Safety and Tolerability of Continuous Inhaled Iloprost Therapy for Severe Pulmonary Hypertension in Neonates and Infants
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SUBMITTER: Krishnan A
PROVIDER: S-EPMC11201391 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:BackgroundInhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy.AimsIn this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6-9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed.ResultsMost patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (-74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001).ConclusionsPulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status.
| S-EPMC3561685 | biostudies-literature
Project description:The INSPIRE trial was a Phase 3, open-label, multicenter trial (LTI-301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry-powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial. Transition patients initiated Yutrepia at a dose comparable to their nebulized treprostinil dose while prostacyclin naïve patients received 26.5-mcg QID; up-titration in 26.5-mcg increments was permitted for both groups. A total of 121 patients were enrolled, of which 29 patients discontinued from the trial, with the most common reason being AEs. Eighty percent of the Transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg QID at Day 360, respectively, with one patient achieving a dose of 212-mcg QID. The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment-related though mild to moderate in severity and expected for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1 year of treatment. Yutrepia was found to be a convenient, safe, and well-tolerated inhaled prostacyclin treatment option for PAH patients.
| S-EPMC9400582 | biostudies-literature
Project description:Inhaled iloprost is an effective therapy for patients with pulmonary arterial hypertension (PAH); however, some patients experience extended inhalation times when using the V10 formulation (10.0 µg/mL) to deliver a 5 -µg dose (at mouthpiece) and are at risk of incomplete inhalations and reduced inhalation frequency. VENTASWITCH was an observational, case-crossover study to evaluate inhalation behavior in patients with PAH switched from iloprost V10 to V20 (20.0 µg/mL) formulation for delivering a 5 -µg dose using the I-Neb® AAD® device. Adults with PAH participating in a German Ventavis® (iloprost) patient-support program, who were switched from the V10 to V20 formulation, were enrolled. The co-primary endpoints were mean daily proportion of complete inhalations and mean daily inhalation frequency. The secondary endpoint was mean daily inhalation duration. Data were collected for three months before and after switching. Overall, 63 patients were included. Switching from V10 to V20 resulted in a significant increase in the mean daily proportion of complete inhalations (92% vs. 97%, P < 0.0001) and inhalation frequency (4.6 vs. 4.9 inhalations/day, P = 0.0430), and reduction in mean inhalation duration (11.8 vs. 6.5 min; P < 0.0001). Greater increases in daily proportions of complete inhalations were observed in older patients (≥ 65 vs. < 65 years) and those receiving more (3 vs. < 3) concomitant PAH medications. Switching from V10 to V20 iloprost formulation significantly improved inhalation behavior in patients with PAH and may facilitate improved adherence to therapy.
| S-EPMC6128078 | biostudies-literature
Project description:Persistent pulmonary hypertension of the newborn (PPHN) is one of the diseases of the neonate with severe potential morbidity and mortality. Inhaled iloprost, a stable prostacyclin analog, has been suggested as an alternative treatment for inhaled nitric oxide (iNO). However, more data on neonates' dosing, setting, and effectiveness still needs to be solved. This study suggests using inhaled iloprost as rescue therapy for PPHN based on our experience. This was a retrospective study. The data from medical records of six newborns diagnosed with PPHN and had received inhaled iloprost from December 2019 to April 2022 were collected. Demographic and clinical features, dosing regimen, changes in oxygenation index, echocardiographic findings, and mortality were evaluated. The inhalation dose was 2-4 mcg/dose, and 3-48 inhalations per day were applied over 2-7 days. Inhaled iloprost was effective in all patients. No side effects were attributable to inhaled iloprost, and no mortality was recorded. Our experience suggests that inhaled iloprost can be used as a first-line therapy in newborn infants with PPHN when iNO is unavailable. However, there are large fluctuations in the oxygenation index due to the setting.
| S-EPMC10352650 | biostudies-literature
Project description:Doppler echocardiography is useful in the initial evaluation and long-term follow-up of patients with pulmonary artery hypertension. Aerosolised iloprost has been shown to reduce pulmonary pressure immediately after inhalation. We report the echocardiographic findings in a patient with severe pulmonary hypertension, before and after the inhalation of aerosolized iloprost. These findings illustrate the acute influence of iloprost in right and left ventricular hemodynamics and morphology. These findings were reproduced in subsequent echocardiographic evaluations.
