Updating Clinical Endpoint Definitions

Hassoun, Paul M.; Nikkho, Sylvia; Rosenzweig, Erika B.; Moreschi, Gail; Lawrence, John; Teeter, John G.; Meier, Christian; Ghofrani, Hossein Ardeschir; Minai, Omar A.; Rinaldi, Paula; Michelakis, Evangelos D.; Oudiz, Ronald J.

doi:10.4103/2045-8932.109920

Cited by 22 publications

(35 citation statements)

References 112 publications

(156 reference statements)

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“…4,5 While 6MWD has been accepted by regulatory authorities as an end-point for evaluating treatment effects in PAH, the test is not without its limitations. 6,7 Specifically, 6MWT lacks sensitivity and specificity in the diagnosis of PAH, has a significant plateau effect, is not used in an age-adjusted fashion and provides no physiological details in the determinants of exercise limitation. 5,7,8 There is also evidence that a change in 6MWD is a poor surrogate end-point for clinical events.…”

Section: Summary At a Glancementioning

confidence: 99%

“…6,7 Specifically, 6MWT lacks sensitivity and specificity in the diagnosis of PAH, has a significant plateau effect, is not used in an age-adjusted fashion and provides no physiological details in the determinants of exercise limitation. 5,7,8 There is also evidence that a change in 6MWD is a poor surrogate end-point for clinical events. 9 As a result, recent studies evaluating treatment effects in PAH have moved away from using 6MWD as a primary end-point.…”

Section: Summary At a Glancementioning

confidence: 99%

“…9 As a result, recent studies evaluating treatment effects in PAH have moved away from using 6MWD as a primary end-point. 7 Current guidelines also recommend cardiopulmonary exercise testing (CPET) in evaluating exercise capacity in PAH, with peak oxygen consumption ( _ VO 2peak ) being a recognized prognostic indicator for the disease. 7,10 Unlike the 6MWT, CPET provides additional information on physiological limitations in PAH, particularly when other differential diagnoses are being considered.…”

Section: Summary At a Glancementioning

confidence: 99%

“…This is because 6MWT is non‐invasive, well‐defined with standardized guidelines, simple to undertake and the primary outcome, the 6‐min walk distance (6MWD), has been shown to predict morbidity and mortality in PAH . While 6MWD has been accepted by regulatory authorities as an end‐point for evaluating treatment effects in PAH, the test is not without its limitations . Specifically, 6MWT lacks sensitivity and specificity in the diagnosis of PAH, has a significant plateau effect, is not used in an age‐adjusted fashion and provides no physiological details in the determinants of exercise limitation .…”

Section: Introductionmentioning

confidence: 99%

“…There is also evidence that a change in 6MWD is a poor surrogate end‐point for clinical events . As a result, recent studies evaluating treatment effects in PAH have moved away from using 6MWD as a primary end‐point …”

Section: Introductionmentioning

confidence: 99%

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Gas exchange responses during 6‐min walk test in patients with pulmonary arterial hypertension

et al. 2016

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Background and objective: The 6-min walk test (6MWT) is the most widely utilized method of assessing exercise capacity in pulmonary arterial hypertension (PAH). Cardiopulmonary exercise testing has the advantage of providing additional physiological information over 6MWT. The goals of our study were to describe the addition of gas exchange measurements to 6MWT and to determine how these parameters were related to the severity of PAH in three major subgroups of PAH (idiopathic (IPAH), connective tissue diseaserelated (CTPAH) and congenital heart disease-related (CHPAH)). Methods: Seventy-six PAH patients (IPAH, n = 28; CTPAH, n = 24; CHPAH, n = 24) completed the 6MWT with simultaneous gas exchange measurements. The 6-min walk distance (6MWD), oxygen uptake ( _ VO 2 ), carbon dioxide production ( _ VCO 2 ), oxygen saturation, minute ventilation to carbon dioxide output ( _ V E / _ VCO 2 ) and end-tidal partial pressure for carbon dioxide (P ET CO 2 ) were compared between subgroups, different functional classes (FCs) and pharmacotherapy. Results: Whilst no significant difference in 6MWT was observed, absolute _ VO 2 and _ VCO 2 were higher for IPAH (P < 0.05). Differences were removed when _ VO 2 and _ VCO 2 were expressed relative to body mass (i.e. mL/kg/ min). CHPAH had the most significant desaturation during 6MWT (CPAH: 73 AE 15%; CTPAH: 90 AE 8%, IPAH: 92 AE 8%, P < 0.01). There was no difference in _ V E / _ VCO 2 and P ET CO 2 between groups; however, New York Health Association (NYHA) FC II performed better than FC III subjects in 6MWT with lower _ V E / _ VCO 2 and higher end-exercise P ET CO 2 . Similarly, individuals on more advanced pharmacotherapy (triple therapy vs monotherapy) had poorer gas exchange during exercise. Conclusion: Whilst 6MWT and gas exchange did not differentiate between PAH groups, individuals with more

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Section: Summary At a Glancementioning

confidence: 99%

Section: Summary At a Glancementioning

confidence: 99%

Section: Summary At a Glancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Gas exchange responses during 6‐min walk test in patients with pulmonary arterial hypertension

et al. 2016

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Pulmonary Vascular Disease

Rhodes

Opotowsky

2019

Exercise Physiology for the Pediatric and Congenital Cardiologist

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An Update on Medical Therapy for Pulmonary Arterial Hypertension

O’Callaghan

Humbert

2013

Curr Hypertens Rep

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Over the past 20 years, great progress has been made in the treatment of pulmonary arterial hypertension (PAH). Available therapies target one of three principal pathways: the endothelin (ET), nitric oxide (NO) or the prostacyclin (PGI2) pathway. Evidence shows that current drugs, used either as monotherapy or in different combinations, can improve exercise capacity, clinical symptoms, hemodynamics and even survival in PAH. Unfortunately, the disease remains incurable and the prognosis of the disease is still poor. However, existing and novel potent antiproliferative therapies are being explored, and new agents targeting different and/or additional pathways are likely to become available to clinicians in the near future. Promising candidates include tyrosine kinase antagonists (e.g. imatinib); soluble guanylate cyclase stimulators (riociguat); an oral analog of prostacyclin (selexipag); and a tissue targeting endothelin receptor antagonist (macitentan). Phase II or III trials have either been completed or are underway to evaluate the safety and efficacy of these various therapies.

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Updating Clinical Endpoint Definitions

Cited by 22 publications

References 112 publications

Gas exchange responses during 6‐min walk test in patients with pulmonary arterial hypertension

Gas exchange responses during 6‐min walk test in patients with pulmonary arterial hypertension

Pulmonary Vascular Disease

An Update on Medical Therapy for Pulmonary Arterial Hypertension

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