A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis

Nathan, Steven D.; Flaherty, Kevin R.; Glassberg, Marilyn K.; Raghu, Ganesh; Swigris, Jeffrey J.; Alvarez, Roger A.; Ettinger, Neil A.; Loyd, JE; Fernandes, Peter; Gillies, Hunter; Kim, Bo; Shah, Parag S.; Lancaster, Lisa

doi:10.1016/j.chest.2020.02.016

Cited by 78 publications

(87 citation statements)

References 22 publications

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“…Studies of pulmonary vasodilators in chronic lung disease-associated PH have been limited to patients with COPD or idiopathic pulmonary fibrosis, only one of the many subtypes of fibrosing lung diseases. While mostly disappointing, recent studies using inhaled NO [130] and inhaled treprostinil showed promising results in patients with idiopathic pulmonary fibrosis and any form of interstitial lung disease, respectively (https:// clinicaltrials.gov/ct2/show/NCT02630316).…”

Section: The Unmet Need Of Group 2 and Group 3 Phmentioning

confidence: 99%

Management of Pulmonary Arterial Hypertension

Mayeux

Pan

Dechand

et al. 2020

Curr Cardiovasc Risk Rep

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Purpose of Review This review focuses on the therapeutic management and individualized approach to Group 1 pulmonary arterial hypertension (PAH), utilizing Food and Drug Administration-approved PAH-specific therapies and various interventional and surgical options for PAH. Recent Findings The paradigm for the optimal management of PAH has shifted in recent years. Upfront combination therapy with an endothelin receptor antagonist and a phosphodiesterase 5 inhibitor is now widely accepted as standard of care. In addition, there is increasing emphasis on starting prostanoids early in order to delay time to clinical worsening. However, less is known regarding which prostanoid agent to initiate and the optimum time to do so. In order to facilitate shared decision-making, there is an increasing need for decision tools based on guidelines and collective clinical experiences to navigate between pharmacologic and interventional treatments, as well as explore innovative, therapeutic pathways for PAH. Summary The management of PAH has become increasingly complex. With a growing number of PAH-specific therapies, intimate knowledge of the therapeutics and the potential barriers to adherence are integral to providing optimal care for this high-risk patient population. While current PAH-specific therapies largely mediate their effects through pulmonary vasodilation, ongoing research efforts are focused on ways to disrupt the mechanisms leading to pulmonary vascular remodeling. By targeting aberrations identified in the metabolism and proliferative state of pulmonary vascular cells, novel PAH treatment pathways may be just on the horizon.

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Section: The Unmet Need Of Group 2 and Group 3 Phmentioning

confidence: 99%

Management of Pulmonary Arterial Hypertension

Mayeux

Pan

Dechand

et al. 2020

Curr Cardiovasc Risk Rep

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“…14 Using the Actigraph device, treatment with inhaled nitric oxide in PH due to lung fibrosis demonstrated, in the first cohort of a phase 2/3 study, improvement in moderate/vigorous physical activity, as well as in overall activity. 15 However, further validation and standardisation of different methods used are needed for the PAH population; these may be forthcoming in larger scale randomised controlled trials (RCTs), such as the phase 4 TRACE study evaluating the effect of selexipag on daily life physical activity and on patient-reported disease symptoms in PAH. 16 A clinically meaningful difference should be determined and predictivity for long-term outcome demonstrated for future studies in the respective target population.…”

Section: Single Improvement Endpointsmentioning

confidence: 99%

Section: Single Improvement Endpointsmentioning

confidence: 99%

Novel composite clinical endpoints and risk scores used in clinical trials in pulmonary arterial hypertension

et al. 2020

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This manuscript on endpoints incorporates the broad experience of members of Pulmonary Vascular Research Instituteâs (PVRI) Innovative Drug Development Initiative (IDDI) as an open debate platform for academia, the pharmaceutical industry and regulatory experts surrounding the future design of clinical trials in pulmonary hypertension (PH). It reviews our current understanding of endpoints used in phase 2 and 3 trials for PH and discusses in detail the value of newer approaches. These include the roles of composite endpoints and how these can be developed and validated. The newer concept of risk analysis is also discussed, including how such risk scores might be utilised as endpoints in clinical trials.

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“…Finally, a recent phase 2b/3 RCT demonstrated a modest improvement in moderate/vigorous physical activity in patients with fibrotic ILD who are at risk for PH and who were treated with pulsed inhaled NO at 30 μg/kg ideal body weight/h over an 8-week period. 43 Although the clinical implications of this remain unclear, inhaled vasodilators may have particular advantages and may mitigate concerns over worsening ventilation-perfusion matching.…”

Section: Pulmonary Hypertension Associated With Interstitial Lung Diseasesmentioning

confidence: 99%

Management of Pulmonary Hypertension Due to Chronic Lung Disease

Sugarman

Weatherald

2021

Methodist DeBakey Cardiovascular Journal

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Pulmonary hypertension (PH) is a known complication of chronic parenchymal lung diseases, including chronic obstructive lung disease, interstitial lung diseases, and more rare parenchymal lung diseases. Together, these diseases encompass two of the five clinical classifications of PH: group 3 (chronic lung disease [CLD] and/or hypoxia) and group 5 (unclear and/or multifactorial mechanisms). The principal management strategy in PH associated with CLD is optimization of the underlying lung disease. There has been increasing interest in therapies that treat pulmonary arterial hypertension (group 1, PAH), and although some studies have explored the use of these oral PAH-targeted therapies to treat PH associated with CLD , there is currently no evidence to support their routine use; in fact, some studies suggest harm. Inhaled therapies that target the pulmonary vasculature may avoid certain problems observed with oral PAH therapies. Recent studies suggest a promising role for inhaled PAH therapies in group 3 PH, but this requires further study. The objective of this article is to review the current treatment strategies for group 3 and group 5 PH.

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A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis

Cited by 78 publications

References 22 publications

Management of Pulmonary Arterial Hypertension

Management of Pulmonary Arterial Hypertension

Novel composite clinical endpoints and risk scores used in clinical trials in pulmonary arterial hypertension

Management of Pulmonary Hypertension Due to Chronic Lung Disease

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