| S-EPMC2203975 | biostudies-literature
Project description:AimsAssessing reversibility of pulmonary vascular changes through vasoreactivity testing (VRT) optimizes end-stage heart failure patient selection for heart transplant. All efforts should be made to unload the left ventricle and reduce pulmonary vascular resistance to effectively exclude irreversible pulmonary hypertension.Methods and resultsWe reviewed our centre's cardiac transplant registry database (2009-2017) for VRT and compared haemodynamic responses with 40 ppm inhaled NO (n = 14), 14-17 μg inhaled iloprost (n = 7), and 24 h 0.1 μg/kg/min intravenous levosimendan (n = 14). Response to levosimendan was assessed by repeat right heart catheterization within 72 h. Baseline clinical and haemodynamic features were similar between groups. VRT was well tolerated in all patients. All drugs effectively reduced pulmonary artery pressures and transpulmonary gradient while increasing cardiac index, although levosimendan had a greater impact on cardiac index increase (P = 0.036). Levosimendan was the only drug that reduced pulmonary artery wedge pressure (P = 0.004) and central venous pressures (P < 0.001) and increased both left and right ventricular stroke work indexes (P = 0.020 and P = 0.042, respectively) and cardiac power index (P < 0.001) compared with NO and iloprost. Right ventricular end-diastolic pressures and central venous pressure were only decreased by levosimendan. The rate of positive responses (≥10 mmHg decrease or final mean pulmonary artery pressure ≤40 mmHg with increased/unaltered cardiac index) was lower with inhaled iloprost (14%) than with either levosimendan or NO (71% and 64%, respectively; P < 0.05).ConclusionsLevosimendan may be a safe and effective alternative for pulmonary hypertension reversibility assessment or a valuable pre-test medical optimization tool in end-stage heart failure patient assessment for heart transplantation offering extended haemodynamic benefits. Whether it increases the rate of positive responses or allows a better selection of candidates to heart transplantation remains to be established.
| S-EPMC8006659 | biostudies-literature
Project description:Iloprost, an inhaled synthetic prostacyclin analogue, improves hemodynamic and clinical status with minimal systemic adversity in patients with pulmonary arterial hypertension. Our single-site, prospective case series aimed to determine the effects of iloprost in subjects with group 2 pulmonary hypertension and heart failure with preserved ejection fraction. Patients referred to Boston Medical Center for initial evaluation of suspected pulmonary hypertension received a test dose of 2.5 μg inhaled iloprost, followed by two subsequent doses of 5 μg. Hemodynamic measurements were recorded for each inhalation after 15, 30, 60, and 90 minutes. Results were analyzed via paired t test and signed-rank test. Eight subjects fulfilled criteria and elected to enter the study. There was a reduction of pulmonary arterial pressure (by an average of 7.0 mmHg [P = 0.005] and 4.7 mmHg [P = 0.021] with the first and second 5-μg inhalations, respectively) and pulmonary vascular resistance (by an average of 161.9 dyn·s/cm(5) [P = 0.019] and 95.0 dyn·s/cm(5) [P = 0.014] with the first and second 5-μg inhalations, respectively). There were trends for increased cardiac output and decreased oxygen saturation. There were no changes in other vital or hemodynamic parameters, including pulmonary capillary wedge pressure. All patients completed each cycle of iloprost administration without preestablished termination criteria. In patients with pulmonary hypertension and heart failure with preserved ejection fraction, inhaled iloprost resulted in acute reduction of pulmonary arterial pressure and pulmonary vascular resistance. Further evaluation of iloprost in this subset of patients is warranted.
