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Goal Oriented Strategy to Preserve Ejection Fraction Trial (GOSPEL)

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ClinicalTrials.gov Identifier: NCT03236818
Recruitment Status : Unknown
Verified July 2017 by A. Vonk Noordegraaf, VU University Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : August 2, 2017
Last Update Posted : August 2, 2017
Sponsor:
Information provided by (Responsible Party):
A. Vonk Noordegraaf, VU University Medical Center

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan) Phase 4

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:

  1. Will a goal oriented strategy to preserve/improve RV function, measured by right ventricular ejection fraction (RVEF) be effective?
  2. Does early and aggressive combination therapy result in improved RV function and survival during long term follow-up?
  3. Does a strategy to preserve RVEF also translate into improvements of other clinically meaningful parameters?
  4. Can RVEF be replaced by more simple measures?
  5. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Raising the Bars in the Treatment of Pulmonary Arterial Hypertension: Goal Oriented Strategy to Preserve Ejection Fraction Trial
Study Start Date : May 2013
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : September 2017


Arm Intervention/treatment
Upfront combination therapy
Combination of an ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)
Drug: ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)
Combination of an ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. pulmonary vascular resistance [ Time Frame: 4,12, 24 months of follow-up ]
    Change in pulmonary vascular resistance

  2. mPAP [ Time Frame: 4,12, 24 months of follow-up ]
    Change in mPAP

  3. Cardiac output in L/min (Thermodilution method) [ Time Frame: 4,8, 12, 24 months of follow-up ]
    Change in cardiac output

  4. Exercise capacity [ Time Frame: 4,8, 12, 24 months of follow-up ]
    Change in exercise capacity

  5. New York Heart Association functional class [ Time Frame: 4,8, 12, 24 months of follow-up ]
    Change in New York Heart Association functional class


Other Outcome Measures:
  1. NT-proBNP [ Time Frame: 4,8, 12, 24 months of follow-up ]
    Change in NT-proBNP

  2. Quality of Life by SF-36 questionnaire [ Time Frame: 4,8, 12, 24 months of follow-up ]
    Change in Quality of Life



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Idiopathic or heritable pulmonary arterial hypertension
  • New York Heart Association (NYHA) functional class II or III

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03236818


Locations
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Netherlands
VU University Medical Center, dept Pulmonary diseases
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
Investigators
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Principal Investigator: Anton Vonk Noordegraaf, MD, PhD VU University Medical Center, department of pulmonary diseases

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Responsible Party: A. Vonk Noordegraaf, Clinical Professor, Principal Investigator, VU University Medical Center
ClinicalTrials.gov Identifier: NCT03236818    
Other Study ID Numbers: NL41878.029.13
First Posted: August 2, 2017    Key Record Dates
Last Update Posted: August 2, 2017
Last Verified: July 2017
Keywords provided by A. Vonk Noordegraaf, VU University Medical Center:
pulmonary arterial hypertension
right ventricle
MRI
medical combination therapy
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Bosentan
Sildenafil Citrate
Tadalafil
Macitentan
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Antihypertensive Agents
Endothelin Receptor Antagonists
Endothelin A Receptor Antagonists
Endothelin B Receptor Antagonists