Dataset Information

Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

ABSTRACT: Currently, there are no approved treatments for infants with acute bronchiolitis, the leading cause for hospitalization of infants worldwide, and thus the recommended approach is supportive. Inhaled Nitric oxide (iNO), possesses anti-viral properties, improves oxygenation, and was shown to be safe in infants with respiratory conditions. Hospitalized infants with acute bronchiolitis were therefore recruited to a prospective double-blinded, multi-center, randomized controlled pilot study. They received intermittent high dose iNO (160 ppm) plus oxygen/air for 30?min or oxygen/air alone (control), five times/day, up to 5 days. Sixty-nine infants were enrolled. No difference was observed in frequencies of subjects with at least one Adverse Event (AE) in iNO (44.1%) vs. control (55.9%); neither was Methemoglobin >7% safety threshold. No drug-related serious AEs (SAEs) were reported. Analysis of Per-Protocol population revealed that length of stay (LOS), time to SpO2 ?92%, and time to mTal clinical score ?5 improved by 26.7?±?12.7 (Welch's t-test p?=?0.04), 20.8?±?8.9 (p?=?0.023), and 14.6?±?9.1 (p?=?0.118) hours, respectively, in the iNO group compared to the control. Overall, high dose iNO (160ppm) was safe, well-tolerated, reduced LOS and showed rapid improvement of oxygen saturation, compared to the standard therapy. Further investigation in larger cohorts is warranted to validate these encouraging efficacy outcomes. (Trial registration: NCT03053388).

SUBMITTER: Goldbart A

PROVIDER: S-EPMC7295966 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

Goldbart Aviv A Golan-Tripto Inbal I Pillar Giora G Livnat-Levanon Galit G Efrati Ori O Spiegel Ronen R Lubetzky Ronit R Lavie Moran M Carmon Lior L Ghaffari Abdi A Nahum Amit A

Scientific reports 20200615 1

Currently, there are no approved treatments for infants with acute bronchiolitis, the leading cause for hospitalization of infants worldwide, and thus the recommended approach is supportive. Inhaled Nitric oxide (iNO), possesses anti-viral properties, improves oxygenation, and was shown to be safe in infants with respiratory conditions. Hospitalized infants with acute bronchiolitis were therefore recruited to a prospective double-blinded, multi-center, randomized controlled pilot study. They rec ...[more]

PMID: 32541773

Similar Datasets

Project description:BackgroundAcute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS.MethodsWe performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events.ResultsOf 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO2/FiO2 ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups.ConclusionsThe primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS.Trial registrationThe study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.

Project description:Importance:Bronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks' gestation and is associated with adverse pulmonary and neurodevelopmental outcomes. Objective:To test whether administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 improves the rate of survival without BPD. Design, Setting, and Participants:This intent-to-treat study was a randomized clinical trial performed at 33 US and Canadian neonatal intensive care units. Participants included 451 neonates younger than 30 weeks' gestation with birth weight less than 1250 g receiving mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14. Enrollment spanned from December 23, 2009, to April 23, 2012, and neurodevelopmental outcome studies were completed by April 4, 2014. Interventions:Placebo (nitrogen) or inhaled nitric oxide initiated at 20 ppm was decreased to 10 ppm between 72 and 96 hours after starting treatment and then to 5 ppm on day 10 or 11. Infants remained on the 5-ppm dose until completion of therapy (24 days). Main Outcomes and Measures:The primary outcome was the rate of survival without BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months' PMA. Results:In total, 222 infants (52.3% male [n?=?116]) received placebo, and 229 infants (50.2% male [n?=?115]) received inhaled nitric oxide. Their mean (SD) gestation was 25.6 (1.5) vs 25.6 (1.4) weeks, and their mean (SD) birth weight was 750 (164) vs 724 (160) g. Survival without BPD at 36 weeks' PMA was similar between the placebo and inhaled nitric oxide groups (31.5% [n?=?70] vs 34.9% [n?=?80]) (odds ratio, 1.17; 95% CI, 0.79-1.73). Rates for severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210]) and postnatal corticosteroid use for BPD (41.0% [91 of 222] vs 41.5% [95 of 229]) and the mean (SD) days of positive pressure respiratory support (55 [40] vs 54 [42]), oxygen therapy (88 [41] vs 91 [59]), and hospitalization (105 [37] vs 108 [54]) were equivalent between the 2 groups. No differences in the incidence of common morbidities were observed. Respiratory outcomes on discharge to home, at 1 year, and at age 18 to 24 months' PMA and neurodevelopmental assessments at 18 to 24 months' PMA did not differ between groups. Conclusions and Relevance:Inhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, appears to be safe but did not improve survival without BPD at 36 weeks' PMA or respiratory and neurodevelopmental outcomes at 18 to 24 months' PMA. Trial Registration:clinicaltrials.gov Identifier: NCT00931632.

