Daily Ards Research Analysis
Analyzed 10 papers and selected 3 impactful papers.
Summary
Across ARDS and related respiratory distress research, a negative phase IIb RCT of defibrotide in severe COVID-19 respiratory failure clarifies that endothelial-targeted therapy was safe but clinically ineffective. Real-world perinatal studies showed antenatal corticosteroids improved late-preterm respiratory outcomes and that minimally invasive surfactant therapy outperformed INSURE in key neonatal complications.
Research Themes
- Endothelial-targeted interventions in viral respiratory failure/ARDS
- Real-world effectiveness of antenatal corticosteroids in late preterm infants
- Less-invasive surfactant delivery strategies (MIST) vs INSURE
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 randomized, double-blind, placebo-controlled trial of 150 hospitalized COVID-19 patients with respiratory failure, continuous IV defibrotide did not shorten time to clinical improvement or reduce mortality compared with placebo. Safety was comparable, with exploratory biomarker signals suggesting endothelial effects requiring confirmation.
Impact: This well-conducted negative RCT refines therapeutic strategies by demonstrating that endothelial-targeted defibrotide is safe but clinically ineffective in severe COVID-19 respiratory failure, preventing futile adoption and focusing future research.
Clinical Implications: Defibrotide should not be used routinely for severe COVID-19 respiratory failure outside trials. Biomarker signals justify mechanistic and responder-enrichment studies but do not support a change in standard care.
Key Findings
- No significant difference in median time to clinical improvement (15 vs 20 days; p=0.10)
- No difference in Day-30 (23.0% vs 22.0%) or Day-60 mortality (26.0% vs 22.0%)
- Comparable safety: serious adverse events, hypotension, and hemorrhage rates similar to placebo
- Exploratory biomarkers: greater early D-dimer reduction and lymphocyte recovery with defibrotide
Methodological Strengths
- Randomized, double-blind, placebo-controlled design with severity stratification
- Registered trial with predefined endpoints and safety monitoring
Limitations
- Phase IIb sample size may be underpowered to detect modest effects
- Biomarker analyses exploratory and require validation; no enrichment by endothelial phenotype
Future Directions: Pursue mechanistic and pharmacokinetic analyses, and design biomarker-enriched RCTs to test endothelial-targeted strategies in defined subgroups.
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.
In a nationwide Korean cohort of 53,529 late preterm infants, antenatal corticosteroid exposure was associated with reduced need for ventilatory support and oxygen therapy, and lower incidence of neonatal respiratory distress syndrome. No benefits were observed for transient tachypnea of the newborn or moderate-to-severe bronchopulmonary dysplasia.
Impact: Provides large-scale, real-world evidence supporting guideline expansion of antenatal corticosteroids for late preterm birth by demonstrating improved acute respiratory outcomes.
Clinical Implications: For women at risk of late preterm delivery, consider antenatal corticosteroids to reduce ventilatory support, oxygen therapy, and neonatal RDS, while recognizing limited impact on TTN and rare BPD.
Key Findings
- ACS exposure associated with reduced ventilatory support (RR 0.923; 95% CI 0.865-0.985)
- Reduced oxygen therapy with ACS (RR 0.827; 95% CI 0.797-0.858)
- Lower incidence of neonatal respiratory distress syndrome (RR 0.908; 95% CI 0.844-0.978)
- No significant effect on transient tachypnea of the newborn (RR 1.058; 95% CI 0.991-1.129) and rare moderate-to-severe BPD
Methodological Strengths
- Large, population-based cohort using linked national datasets
- Consistent effects across multiple prespecified respiratory outcomes
Limitations
- Observational, retrospective design susceptible to confounding and indication bias
- No long-term neurodevelopmental follow-up reported
Future Directions: Prospective studies to refine timing/dosing of ACS in late preterm and evaluate long-term neurodevelopmental and cardiometabolic 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 a retrospective cohort of 513 preterm neonates with RDS, MIST was associated with shorter duration of mechanical ventilation and lower rates of retinopathy of prematurity and sepsis compared with INSURE, with no mortality difference. Findings support MIST as a safer, less invasive surfactant strategy.
Impact: Head-to-head comparative data in a sizable cohort indicate meaningful advantages of MIST over INSURE on key neonatal outcomes, informing practice in NICUs.
Clinical Implications: Adopt MIST when feasible to deliver surfactant in preterm RDS to reduce ventilation exposure and complications such as ROP and sepsis; prospective confirmation is warranted.
Key Findings
- No significant mortality difference between MIST and INSURE
- MIST associated with shorter duration of mechanical ventilation (P=0.0001)
- Lower rates of retinopathy of prematurity with MIST (P=0.026)
- Lower sepsis rates with MIST (P=0.010)
Methodological Strengths
- Direct head-to-head comparison with a relatively large sample (n=513)
- Clinically relevant outcomes including ventilation duration and major complications
Limitations
- Retrospective, single-center design with potential selection and confounding biases
- Lack of randomization and limited adjustment for baseline differences
Future Directions: Conduct prospective, randomized trials comparing MIST vs INSURE with long-term neurodevelopmental and respiratory follow-up.
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.