Abstract:
:This manuscript on endpoints incorporates the broad experience of members of Pulmonary Vascular Research Institute's Innovative Drug Development Initiative as an open debate platform for academia, the pharmaceutical industry and regulatory experts surrounding the future design of clinical trials in pulmonary hypertension. It reviews our current understanding of endpoints used in phase 2 and 3 trials for pulmonary hypertension 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.
journal_name
Pulm Circjournal_title
Pulmonary circulationauthors
Sitbon O,Nikkho S,Benza R,Cq Deng C,W Farber H,Gomberg-Maitland M,Hassoun P,Meier C,Pepke-Zaba J,Prasad K,Seeger W,Corris PAdoi
10.1177/2045894020962960subject
Has Abstractpub_date
2020-11-18 00:00:00pages
2045894020962960issue
4eissn
2045-8932issn
2045-8940pii
10.1177_2045894020962960journal_volume
10pub_type
杂志文章abstract::Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of this study is to present a detailed analysis of cases of PTTM reported in literature in the hopes of achieving more ante-mortem diagnoses. We conducted...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019851000
更新日期:2019-04-01 00:00:00
abstract::The maintenance of endothelial barrier integrity is absolutely essential to prevent the vascular leak associated with pneumonia, pulmonary edema resulting from inhalation of toxins, acute elevation to high altitude, traumatic and septic lung injury, acute lung injury (ALI), and its life-threatening complication, acute...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018773044
更新日期:2018-04-01 00:00:00
abstract::Oral treprostinil (TRE) is a prostacylin that is approved for the treatment of patients with pulmonary arterial hypertension (PAH). Dosing is approved for two or three times daily (t.i.d.); however, adverse effects, including gastrointestinal-related symptoms, may limit the ability to reach optimal doses. We report ou...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045893217744512
更新日期:2018-01-01 00:00:00
abstract::The present study aimed to propose the pulmonary hypertension for predicting left ventricular dysfunction in adults after patent ductus arteriosus closure. A total of 183 patients (age ≥18 years) after patent ductus arteriosus occlusion were retrospectively collected in this study. In brief, pre-, post-procedure and s...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019888428
更新日期:2019-11-15 00:00:00
abstract::Quantifying metabolic derangements in pulmonary hypertension (PH) by plasma metabolomics could identify biomarkers useful for diagnosis and treatment. The objective of this paper is to test the hypotheses that circulating metabolites are differentially expressed in PH patients compared with controls and among differen...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/690554
更新日期:2017-02-01 00:00:00
abstract::Vasculopathies, characterized by the formation of fragile and abnormal microvessels, are associated with the severity of many chronic lung diseases, including pulmonary fibrosis, emphysema/chronic obstructive pulmonary disease, systemic sclerosis, and hypertension. However, the study of human lung vasculature has been...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217702346
更新日期:2017-03-27 00:00:00
abstract::Little is known about the impact of metabolic syndrome (MS) on right ventricular (RV) structure and function. We hypothesized that mice fed a Western diet (WD) would develop RV lipid accumulation and impaired RV function, which would be ameliorated with metformin. Male C57/Bl6 mice were fed a WD or standard rodent die...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018817741
更新日期:2019-01-01 00:00:00
abstract::Our aim is to assess the safety and potential efficacy of a novel treatment paradigm in pulmonary arterial hypertension (PAH), immunomodulation by blocking interleukin-6 (IL6) signaling with the IL6 receptor antagonist, tocilizumab. Inflammation and autoimmunity are established as important in PAH pathophysiology. One...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217735820
更新日期:2018-01-01 00:00:00
abstract::There are limited data on the management of pulmonary arterial hypertension (PAH) in the elderly; therefore, this analysis compared the safety and efficacy of tadalafil between patients ≥65 and <65 years old. This was a post hoc analysis of the randomized, double-blind, placebo-controlled phase 3 Pulmonary Arterial Hy...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674901
更新日期:2014-03-01 00:00:00
abstract::African Americans (AA) have a higher incidence of pulmonary hypertension (PH) risk factors. Few studies have examined the racial differences in the prevalence and etiology of PH and direct comparison of invasive hemodynamics between AAs and Caucasians has rarely been reported. In this study, we examined whether racial...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018764273
更新日期:2018-04-01 00:00:00
abstract::Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory-related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to ch...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688059
更新日期:2016-09-01 00:00:00
abstract::Many dyspneic patients who undergo computerized tomographic pulmonary angiography (CTPA) for presumed acute pulmonary embolism (PE) have no identified cause for their dyspnea yet have persistent symptoms, leading to more CTPA scanning. Right ventricular (RV) dysfunction or overload can signal treatable causes of dyspn...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/679723
更新日期:2015-03-01 00:00:00
abstract::Chronic lung disease (CLD), including pulmonary fibrosis (PF) and chronic obstructive pulmonary disease (COPD), is the fourth leading cause of mortality worldwide. Both are debilitating pathologies that impede overall tissue function. A common co-morbidity in CLD is vasculopathy, characterized by deregulated angiogene...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217739807
