Goal Oriented Strategy to Preserve Ejection Fraction Trial

Pulmonary Arterial Hypertension Clinical Trial

— GOSPEL  

Official title:

Raising the Bars in the Treatment of Pulmonary Arterial Hypertension: Goal Oriented Strategy to Preserve Ejection Fraction Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03236818
• Other study ID #: NL41878.029.13
• Status: Active, not recruiting
• Phase: Phase 4
• First received: March 18, 2013
• Last updated: August 1, 2017
• Start date: May 2013
• Est. completion date: September 2017

Study information

• Verified date: July 2017
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)
Combination of an ERA and PDE-5I (Sildenafil, Tadalafil, Bosentan, Macitentan)

Locations

Country	Name	City	State
Netherlands	VU University Medical Center, dept Pulmonary diseases	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	NT-proBNP	Change in NT-proBNP	4,8, 12, 24 months of follow-up
Other	Quality of Life by SF-36 questionnaire	Change in Quality of Life	4,8, 12, 24 months of follow-up
Primary	Change in right ventricular ejection fraction	The primary endpoint will be change in right ventricular ejection fraction (RVEF) during 2 years of follow-up.	4,12, 24 months of follow-up
Secondary	pulmonary vascular resistance	Change in pulmonary vascular resistance	4,12, 24 months of follow-up
Secondary	mPAP	Change in mPAP	4,12, 24 months of follow-up
Secondary	Cardiac output in L/min (Thermodilution method)	Change in cardiac output	4,8, 12, 24 months of follow-up
Secondary	Exercise capacity	Change in exercise capacity	4,8, 12, 24 months of follow-up
Secondary	New York Heart Association functional class	Change in New York Heart Association functional class	4,8, 12, 24 months of follow-up