Pulmonary Arterial HypertensionPhase 4GOSPELNCT03236818
Goal Oriented Strategy to Preserve Ejection Fraction Trial
A Phase 4 study testing ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan) in people with Pulmonary Arterial Hypertension, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
In this prospective long term feasibility study we examine whether a goal oriented therapeutic strategy that is able to preserve right ventricular function will result in improved clinical outcome in patients with pulmonary arterial hypertension. 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?
- ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2013to Sep 2017
- Phase
- Phase 4
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Idiopathic or heritable pulmonary arterial hypertension
- New York Heart Association (NYHA) functional class II or III
Who cannot join
- Other causes of pulmonary arterial hypertension (i.e. collagen vascular disease, congenital heart disease, chrono-thromboembolic pulmonary hypertension, pulmonary venous hypertension, left heart failure, hypoxemic lung disease)
- Pulmonary arterial hypertension targeted therapies before study inclusion
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center, dept Pulmonary diseases
Amsterdam, 1081 HV
About this study
Official title: Raising the Bars in the Treatment of Pulmonary Arterial Hypertension: Goal Oriented Strategy to Preserve Ejection Fraction Trial
In this prospective long term feasibility study we examine whether a goal oriented therapeutic strategy that is able to preserve right ventricular function will result in improved clinical outcome in patients with pulmonary arterial hypertension. We hypothesize that right ventricular function can only be preserved when early and aggressive medical combination therapy not only reduces pulmonary vascular resistance but also pulmonary pressures.
Read the detailed description
Rationale:
The current strategy in patients with pulmonary arterial hypertension (PAH)is to improve exercise capacity which can be achieved by decreasing pulmonary vascular resistance (PVR) and subsequently increasing cardiac output (CO). Despite this load reduction, a substantial proportion of patients show progressive right ventricular (RV) dysfunction leading to clinical worsening and death. A possible explanation is that current therapies show a relatively modest reduction in PVR, leaving mean pulmonary artery pressure (mPAP) unchanged. As a consequence RV work, defined as the product of CO and mPAP increases, contributing to progressive RV dysfunction.
Hypothesis:
A goal oriented therapeutic strategy that is able to preserve RV function will result in improved clinical outcome. RV function can only be preserved when early and aggressive combination therapy not only reduces PVR but also mPAP.
Study questions:
- Will a goal oriented strategy to preserve/improve RV function, measured by right ventricular ejection fraction (RVEF) be effective?
- Does early and aggressive combination therapy result in improved RV function and survival during long term follow-up?
- Does a strategy to preserve RVEF also translate into improvements of other clinically meaningful parameters?
- Can RVEF be replaced by more simple measures?
- Will a goal oriented strategy to improve RVEF also lead to improvement of myocardial performances and coupling of the RV to its load?
Study design and study population:
In this prospective longitudinal feasibility study, thirty newly diagnosed idiopathic or heritable PAH patients with New York Heart Association (NYHA) functional class II or III will be included. Maintenance/improvement of RVEF will be our primary outcome parameter and therefore cardiac magnetic resonance imaging (CMR) will be performed at baseline and at 4, 8 , 12 and 24 months of follow-up. Six-minute walk testing (6MWT), quality of life questionnaires and blood sampling (NT-proBNP) will be performed at similar follow-up intervals. In addition, right heart catheterization (RHC) will be performed at baseline, after 4, 12 and 24 months of follow-up.
NYHA II patients will start with single agent medical treatment whereas patients with NYHA III will start on combination therapy (2 treatments). In case of a stable/improved RVEF during each follow-up measurement (defined as no decrease in RVEF >3% compared to previous measurement), the treatment strategy will remain unchanged. In case of decreased RVEF >3%, additional medical therapy will be added. Our hypothesis will prove to be correct when the additional medical treatment result in improved RVEF during the subsequent follow-up measurement.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)
- Keywords
- pulmonary arterial hypertension, right ventricle, MRI, medical combination therapy
- 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.
ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)Drug
Combination of an ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)
| Study group | Role | What they receive |
|---|---|---|
| Upfront combination therapy | Other | Combination of an ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan) Receives: Drug: ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in right ventricular ejection fraction
The primary endpoint will be change in right ventricular ejection fraction (RVEF) during 2 years of follow-up.
Measured: 4,12, 24 months of follow-up
Secondary outcomes (5)
pulmonary vascular resistance
Change in pulmonary vascular resistance
Measured: 4,12, 24 months of follow-up
mPAP
Change in mPAP
Measured: 4,12, 24 months of follow-up
Cardiac output in L/min (Thermodilution method)
Change in cardiac output
Measured: 4,8, 12, 24 months of follow-up
Exercise capacity
Change in exercise capacity
Measured: 4,8, 12, 24 months of follow-up
New York Heart Association functional class
Change in New York Heart Association functional class
Measured: 4,8, 12, 24 months of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2017
- Study startMay 2013
- Primary completionSep 2017 (estimated)
- Study completionSep 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, A. Vonk Noordegraaf, Amsterdam UMC, location VUmc
- Investigators
- Anton Vonk Noordegraaf, MD, PhD, Principal investigator, VU University Medical Center, department of pulmonary diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03236818
- Sponsor's protocol ID
- NL41878.029.13
- Acronym
- GOSPEL
- Status last verified
- Jul 2017
- First submitted
- 18 Mar 2013
- Last updated
- 2 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Raising the Bars in the Treatment of Pulmonary Arterial Hypertension: Goal Oriented Strategy to Preserve Ejection Fraction Trial
- ClinicalTrials.gov ID
- NCT03236818
- Acronym / sponsor ID
- GOSPEL / NL41878.029.13
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- pulmonary arterial hypertension, right ventricle, MRI, medical combination therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Sep 2017 (estimated)
- First posted
- 2 Aug 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.
