A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen

King, Christopher S.; Flaherty, Kevin R.; Glassberg, Marilyn K.; Lancaster, Lisa; Raghu, Ganesh; Swigris, Jeffrey J.; Argula, Rahul; Dudenhofer, Rosemarie A; Ettinger, Neil A.; Feldman, Jeremy; Johri, Shilpa; Fernandes, Peter; Parsley, Ed; Shah, Parag S.; Nathan, Steven D.

doi:10.1513/annalsats.202107-864oc

Cited by 25 publications

(40 citation statements)

References 28 publications

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“…The use of inhaled pulmonary vasodilator treatment in ILD‐PH 81 , 82 , 83 highlights the relevance of V A /Q relationships. 84 It is known from classical studies in IPF that V A /Q mismatching accounts for 80% of hypoxemia.…”

Section: Phenotypes Of Ph In Ildmentioning

confidence: 99%

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Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative ‐ Group 3 Pulmonary Hypertension

et al. 2023

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Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes.

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Section: Phenotypes Of Ph In Ildmentioning

confidence: 99%

“…These issues also have important implications for clinical trial design, since the most recent definition of ILD‐PH was not employed in the few clinical trials to date. 81 , 82 , 83 …”

Section: Phenotypes Of Ph In Ildmentioning

confidence: 99%

Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative ‐ Group 3 Pulmonary Hypertension

et al. 2023

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“… 8 There have been two independent cohorts studied thus far, both suggesting benefit as evaluated through the novel primary endpoint of actigraphy. 8 , 9 This population was enriched for underlying pulmonary hypertension through the need for supplemental oxygen. Since RHC was not required, there is no further insight as to how many of these patients may have had PH.…”

Section: Prior Clinical Trials In Ph‐ild and Ild With A Vascular Phen...mentioning

confidence: 99%

“…The use of ambulatory inhaled nitric oxide has also been studied in patients with ILD on supplemental oxygen 8 . There have been two independent cohorts studied thus far, both suggesting benefit as evaluated through the novel primary endpoint of actigraphy 8,9 . This population was enriched for underlying pulmonary hypertension through the need for supplemental oxygen.…”

Section: Prior Clinical Trials In Ph‐ild and Ild With A Vascular Phen...mentioning

confidence: 99%

Pulmonary hypertension in interstitial lung disease: Clinical trial design and endpoints: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative—Group 3 Pulmonary Hypertension

et al. 2022

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Pulmonary hypertension (PH) associated with interstitial lung disease (ILD) is an attractive target for clinical trials of PH medications. There are many factors that need to be considered to prime such studies for success. The patient phenotype most likely to respond to the intervention requires weighing the extent of the parenchymal lung disease against the severity of the hemodynamic impairment. The inclusion criteria should not be too restrictive, thus enabling recruitment. The trial should be of sufficient duration to meet the chosen endpoint which should reflect how the patient feels, functions, or survives. This paper summarizes prior studies in PH‐ILD and provides a framework of the type of studies to be considered. Inclusion criteria, clinical trial endpoints, and pharmacovigilance in the context of PH‐ILD trials are also addressed. Through lessons learnt from prior studies, suggestions and guidance for future clinical trials in PH‐ILD are also provided.

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“…In this issue of AnnalsATS , King and colleagues (pp. 594–602 ) report the results of a phase 2 randomized, double-blinded, placebo-controlled trial of 4-month pulsed iNO at 45 μg/kg ideal body weight/hour (iNO45) delivered via the INOpulse (a cylinder-based delivery system) in 44 patients with fibrotic interstitial lung disease (ILD) on home oxygen therapy ( 6 ). Their previous proof-of-concept study found that the use of pulsed iNO at 30 μg/kg ideal body weight/hour (iNO30) for 2 months was safe and improved moderate to vigorous physical activity levels ( 7 ).…”

mentioning

confidence: 99%

Inhaled Nitric Oxide for Fibrotic Interstitial Lung Disease: A Step Forward

Khor

Adegunsoye

2022

Annals ATS

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A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen

Cited by 25 publications

References 28 publications

Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative ‐ Group 3 Pulmonary Hypertension

Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative ‐ Group 3 Pulmonary Hypertension

Pulmonary hypertension in interstitial lung disease: Clinical trial design and endpoints: A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative—Group 3 Pulmonary Hypertension

Inhaled Nitric Oxide for Fibrotic Interstitial Lung Disease: A Step Forward

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