Daily Ards Research Analysis
Analyzed 10 papers and selected 3 impactful papers.
Summary
Analyzed 10 papers and selected 3 impactful articles.
Selected Articles
1. Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19.
In a phase IIb double-blind RCT of 150 hospitalized patients with COVID-19 respiratory failure, continuous IV defibrotide did not shorten time to clinical improvement or reduce 30- or 60-day mortality versus placebo. Safety was comparable, with exploratory biomarker signals (early D-dimer reduction and lymphocyte recovery) suggesting endothelial effects.
Impact: This rigorously conducted, registered RCT provides definitive evidence that defibrotide does not improve clinical outcomes in severe COVID-19, while informing endothelial-targeted strategies through biomarker signals.
Clinical Implications: Defibrotide should not be used for severe COVID-19 respiratory failure outside clinical trials. Future trials may consider biomarker-enriched populations with pronounced endotheliopathy.
Key Findings
- No significant difference in time to clinical improvement: median 15.0 vs 20.0 days (p=0.10) for defibrotide vs placebo.
- No differences in 30-day (23.0% vs 22.0%) or 60-day (26.0% vs 22.0%) mortality.
- Comparable safety profiles: serious adverse events 34.0% vs 36.0%; hypotension 16.0% vs 12.0%; hemorrhage 13.0% vs 8.0%.
- Exploratory biomarkers showed greater early D-dimer reduction and lymphocyte recovery with defibrotide.
Methodological Strengths
- Randomized, double-blind, placebo-controlled phase IIb design with severity stratification.
- Prospective registration (EudraCT and ClinicalTrials.gov) and pre-specified biomarker analyses.
Limitations
- Negative primary endpoint; trial not powered for mortality or rare safety outcomes.
- Exploratory biomarker findings require external validation and may not generalize across variants and care settings.
Future Directions: Investigate pharmacokinetics/pharmacodynamics and endothelial biomarkers to identify subgroups most likely to benefit; consider timing and dosing optimization and combination strategies.
INTRODUCTION: Endothelial dysfunction is key in COVID-19 pathogenesis. This randomized, double-blind phase IIb trial investigated continuous intravenous infusion of defibrotide in patients hospitalized with SARS-CoV-2 infection and respiratory failure. METHODS: One-hundred and fifty patients were randomized (2:1) to defibrotide or placebo, stratified by disease severity (WHO COVID-19 severity scale 4/5 vs. 6). The primary endpoint was clinical improvement time (days from first improvement through Day 30). RESULTS: Median clinical improvement time was not significantly different with defibrotide versus placebo (15.0 [IQR: 0-24] vs. 20.0 [IQR: 9-25] days; p = 0.10). Day-30 (23.0% vs. 22.0%) and Day-60 (26.0% vs. 22.0%) mortality, reduction in mean fraction of inspired oxygen during treatment, and median duration of hospitalization did not differ with defibrotide versus placebo. Defibrotide demonstrated favorable safety, with no differences versus placebo in serious adverse events (34.0% vs. 36.0%), hypotension (16.0% vs. 12.0%), or hemorrhage (13.0% vs. 8.0%). Exploratory pre-specified biomarker analyses showed greater early d-dimer reduction and lymphocyte recovery with defibrotide, although these results require validation. CONCLUSION: Continuous intravenous infusion of defibrotide was safe but did not improve clinical outcomes in severe COVID-19. Further analyses will explore mechanistic actions and pharmacokinetics of defibrotide and the pathophysiology of endothelial dysfunction in COVID-19. TRIAL REGISTRATION: EudraCT identifier: 2020-001409-21. CLINICALTRIALS: gov identifier: NCT04348383.
2. Association between antenatal corticosteroid exposure and respiratory morbidities in late preterm infants: a population-based study.
Using linked national data from Korea, ACS exposure in late preterm infants was associated with lower risks of ventilatory support, oxygen therapy, and RDS despite lower birth weight and gestational age in the exposed group. No differences were seen in TTN or moderate-to-severe BPD.
Impact: This large, population-based analysis provides robust real-world evidence supporting ACS use in late preterm infants, complementing and extending findings from ALPS to routine practice.
Clinical Implications: Clinicians can consider ACS in late preterm deliveries to reduce acute respiratory morbidity, while recognizing no observed effect on TTN or moderate-to-severe BPD in this cohort.
Key Findings
- Among 53,529 late preterm infants, 11.8% were exposed to ACS.
- ACS exposure was associated with reduced ventilatory support (RR 0.923; 95% CI 0.865–0.985).
- ACS exposure was associated with reduced oxygen therapy (RR 0.827; 95% CI 0.797–0.858).
- ACS exposure was associated with reduced RDS (RR 0.908; 95% CI 0.844–0.978).
