A phase-III multicenter, randomized, double-blind, controlled trial of high-dose inhaled nitric oxide in infants with acute bronchiolitis.

Purpose: In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV). Patients and Methods: Patients receiving cisplatin ≥ 70 mg/m2 for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Results: The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P < .001 for all three comparisons). Conclusion: Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.

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Inhaled nitric oxide as an adjunct to neonatal resuscitation in premature infants: a pilot, double blind, randomized controlled trial

Pediatric Research ◽

10.1038/s41390-019-0643-x ◽

2019 ◽

Vol 87 (3) ◽

pp. 523-528 ◽

Cited By ~ 1

Author(s):

Krishnamurthy Sekar ◽

Edgardo Szyld ◽

Michael McCoy ◽

Anne Wlodaver ◽

Douglas Dannaway ◽

...

Keyword(s):

Nitric Oxide ◽

Randomized Controlled Trial ◽

Premature Infants ◽

Controlled Trial ◽

Neonatal Resuscitation ◽

Inhaled Nitric Oxide ◽

Double Blind ◽

Randomized Controlled

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

Scientific Reports ◽

10.1038/s41598-020-66433-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Aviv Goldbart ◽

Inbal Golan-Tripto ◽

Giora Pillar ◽

Galit Livnat-Levanon ◽

Ori Efrati ◽

...

Keyword(s):

Nitric Oxide ◽

Clinical Score ◽

Inhaled Nitric Oxide ◽

High Dose ◽

Acute Bronchiolitis ◽

Rapid Improvement ◽

Randomized Controlled ◽

Double Blinded ◽

Nitric Oxide Therapy ◽

Respiratory Conditions

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)

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