In this prospective long term feasibility study we examine whether a goal oriented therapeutic strategy that is able to preserve right ventricular function will result in improved clinical outcome in patients with pulmonary arterial hypertension. We hypothesize that right ventricular function can only be preserved when early and aggressive medical combination therapy not only reduces pulmonary vascular resistance but also pulmonary pressures.
Detailed description
Rationale:
The current strategy in patients with pulmonary arterial hypertension (PAH)is to improve exercise capacity which can be achieved by decreasing pulmonary vascular resistance (PVR) and subsequently increasing cardiac output (CO). Despite this load reduction, a substantial proportion of patients show progressive right ventricular (RV) dysfunction leading to clinical worsening and death. A possible explanation is that current therapies show a relatively modest reduction in PVR, leaving mean pulmonary artery pressure (mPAP) unchanged. As a consequence RV work, defined as the product of CO and mPAP increases, contributing to progressive RV dysfunction.
Hypothesis:
A goal oriented therapeutic strategy that is able to preserve RV function will result in improved clinical outcome. RV function can only be preserved when early and aggressive combination therapy not only reduces PVR but also mPAP.
Study questions:
- Will a goal oriented strategy to preserve/improve RV function, measured by right ventricular ejection fraction (RVEF) be effective?
- Does early and aggressive combination therapy result in improved RV function and survival during long term follow-up?
- Does a strategy to preserve RVEF also translate into improvements of other clinically meaningful parameters?
- Can RVEF be replaced by more simple measures?
- Will a goal oriented strategy to improve RVEF also lead to improvement of myocardial performances and coupling of the RV to its load?
Study design and study population:
In this prospective longitudinal feasibility study, thirty newly diagnosed idiopathic or heritable PAH patients with New York Heart Association (NYHA) functional class II or III will be included. Maintenance/improvement of RVEF will be our primary outcome parameter and therefore cardiac magnetic resonance imaging (CMR) will be performed at baseline and at 4, 8 , 12 and 24 months of follow-up. Six-minute walk testing (6MWT), quality of life questionnaires and blood sampling (NT-proBNP) will be performed at similar follow-up intervals. In addition, right heart catheterization (RHC) will be performed at baseline, after 4, 12 and 24 months of follow-up.
NYHA II patients will start with single agent medical treatment whereas patients with NYHA III will start on combination therapy (2 treatments). In case of a stable/improved RVEF during each follow-up measurement (defined as no decrease in RVEF >3% compared to previous measurement), the treatment strategy will remain unchanged. In case of decreased RVEF >3%, additional medical therapy will be added. Our hypothesis will prove to be correct when the additional medical treatment result in improved RVEF during the subsequent follow-up measurement.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Upfront combination therapy | Other | Drug: ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)Combination of an ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Idiopathic or heritable pulmonary arterial hypertension
- New York Heart Association (NYHA) functional class II or III
Key exclusion criteria (2 listed)
- Other causes of pulmonary arterial hypertension (i.e. collagen vascular disease, congenital heart disease, chrono-thromboembolic pulmonary hypertension, pulmonary venous hypertension, left heart failure, hypoxemic lung disease)
- Pulmonary arterial hypertension targeted therapies before study inclusion
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 |
|---|---|---|
| ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)Combination of an ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan) | Drug | Upfront combination therapy |
Primary outcome
Change in right ventricular ejection fraction
Time frame: 4,12, 24 months of follow-up
The primary endpoint will be change in right ventricular ejection fraction (RVEF) during 2 years of follow-up.
5 secondary outcomes
pulmonary vascular resistance
Time frame: 4,12, 24 months of follow-up
mPAP
Time frame: 4,12, 24 months of follow-up
Cardiac output in L/min (Thermodilution method)
Time frame: 4,8, 12, 24 months of follow-up
Exercise capacity
Time frame: 4,8, 12, 24 months of follow-up
New York Heart Association functional class
Time frame: 4,8, 12, 24 months of follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
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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.
Anton Vonk Noordegraaf, MD, PhD principal investigator
VU University Medical Center, department of pulmonary diseases
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 ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan) in people with Pulmonary Arterial Hypertension, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 2 Aug 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 Netherlands. 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?
Results are not available in the source record.
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: 4,12, 24 months of follow-up). 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 Aug 2017.