| S-EPMC4405721 | biostudies-other
Project description:Inhaled iloprost is an established treatment for pulmonary arterial hypertension (PAH). However, the long-term hemodynamic changes that inhaled iloprost induces are unclear. Here, we retrospectively enrolled 18 patients with PAH who received inhaled iloprost as add-on to oral combination therapy from December 2016 to January 2021 at our institute in Japan. We then examined the changes in hemodynamic parameters induced by iloprost in these patients during right heart catheterization (RHC). To examine the long-term effects of iloprost, we repeated the RHC examination at follow-up (median time to follow-up, 8.5 months). During both catheterization procedures, iloprost was administered by using an I-neb AAD system (Philips NV). In a comparison of pre-inhalation values at the first and follow-up RHCs, inhaled iloprost significantly improved mean pulmonary artery pressure (mPAP; 39.9 ± 7.8 to 32.5 ± 7.2 mmHg, p = 0.016) and pulmonary vascular resistance (PVR; 588.5 ± 191.7 to 464.4 ± 188.5 dyn s cm-5, p = 0.047). During the follow-up RHC, in a comparison of the pre-inhalation and best recorded values out to 30 min after the end of iloprost inhalation, iloprost significantly decreased mPAP (32.5 ± 7.2 to 30.0 ± 6.6 mmHg, p = 0.007) and PVR (457.8 ± 181.4 to 386.2 ± 142.8 dyn s cm-5, p = 0.025) and significantly increased cardiac output (4.19 ± 0.91 to 4.64 ± 1.01 L/min, p = 0.035). Iloprost may have not only acute vasodilation effects but also long-term hemodynamic benefits in PAH patients receiving combination therapy.
| S-EPMC9063964 | biostudies-literature
Project description:ImportanceClinical observations of immediate improvement in fraction of inspired oxygen (FiO2) in a proportion of cases is often cited as the rationale for using inhaled nitric oxide (iNO) in the management of acute pulmonary hypertension among very preterm neonates (gestational age, <32 weeks). However, the clinical effectiveness of such a response pattern remains underinvestigated.ObjectiveTo identify factors associated with predischarge mortality among very preterm neonates receiving iNO for acute pulmonary hypertension, with specific a priori emphasis on iNO responsiveness.Design, setting, and participantsThis prospective observational cohort study was conducted from January 1, 2018, to December 31, 2022, at 12 Canadian tertiary neonatal intensive care units. Consecutive very preterm neonates who received iNO for a diagnosis of acute pulmonary hypertension and pretreatment FiO2 of 0.50 or more were included. Neonates with congenital anomalies or those who were treated for chronic pulmonary hypertension with iNO were excluded. Early acute pulmonary hypertension (≤72 hours of age) and late acute pulmonary hypertension (>72 hours of age) cohorts were analyzed separately. Statistical analysis was performed from January 2023 to January 2024.ExposureTreatment with iNO for acute pulmonary hypertension.Main outcomes and measuresThe study cohorts were divided for comparison based on the primary outcome of predischarge mortality. Logistic regression analyses were used with predefined variables, including iNO responsiveness, to identify factors associated with mortality. A positive response to iNO was defined as a pre-iNO minus 4-hour post-iNO FiO2 of 0.20 or more.ResultsThe early acute pulmonary hypertension group (mean [SD] birth gestational age, 26.3 [2.4] weeks; median treatment age, 1 day [IQR, 1-2 days]; 147 boys [56%]) included 262 neonates; 179 (68%) had a pre-iNO FiO2 of 1.0. The late acute pulmonary hypertension group (mean [SD] birth gestational age, 24.9 [1.7] weeks; median treatment age, 13 days [IQR, 9-20 days]; 72 boys [66%]) included 109 neonates; 51 (47%) had a pre-iNO FiO2 of 1.0. Neonates with early acute pulmonary hypertension more frequently had a positive iNO response (71% [186 of 262] vs 41% [45 of 109]) and lower mortality (34% [90 of 262] vs 49% [53 of 109]) than those with late acute pulmonary hypertension. Accounting for pretreatment illness factors, greater reduction in FiO2 with iNO remained associated with lower mortality for neonates with early acute pulmonary hypertension (adjusted odds ratio per FiO2 reduction of 0.10, 0.74 [95% CI, 0.65-0.84]). For those with late acute pulmonary hypertension, however, only pretreatment illness severity (lower pre-iNO FiO2 and higher pre-iNO pH), and not positive response to iNO (adjusted odds ratio, 0.47 [95% CI, 0.17-1.30]), was associated with mortality.Conclusions and relevanceIn this cohort study of very preterm neonates with acute pulmonary hypertension treated with iNO, responsiveness to iNO was associated with improved outcomes during the first 72 hours of age. The prognostic role of iNO response in acute pulmonary hypertension presenting after 72 hours of age remains unclear. Future studies should investigate the distinct pathophysiological mechanisms associated with late acute pulmonary hypertension in this population.
| S-EPMC11811801 | biostudies-literature
Project description: Not available
| S-EPMC8918720 | biostudies-literature