更新日期:2018-01-01 00:00:00
abstract::Atrial arrhythmias are common during episodes of acute respiratory failure in patients with chronic lung disease-associated pulmonary hypertension. Expert opinion suggests that management of atrial arrhythmias in patients with pulmonary hypertension should aim to restore sinus rhythm. This is clinically challenging in...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1177/2045894020910685
更新日期:2020-03-09 00:00:00
abstract::Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilo...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/685549
更新日期:2016-06-01 00:00:00
abstract::Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition characterized by single or recurrent pulmonary thromboemboli, which promote pulmonary vascular remodeling. MicroRNA (miRNA), is a small, noncoding RNA that is involved in multiple cell processes and functions and may partici...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674310
更新日期:2013-09-01 00:00:00
abstract::Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geome...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018800439
更新日期:2018-10-01 00:00:00
abstract::Pharmacokinetic studies with oral treprostinil demonstrate that three times daily (TID) dosing reduces peak-to-trough plasma trepostinil fluctuations compared with twice daily (BID) dosing. TID dosing may allow for faster titration, higher total daily doses, and potentially improve the tolerability of oral trepostinil...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018770654
更新日期:2018-04-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a major complication of sickle cell disease (SCD). Low levels of apolipoprotein A1 (Apo-A1) have been implicated in the development of PAH in SCD. We speculate that lower levels of Apo-A1 are related to dysregulation of the ubiquitin-proteasome pathway (UPP). Of 36 recruited pa...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674763
更新日期:2013-12-01 00:00:00
abstract::Patients with pulmonary hypertension are more sedentary than the general population, but attitudes and experiences that may influence their exercise behaviour remain poorly understood. This study identified patterns of behaviour, attitudes towards exercise, barriers and enablers of exercise for people living with pulm...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020968023
更新日期:2020-11-16 00:00:00
abstract::Echocardiography, a non-invasive and cost-effective method for monitoring cardiac function, is commonly used for evaluation and pre-clinical diagnostics of pulmonary hypertension (PH). Previous echocardiographic studies in experimental models of PH are fragmentary in terms of the evaluation of right ventricle (RV) fun...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019841987
更新日期:2019-04-01 00:00:00
abstract::We hypothesized that vibrations created by the pulmonary circulation would create sound like the vocal cords during speech and that subjects with pulmonary artery hypertension (PAH) might have a unique sound signature. We recorded heart sounds at the cardiac apex and the second left intercostal space (2LICS), using a ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/683694
更新日期:2015-12-01 00:00:00
abstract::Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real-world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare cos...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019880086
更新日期:2020-03-18 00:00:00
abstract::Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this "estrogen paradoxȍ of enhanced female survival despite increased female susceptibility remains a mystery, recent pro...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.4103/2045-8932.114756
更新日期:2013-04-01 00:00:00
abstract::Hypereosinophilic syndrome is a myeloproliferative disorder characterized by persistent eosinophilia with involvement of multiple organs. The occurrence of severe pulmonary hypertension (PH) in the setting of hypereosinophilic syndrome is very uncommon. A 43-year-old man with documented idiopathic hypereosinophlic syn...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045894018793999
更新日期:2019-01-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is characterized by obstruction of pre-capillary pulmonary arteries, which leads to sustained elevation of pulmonary arterial pressure. Identifying those at risk through early interventions, such as genetic testing, may mitigate disease course. Current practice guidelines recommen...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217700156
更新日期:2017-04-01 00:00:00
abstract:: ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019865158
更新日期:2019-07-03 00:00:00
abstract::Pulmonary capillary hemangiomatosis (PCH) is a rare form of pulmonary arterial hypertension (PAH) characterized by pulmonary capillary proliferation and pseudoinvasion of collagenous septal structures. PCH is often accompanied by veno-occlusive changes and pulmonary hypertensive arterial remodeling. The clinical and p...
journal_title:Pulmonary circulation
pub_type:
doi:10.1086/682227
更新日期:2015-09-01 00:00:00
abstract::Pulmonary arterial dilatation associated with pulmonary hypertension may result in significant compression of local structures. Left main coronary artery and left recurrent laryngeal nerve compression have been described. Tracheobronchial compression from pulmonary arterial dilatation is rare in adults, and there are ...
journal_title:Pulmonary circulation
pub_type:
doi:10.1086/683687
更新日期:2015-12-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a rapidly progressive and fatal disease for which there is an ever-expanding body of genetic and related pathophysiological information on disease pathogenesis. The most common single culprit gene known is BMPR2, and animal models of the disease in several forms exist. There is...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.87293
更新日期:2011-07-01 00:00:00