Inhaled corticosteroids in transient tachypnea of the newborn: A randomized, placebo-controlled study
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Design
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Randomized, double-blind, placebo-controlled, multicenter study
N= 49
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Objective
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To determine if early inhaled corticosteroids could alleviate the respiratory distress and morbidity in late preterm and term neonates with transient tachypnea of the newborn (TTN)
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Study Groups
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Budesonide (n= 24)
Placebo (n= 25)
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Inclusion Criteria
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Post-menstrual age (PMA) ≥34 weeks, onset of tachypnea (respiratory rate [RR] ≥60 breaths/minute) within 6 hours of birth, tachypnea persisting ≥4 hours, chest radiograph with evidence of lung edema
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Exclusion Criteria
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Patients with respiratory distress syndrome, congenital heart disease, meconium aspiration syndrome, non-respiratory disorders causing tachypnea, pneumonia, suspected sepsis/bacteremia, and evidence of prenatal steroid use |
Methods
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Patients were randomized to receive 2 mL of either inhaled budesonide (1,000 mcg) or placebo (0.9% normal saline solution) via nebulization through a face mask at a flow rate of 5 L/minute. The first dose was administered within the first 6 hours of birth, and a second dose was given 12 hours after the first administration.
Clinical assessment before the first dose included RR, heart rate (HR), the fraction of inspired O2 (FiO2) to keep O2 saturation within desired range, and respiratory support level; labs at baseline included complete blood count, venous blood gas, and immature to total neutrophil count, and blood glucose levels. Clinical assessments with RR, HR, and FiO2 were conducted every 2 hours during the first 48 hours following drug administration or until respiratory distress resolved. TTN clinical score was assessed after 12 hours before second dose, as well as at 24 and 48 hours following study entry. Target oxygen saturation by pulse oximetry (SpO2) levels for patients >37 weeks PMA was >95%, and >92% in patients 34 to 36 weeks PMA.
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Duration
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Enrollment: March 2012 to June 2016
Intervention: 12 hours
Follow-up: Monitored 12, 24, and 48 hours following first dose
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Outcome Measures
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Assessment of respiratory distress by TTN clinical score, RR, HR, and FiO2 to target SpO2 compared to placebo at 12, 24, and 48 hours following first dose of inhaled study medication
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Baseline Characteristics
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Budesonide (n= 24)
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Placebo (n= 25)
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Gestational age, weeks
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36.8 ± 1.9 |
36.4 ± 1.8 |
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Age at enrollment, hours
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6.25 ± 2.8 |
6.28 ± 2.5 |
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Male
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20 (83%) |
17 (68%) |
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Baseline clinical assessment
RR, breath/minute
HR, beats/minute
SpO2, %
FiO2
TTN clinical score
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73.6 ± 27.3
140 ± 19.1
95.7 ± 3.7
0.30 ± 0.10
4.3 ± 1.6
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77.5 ± 24.8
135.2 ± 20.2
96.9 ± 3.5
0.29 ± 0.10
4.1 ± 2.1
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O2 or respiratory support
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24 (100%) |
25 (100%) |
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Results
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Endpoint
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Budesonide (n= 24)
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Placebo (n= 25)
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p-value
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TTN clinical score
at 12 hours
at 24 hours
at 48 hours
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1.9 ± 1.8
1.2 ± 1.5
0.5 ± 0.9
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1.5 ± 1.7
1.3 ± 1.6
0.6 ± 1
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0.4
0.8
0.63
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RR, breath/minute
at 12 hours
at 24 hours
at 48 hours
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62.3 ± 21.4
58.4 ± 18.1
56.3 ± 22
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62.6 ± 20.6
58.5 ± 22.4
56.1 ± 22.5
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0.94
0.98
0.99
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HR, beats/minute
at 12 hours
at 24 hours
at 48 hours
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139.1 ± 13.4
146.5 ± 15.2
138 ± 13.7
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144.8 ± 14
143 ± 16.2
139.7 ± 15.7
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0.15
0.45
0.71
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SpO2, %
at 12 hours
at 24 hours
at 48 hours
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97.1 ± 2.8
96.1 ± 3.1
95.4 ± 8.2
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97.3 ± 3.23
97.6 ± 2
97.8 ± 2.2
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0.86
0.07
0.19
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FiO2
at 12 hours
at 24 hours
at 48 hours
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0.27 ± 0.1
0.3 ± 0.1
0.3 ± 0.2
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0.3 ± 0.1
0.3 ± 0.1
0.3 ± 0.1
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0.85
0.33
0.71
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O2 or respiratory support at 48 h
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9 (37%)
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11 (44%)
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1
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Adverse Events
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No short-term adverse events were reported.
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Study Author Conclusions
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We conclude that our pilot study was unable to detect a significant effect of inhaled budesonide on the respiratory course of TTN in late preterm and term infants. We detected no short-term adverse outcomes.
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InpharmD Researcher Critique
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This study was conducted in both late pre-term and at-term neonates, and as such the adverse effects of inhaled budesonide on pre-term neonate populations have not been fully investigated. No adverse events with the use of inhaled budesonide were seen within this study. However, the small sample size did not allow for the identification of any uncommon adverse events. Adrenal suppression was not evaluated or mentioned by investigators.
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