Project description:the current worldwide outbreak of Coronavirus disease 2019 (COVID-19) due to a novel coronavirus (SARS-CoV-2) is seriously threatening the public health. The number of infected patients is continuously increasing and the need for Intensive Care Unit admission ranges from 5 to 26%. The mortality is reported to be around 3.4% with higher values for the elderly and in patients with comorbidities. Moreover, this condition is challenging the healthcare system where the outbreak reached its highest value. To date there is still no available treatment for SARS-CoV-2. Clinical and preclinical evidence suggests that nitric oxide (NO) has a beneficial effect on the coronavirus-mediated acute respiratory syndrome, and this can be related to its viricidal effect. The time from the symptoms' onset to the development of severe respiratory distress is relatively long. We hypothesize that high concentrations of inhaled NO administered during early phases of COVID-19 infection can prevent the progression of the disease. This is a multicenter randomized controlled trial. Spontaneous breathing patients admitted to the hospital for symptomatic COVID-19 infection will be eligible to enter the study. Patients in the treatment group will receive inhaled NO at high doses (140-180 parts per million) for 30 minutes, 2 sessions every day for 14 days in addition to the hospital care. Patient in the control group will receive only hospital care. The primary outcome is the percentage of patients requiring endotracheal intubation due to the progression of the disease in the first 28 days from enrollment in the study. Secondary outcomes include mortality at 28 days, proportion of negative test for SARS-CoV-2 at 7 days and time to clinical recovery. The trial protocol has been approved at the Investigation Review Boards of Xijing Hospital (Xi'an, China) and The Partners Human Research Committee of Massachusetts General Hospital (Boston, USA) is pending. Recruitment is expected to start in March 2020. Results of this study will be published in scientific journals, presented at scientific meetings, and on related website or media in fighting this widespread contagious disease.

Project description:BackgroundThe inhaled vasodilators nitric oxide and epoprostenol may be initiated to improve oxygenation in mechanically ventilated patients with severe acute respiratory failure (ARF); however, practice patterns and head-to-head comparisons of effectiveness are unclear.Research questionWhat are the practice patterns and comparative effectiveness for inhaled nitric oxide and epoprostenol in severe ARF?Study design and methodsUsing a large US database (Premier Healthcare Database), we identified adult patients with ARF or ARDS who were mechanically ventilated and started on inhaled nitric oxide, epoprostenol, or both. Leveraging large hospital variation in the choice of initial inhaled vasodilator, we compared the effectiveness of inhaled nitric oxide with that of epoprostenol by limiting analysis to patients admitted to hospitals that exclusively used either inhaled nitric oxide or epoprostenol. The primary outcome of successful extubation was modeled using multivariate Fine-Grey competing risk (death or hospice discharge) time-to-event models.ResultsAmong 11,200 patients (303 hospitals), 6,366 patients (56.8%) received inhaled nitric oxide first, 4,720 patients (42.1%) received inhaled epoprostenol first, and 114 patients (1.0%) received both therapies on the same day. One hundred four hospitals (34.3%; 1,666 patients) exclusively used nitric oxide and 118 hospitals (38.9%; 1,812 patients) exclusively used epoprostenol. No differences were found in the likelihood of successful extubation between patients admitted to nitric oxide-only hospitals vs those admitted to epoprostenol-only hospitals (subdistribution hazard ratio, 0.97; 95% CI, 0.80-1.18). Also no differences were found in total hospital costs or death. Results were robust to multiple sensitivity analyses.InterpretationLarge variation exists in the use of initial inhaled vasodilator for respiratory failure across US hospitals. Comparative effectiveness analyses identified no differences in outcomes based on inhaled vasodilator type.

Dataset Information

Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

Publications

Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets