Iloprost Improves Gas Exchange in Patients With Pulmonary Hypertension and ARDS

Sawheny, Eva; Ellis, Ashley; Kinasewitz, Gary T.

doi:10.1378/chest.12-2296

Cited by 49 publications

(55 citation statements)

References 27 publications

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“…In a previous study on iloprost with 20 patients, an increase from 177 ± 60 to 213 ± 67 was observed for the PaO 2 /FiO 2 , which was significant at the 0.01 level [27]. Recalculation shows that the intraindividual standard deviation must have been considerably smaller, as a p value of 0.01 corresponds to an effect size of 0.93 (intraindividually) and thus to an intraindividual standard deviation of approximately 40 in this study.…”

Section: Statistical Analyses Study Population Definitionsupporting

confidence: 60%

“…Here, again, iloprost showed an anti-inflammatory effect. In addition, the shunt fraction could be reduced, which resulted in improved oxygenation and improved pulmonary dynamics, which is essential for the reinstitution of spontaneous ventilation during and following ARDS [22,23,[25][26][27]. This shows that the preclinical data identified a beneficial effect of iloprost on ARDS.…”

Section: Iloprostmentioning

confidence: 86%

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Therapeutic iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo trial): a prospective, randomized, multicenter phase II study

Haeberle

Prohaska

Martus

et al. 2020

Trials

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Background: Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. Methods: The Therapeutic Iloprost during ARDS trial (ThIlo trial) is a multicenter, randomized, single blinded, clinical phase II trial assessing the efficacy of inhaled iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index and a health care-related questionnaire, and frailty (Vulnerable Elders Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO 2 /FiO 2 . Secondary endpoints include 90day all-cause mortality, Sequential Organ Failure Assessment scores during the study period up to day 90, the duration of mechanical ventilation, the length of intensive care unit (ICU) stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness, and discharge localization. The study will be conducted in three university ARDS centers in Germany. Discussion: The results of the ThIlo trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in patients with ARDS.

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Section: Statistical Analyses Study Population Definitionsupporting

confidence: 60%

Section: Iloprostmentioning

confidence: 86%

Therapeutic iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo trial): a prospective, randomized, multicenter phase II study

Haeberle

Prohaska

Martus

et al. 2020

Trials

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“…Currently, oxygen supplementation and lung-protective ventilation strategies remain the cornerstones of ARDS treatment, although ultimately both therapies can exacerbate pre-existing lung damage and promote pro-inflammatory cytokine release[6]. Multiple other therapies including nitric oxide[7], surfactant[8], prostaglandins[9], fluid balance[10] and high frequency ventilation[11] have failed to improve survival rates. To ameliorate the exaggerated pulmonary and systemic proinflammatory response occurring in ARDS patients, intravenous glucocorticoid therapy has been studied in the adult population[12].…”

Section: Introductionmentioning

confidence: 99%

Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial

et al. 2016

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Objective A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients. Design Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7. Setting Tertiary care children’s hospital. Patients Children (0–18 years) with ARDS undergoing mechanical ventilation. Interventions 35 children were randomized within 72 hours of mechanical ventilation. The glucocorticoid group received methylprednisolone 2 mg/kg loading dose followed by 1 mg/kg/day continuous infusion from days 1–7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7. Results At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson’s correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity. Conclusion This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.

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“…Moreover, no adverse effect was observed on aneurysmal formation or progression with the clinical use of iloprost (a synthetic prostacyclin analog) in the treatment of pulmonary hypertension. 31,32 These findings support the safety of prostacyclin in the aortic aneurysm pathology; however, its safety should be verified using an atherosclerotic aneurysm animal model, which may prove difficult because of the lack of an available atherosclerotic large animal model.…”

Section: Study Limitationsmentioning

confidence: 72%

Development of a prostacyclin-agonist–eluting aortic stent graft enhancing biological attachment to the aortic wall

Watanabe

Miyagawa

Fukushima

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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Iloprost Improves Gas Exchange in Patients With Pulmonary Hypertension and ARDS

Cited by 49 publications

References 27 publications

Therapeutic iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo trial): a prospective, randomized, multicenter phase II study

Therapeutic iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo trial): a prospective, randomized, multicenter phase II study

Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial

Development of a prostacyclin-agonist–eluting aortic stent graft enhancing biological attachment to the aortic wall

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