- No significant differences for TTN (RR 1.058; 95% CI 0.991–1.129) and moderate-to-severe BPD (rare).
Methodological Strengths
- Nationwide, population-based cohort with large sample size.
- Use of linked administrative and screening datasets with adjusted risk estimates.
Limitations
- Retrospective observational design with potential residual confounding.
- Moderate-to-severe BPD was rare, limiting power to detect differences.
Future Directions: Prospective studies to refine timing, dosing, and candidate selection for ACS in late preterm; evaluate long-term neurodevelopmental and pulmonary outcomes.
OBJECTIVES: The clinical benefit of antenatal corticosteroids (ACS) in late preterm infants remains uncertain despite guideline expansion after the ALPS trial. This study evaluated the association between ACS exposure and respiratory outcomes in late preterm infants using a nationwide Korean cohort. METHODS: We performed a population-based cohort study using linked National Health Insurance Service and National Health Screening Program data. Late preterm infants (34 RESULTS: Among 53,529 infants, 6,294 (11.8 %) were exposed to ACS. Despite lower birth weight and gestational age in the ACS group, exposure was associated with reduced risks of ventilatory support (RR 0.923; 95 % CI 0.865-0.985), oxygen therapy (RR 0.827; 95 % CI 0.797-0.858), and respiratory distress syndrome (RR 0.908; 95 % CI 0.844-0.978). No significant differences were observed for transient tachypnea of the newborn (TTN) (RR 1.058; 95 % CI 0.991-1.129). Moderate-to-severe bronchopulmonary dysplasia (BPD) was rare and not associated with ACS. CONCLUSIONS: In this nationwide cohort, ACS exposure was associated with improved acute respiratory outcomes in late preterm infants, except for TTN and moderate-to-severe BPD, providing real-world evidence supporting its effectiveness.
3. MIST Versus INSURE: Superior Outcomes in Surfactant Administration for Preterm Neonates with RDS.
In 513 preterm infants with RDS, MIST was associated with shorter mechanical ventilation and lower rates of ROP and sepsis compared with INSURE, with no mortality difference. These findings favor MIST as a less invasive surfactant delivery strategy.
Impact: Provides comparative effectiveness data in a sizable cohort supporting MIST over INSURE for key neonatal outcomes, aligning with evolving respiratory care practices.
Clinical Implications: Consider MIST as first-line surfactant administration for preterm RDS where expertise is available, aiming to minimize ventilation exposure and related complications.
Key Findings
- No significant mortality difference between MIST and INSURE.
- MIST associated with shorter duration of mechanical ventilation (P=0.0001).
- Lower incidence of retinopathy of prematurity with MIST (P=0.026).
- Lower incidence of sepsis with MIST (P=0.010).
Methodological Strengths
- Relatively large single-center cohort with standardized data collection.
- Direct head-to-head comparison of two widely used surfactant strategies.
Limitations
- Retrospective design with potential selection bias and unmeasured confounding.
- Single-center setting limits generalizability; long-term neurodevelopmental outcomes not assessed.
Future Directions: Prospective multicenter RCTs comparing MIST vs INSURE with standardized protocols and long-term follow-up are warranted.
INTRODUCTION: Minimally invasive surfactant therapy (MIST) is increasingly adopted in neonatal care as an alternative to the INSURE (Intubation-Surfactant-Extubation) method for managing respiratory distress syndrome (1) in preterm infants. MIST reduces intubation-related complications and facilitates surfactant administration without invasive ventilation. This study aimed to compare the complications and outcomes of surfactant delivery via MIST versus INSURE in preterm infants with RDS. METHODS: In this retrospective study, we analyzed data from 513 preterm infants (gestational age: 28-34 weeks) with RDS admitted to Ghaem Hospital, Mashhad, Iran, between 2019 and 2025. Outcomes were compared between 257 infants treated with INSURE and 256 treated with MIST. Data on gestational age, birth weight, Apgar scores (1st and 5th minute), need for mechanical ventilation, duration of oxygen therapy, and surfactant re-dosing were collected using a structured checklist. Statistical analysis was performed using SPSS v26. RESULTS: Mean gestational age was 30.9 ± 2.6 weeks. Short-term outcomes revealed no statistically significant difference in mortality between the two methods. However, the MIST group demonstrated significantly lower rates of long-term complications, including reduced duration of mechanical ventilation (P = 0.0001), retinopathy of prematurity (ROP; P = 0.026), and sepsis (P = 0.010). CONCLUSION: MIST is a safe and effective alternative to INSURE for surfactant administration in preterm infants with RDS. It is associated with improved short-term outcomes, including shorter mechanical ventilation duration and lower incidences of ROP and sepsis. These findings support MIST as a preferable approach in clinical practice.