality of life survey at the baseline, week 4 and week 16 visit. An echocardiogram and a right heart catheterization and left ventricular end diastolic pressure measurement will be performed at the 16 week visit. The primary end-point is safety, and secondary end-points include the catheterization results, echocardiogram results, the walk distance and the quality of life survey. The expected completion of the study is 18 months from initiation. Ambrisentan is an FDA approved drug for PAH, but not for CHF.
Detailed description
Hypothesis: patients with pulmonary hypertension secondary to diastolic congestive heart failure (CHF) treated with ambrisentan for 16 weeks will have improved hemodynamics, increased exercise capacity and improved functional class with an acceptable safety profile, compared with placebo treated patients.
Objectives: to evaluate the safety and efficacy of ambrisentan treatment in patients with pulmonary hypertension due to diastolic CHF. Efficacy will be assessed by improvement in hemodynamics (PVR(Pulmonary Vascular Resistance): primary efficacy endpoint), six minute walk distance (6MWD), World Health Organization (WHO) functional class and quality of life after 16 weeks of treatment with ambrisentan. Safety of ambrisentan will be compared to placebo.
Concomitant Medication: Treatment with standard medications for CHF including diuretics and optimal blood pressure control with antihypertensive medications will be allowed throughout the study period. Diuretics adjustment will also be allowed and encouraged based on the planned diuretic management protocol. Approved medications for CHF in general are allowed as well, though it should be noted that there are no medications shown to have benefit in diastolic CHF. Patients may not be on an endothelin antagonist or sildenafil.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Ambrisentan |
| 2 | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Catheterization
- Evidence of left ventricular diastolic dysfunction: LA>4.0, LVH or diastolic dysfunction by mitral filling pattern
- Echocardiogram: Normal or mildly reduced LV ejection fraction (greater than or equal to 40%)
- Symptomatic chronic HF (WHO functional class II-IV)
- Baseline walk distance 100 to 400 meters
Key exclusion criteria (7 listed)
- Use of endothelin receptor antagonist, prostacyclin or PDE-5 inhibitor within 4 weeks of enrollment
- Exercise capacity limited by other illness (other lung disease, arthritis, mobility limitations)
- Uncontrolled systemic hypertension
- Uncontrolled atrial fibrillation
- Severe valvular disease
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 |
|---|---|---|
| AmbrisentanAlso: LetairisSubjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable). | Drug | 1 |
| PlaceboAlso: The placebo will look identical to the Ambrisentan tabletsSugar pill | Other | 2 |
Primary outcome
Change in Pulmonary Vascular Resistance (Wood Units)
Time frame: Baseline and Four months
The primary efficacy outcome will be Pulmonary Vascular Resistance.PVR will be calculated as [(PA mean - wedge) / Cardiac Output]
Safety Assessment-Number of Subjects Who Are Free and Those Who Developed Clinically Significant Adverse Events (CSAEs)
Time frame: 4 months
Freedom from clinically significant adverse events will be measure by determining the number free from CSAEs and those who developed CSAEs
3 secondary outcomes
Change in 6 Minute Walk Distance
Time frame: Baseline and Four months
Change in Functional Class
Time frame: basline and 4 months
Change in Short Form-36 Physical Functioning
Time frame: baseline 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2020.
- 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.
Kelly M Chin, MD principal investigator
University of Texas Southwestern Medical Center
Fernando Torres, MD principal investigator
University of Texas Southwestern Medical Center
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 Ambrisentan in people with Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction, run by University of Texas Southwestern Medical Center 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 10 inclusion and 7 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 19 May 2020. 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 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 22 May 2019). 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 Pulmonary Vascular Resistance (Wood Units) (time frame: Baseline and Four months). The study lists 2 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 19 May 2020.