Iloprost 20micrograms/1ml nebuliser liquid ampoules

BackgroundPulmonary arterial hypertension (PAH) is a progressive, fatal cardiopulmonary disorder characterized by elevated pulmonary vascular resistance leading to right heart failure. Current treatment utilizes pathway-specific vasodilators, including numerous prostacyclin therapies with diverse delivery methods. Despite available options, head-to-head studies comparing these treatments remain scarce.AimThis network meta-analysis seeks to systematically evaluate all prostacyclin-based PAH therapies to guide clinical decision-making regarding treatment selection.MethodsWe implemented a frequentist approach to network meta-analysis (NWM). For continuous outcomes, we calculated pooled mean differences (MD), whereas risk ratios (RR) were determined for binary endpoints. All estimates incorporated 95% confidence intervals. Results achieving p-values below 0.05 were considered statistically significant.ResultsOur NWM comprising 32 studies (N = 7,819) revealed significant mortality reduction with treprostinil versus placebo (RR 0.66, 95%CI 0.49-0.90), while epoprostenol transitioned demonstrated superior survival benefit (P-score 0.78). For functional capacity, epoprostenol exhibited the greatest 6-Minute Walking Distance (6MWD) improvement (46.84 m, 95%CI 21.90-71.78; P-score 0.90) versus placebo. Hemodynamically, epoprostenol achieved optimal Pulmonary Arterial Pressure (PAP) reduction (-6.29 mmHg, 95%CI -6.99 to -5.59; P-score 0.95), while iloprost demonstrated superior Pulmonary Vascular Resistance (PVR) improvement (-342.09, 95%CI -410.30 to -273.87; P-score 1.00). Epoprostenol ranked highest for Right Atrial Pressure (RAP) reduction (-2.41 mmHg, 95%CI -2.65 to -2.18) and cardiac index improvement (0.56, 95%CI 0.49-0.63). Regarding clinical worsening, selexipag showed potential superiority (RR 0.62, 95%CI 0.51-0.74; P-score 0.95) compared to treprostinil (P-score 0.55).ConclusionOur NMA demonstrates that prostacyclin pathway therapies offer benefits in PAH management. While epoprostenol exhibits superior improvements in hemodynamics and functional capacity, treprostinil reduces mortality by 34%, and selexipag excels in preventing clinical worsening and hospitalizations.

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ImportanceSoluble thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble thrombomodulin (>10 ng/mL) have been associated with worse organ dysfunction and mortality.ObjectiveTo assess the effects of treatment with iloprost vs placebo on the severity of organ failure in patients with septic shock and plasma levels of soluble thrombomodulin higher than 10 ng/mL.Design, setting, and participantsThis investigator-initiated, adaptive, parallel group, stratified, double-blind randomized clinical trial was conducted between November 1, 2019, and July 5, 2022, at 6 hospitals in Denmark. The trial had a maximum sample size of 380, with an interim analysis for futility only at 200 patients with 90 days of follow-up. In total, 279 adults in the intensive care unit (ICU) with septic shock and endotheliopathy were included.InterventionsPatients were randomized 1:1 to masked intravenous infusion of iloprost, 1 ng/kg/min (n = 142), or placebo (n = 137) for 72 hours.Main outcomes and measuresThe primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score in the ICU adjusted for trial site and baseline SOFA score for the per-protocol population. SOFA scores for each of the 5 organ systems ranged from 0 to 4, with higher scores indicating more severe dysfunction (maximum score, 20). The secondary outcomes included serious adverse reactions and serious adverse events at 7 days and mortality at 90 days.ResultsOf 279 randomized patients, data from 278 were analyzed (median [IQR] age, 69 [58-77] years; 171 (62%) male), 142 in the iloprost group and 136 in the placebo group. The trial was stopped for futility at the planned interim analysis. The mean [IQR] daily SOFA score was 10.6 (6.4-14.8) in the iloprost group and 10.5 (5.9-15.5) in the placebo group (adjusted mean difference, 0.2 [95% CI, -0.8 to 1.2]; P = .70). Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group (adjusted relative risk, 1.12 [95% CI, 0.91-1.40]; P = .33). Serious adverse events occurred in 26 of 142 patients (18%) for the iloprost group vs 20 of 136 patients (15%) for the placebo group (adjusted relative risk, 1.25 [95% CI, 0.73-2.15]; P = .52). Only 1 serious adverse reaction was observed.Conclusions and relevanceIn this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng/kg/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients.Trial registrationClinicalTrials.gov Identifier: NCT04123444.

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