Baseline NT-proBNP correlates with change in 6-minute walk distance in patients with pulmonary arterial hypertension in the pivotal inhaled treprostinil study TRIUMPH-1

Frantz, Robert P.; McDevitt, Susanne; Walker, Susan

doi:10.1016/j.healun.2012.04.005

Cited by 19 publications

(15 citation statements)

References 20 publications

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“…42, 43 Recently, it has been demonstrated that baseline NT-proBNP can directly correlate with 6MWD. 44 This provides an additional evaluation to be utilized in clinical trials for PAH. BNP levels are also increased, albeit to lower levels, in patients with primary and severe secondary PH; the degree of elevation reflects the patient's clinical and hemodynamic status.…”

Section: Tests To Evaluate Prognosismentioning

confidence: 99%

Pulmonary Arterial Hypertension

Lai

Potoka

Champion

et al. 2014

Circulation Research

338

257

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Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation.

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Section: Tests To Evaluate Prognosismentioning

confidence: 99%

Pulmonary Arterial Hypertension

Lai

Potoka

Champion

et al. 2014

Circulation Research

338

257

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“…It has been studied to determine whether the baseline NT-pro-BNP levels correlated with improvement in 6MWD, in a randomized, placebo controlled, double-blind study of the inhaled treprostinil to oral therapy for 178 adults with PAH. 31 In this study, the authors found that baseline NT-pro-BNP levels had a strong interaction with treatment response in predicting change from baseline for 6MWD ( P <0.01). Patients with high levels of NT-proBNP at baseline showed greater improvement in 6MWD after treprostinil treatment.…”

Section: Resultsmentioning

confidence: 62%

Reliable and developmentally appropriate study end points are needed to achieve drug development for treatment of pediatric pulmonary arterial hypertension

et al. 2016

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OBJECTIVE To identify suitable end points and surrogates for pediatric pulmonary arterial hypertension (PAH) as the lack of developmentally appropriate end point and clinical trials contribute to the unmet medical need. STUDY DESIGN Reviewed the efficacy end points and surrogates for all trials (1995 to 2013) that were submitted to the Food and Drug Administration (FDA) to support the approval of PAH therapy and conducted literature search. RESULTS An increase in the 6 min walking distance (6MWD) was used as a primary end point in 8/9 adult PAH trials. This end point is not suitable for infants and young children because of performance limitations and lack of control data. One adult PAH trial used time to the first morbidity or mortality event as a primary end point, which could potentially be used in pediatric PAH trials. In the sildenafil pediatric PAH trial, the change in pulmonary vascular resistance index or mean pulmonary artery pressure was used as a surrogate for the 6MWD to assess exercise capacity. However, two deaths and three severe adverse events during the catheterizations made this an unacceptably high-risk surrogate. The INOmax persistent pulmonary hypertension of the newborn trial used a reduction in initiation of extracorporeal membrane oxygenation treatment as a primary end point, which is not feasible for other pediatric PAH trials. A Literature review revealed none of the existing noninvasive markers are fully validated as surrogates to assess PAH efficacy and long-term safety. CONCLUSIONS For pediatric PAH trials, clinical end points are acceptable, and novel validated surrogates would be helpful. FDA seeks collaboration with academia, industry and parents to develop other suitable and possibly more efficient efficacy end points to facilitate pediatric PAH drug development.

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“…However, studies showed that both NT-proBNP at rest and submaximal effort (6MWT) have similar prognostic accuracy for preoperative risk assessment (26,27). Also, it seems that NT-proBNP correlates with the 6MWT in patients with chronic pulmonary thromboembolism treated with treprostinil (28,29).…”

Section: Discussionmentioning

confidence: 99%