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- Galiè, Nazzareno, et al.
(author)
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Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension
- 2015
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 373:9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.METHODS: In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.RESULTS: The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.CONCLUSIONS: Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).
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| 2. |
- Máñez Costa, Maria, et al.
(author)
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Co-production of Climate Services : A diversity of approaches and good practice from the ERA4CS projects (2017–2021)
- 2022
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Reports (other academic/artistic)abstract
- This guide presents a joint effort of projects funded under the European Research Area for Climate Services (ERA4CS) (http://www.jpi-climate.eu/ERA4CS), a co- funded action initiated by JPI Climate with co-funding by the European Union (Grant 690462), 15 national public Research Funding Organisations (RFOs), and 30 Research Performing Organisations (RPOs) from 18 European countries. This guide sets out to increase the understanding of different pathways, methods, and approaches to improve knowledge co-production of climate services with users as a value-added activity of the ERA4CS Programme.Reflecting on the experiences of 16 of the 26 projects funded under ERA4CS, this guide aims to define and recommend good practices for transdisciplinary knowledge co-production of climate services to researchers, users, funding agencies, and private sector service providers. Drawing on responses from ERA4CS project teams to a questionnaire and interviews, this guide maps the diversity of methods for stakeholder identification, involvement, and engagement. It also conducts an analysis of methods, tools, and mechanisms for engagement as well as evaluation of co-production processes.This guide presents and discusses good practice examples based on the review of the ERA4CS projects, identifying enablers and barriers for key elements in climate service co-production processes. These were: namely (i) Forms of Engagement; (ii) Entry Points for Engagement; and, (iii) Intensity of Involvement. It further outlines key ingredients to enhance the quality of co-producing climate services with users and stakeholders.Based on the analysis of the lessons learned from ERA4CS projects, as well as a review of key concepts in the recent literature on climate service co-production, we provide a set of recommendations for researchers, users, funders and private sector providers of climate services.
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