Daily Ards Research Analysis
A phase 2 randomized, double-blind trial found that inhaled pegylated adrenomedullin was safe but ineffective in improving outcomes for acute respiratory distress syndrome (ARDS), prompting early futility termination. Registry data comparing venovenous ECMO in COVID-19- vs H1N1-associated ARDS showed similar acute brain injury frequency but markedly higher mortality with acute brain injury in both groups. In a prospective cohort from Nepal, antenatal corticosteroids substantially reduced neonata
Summary
A phase 2 randomized, double-blind trial found that inhaled pegylated adrenomedullin was safe but ineffective in improving outcomes for acute respiratory distress syndrome (ARDS), prompting early futility termination. Registry data comparing venovenous ECMO in COVID-19- vs H1N1-associated ARDS showed similar acute brain injury frequency but markedly higher mortality with acute brain injury in both groups. In a prospective cohort from Nepal, antenatal corticosteroids substantially reduced neonatal respiratory distress and mortality in preterm infants, reinforcing implementation in resource-limited settings.
Research Themes
- ARDS therapeutics and trial futility signals
- ECMO-related neurologic complications and outcomes
- Perinatal interventions to prevent respiratory morbidity in preterm infants
Selected Articles
1. Safety and efficacy of inhaled PEG-ADM in ARDS patients: a randomised controlled trial.
In a multicenter phase 2 randomized, double-blind trial (n=90), inhaled pegylated adrenomedullin showed safety comparable to placebo but did not improve a composite clinical utility index or 28-day ventilator-free survival. Mortality and ongoing ventilation at days 28 and 60 were not different; the trial was stopped early for futility.
Impact: Provides rigorous negative evidence against a biologically plausible ARDS therapy, redirecting resources and future trials away from an ineffective intervention.
Clinical Implications: Do not adopt inhaled pegylated adrenomedullin for ARDS outside research. Focus clinical practice on proven supportive strategies and consider phenotypic enrichment in future trials.
Key Findings
- Both PEG-ADM doses were well tolerated with adverse events similar to placebo.
- No improvement in the composite clinical utility index was observed versus placebo.
- 28-day ventilator-free survival was lower in the 960 μg group (52%) versus 1920 μg (67%) and placebo (65%).
- No significant differences in mortality or need for ongoing ventilation at days 28 and 60; early futility termination.
Methodological Strengths
- Randomized, double-blind, placebo-controlled multicenter design with trial registration (NCT04417036).
- Dose-ranging evaluation with prespecified composite physiological and clinical endpoints.
Limitations
- Phase 2 sample size (n=90) may limit power to detect modest benefits.
- Heterogeneity of ARDS etiologies and care practices could dilute treatment effects; early stopping limits longer-term assessment.
Future Directions: Consider alternative delivery or systemic dosing of adrenomedullin, phenotype-enriched enrollment, and endpoints aligned with specific ARDS subphenotypes in larger phase 3 trials.
2. Effectiveness of Antenatal Corticosteroids in reducing morbidities and mortality in Preterm neonates: Evidence from a Tertiary Level Hospital in Nepal.
In a single-center prospective cohort (n=358) of preterm infants <34 weeks, antenatal corticosteroids were associated with markedly lower risks of neonatal respiratory distress syndrome, necrotizing enterocolitis, sepsis, need for mechanical ventilation, prolonged hospitalization, and mortality. Adjusted analyses showed substantially higher odds of adverse outcomes when ACS were not given.
Impact: Provides prospective, adjusted evidence from a low-resource setting confirming the substantial benefits of antenatal corticosteroids for very preterm births.
Clinical Implications: Reinforce implementation of ACS for threatened preterm birth <34 weeks, including protocols, supply chains, and training in resource-limited hospitals to reduce respiratory morbidity and mortality.
Key Findings
- ACS exposure was linked to lower rates of RDS (21.8% vs 61.8%, p<0.001) and NEC (5.8% vs 19.7%, p<0.001).
- Non-ACS was associated with higher odds of RDS (aOR 4.181, 95% CI 2.462-7.100) and mechanical ventilation (aOR 2.266, 95% CI 1.300-3.950).
- Non-ACS was associated with increased prolonged hospitalization (aOR 3.321, 95% CI 1.957-5.638) and mortality (aOR 5.731, 95% CI 3.199-10.266).
Methodological Strengths
- Prospective cohort design with multivariable logistic regression to adjust for confounders.
- Real-world evidence from a resource-limited tertiary hospital setting.
Limitations
- Non-randomized single-center design prone to selection bias (ACS more often given with complications).
- Short-term in-hospital outcomes; long-term neurodevelopmental effects not assessed.
Future Directions: Implementation research to optimize ACS uptake, timing, and dosing in low-resource settings, and to evaluate long-term outcomes including neurodevelopment.
3. Acute Brain Injury in COVID-19 Versus Influenza A Patients on Venovenous Extracorporeal Membrane Oxygenation: A Propensity Score Matching Analysis of the Extracorporeal Life Support Organization Registry.
In a matched ELSO registry cohort (n=674), acute brain injury occurred at similar rates in COVID-19 and H1N1 ARDS patients on VV-ECMO, but hemorrhagic events were fewer in COVID-19, while overall mortality was higher. Across both etiologies, acute brain injury was associated with dramatically increased mortality.
Impact: Clarifies neurologic complication risks and their prognostic impact across major viral ARDS etiologies during VV-ECMO, informing monitoring and anticoagulation strategies.
Clinical Implications: Prioritize rigorous neuro-monitoring for ARDS patients on VV-ECMO; anticipate high mortality with ABI and consider strategies to minimize bleeding while maintaining thrombosis control.
Key Findings
- In matched analysis, ABI frequency was similar in COVID-19 (10%) vs H1N1 (12%) ARDS on VV-ECMO (aOR 0.83; p=0.53).
- COVID-19 had fewer hemorrhagic complications compared with H1N1 (aOR 0.27; p<0.001), with no difference in thrombosis (aOR 0.67; p=0.06).
- Mortality was higher in COVID-19 vs H1N1 (aOR 2.17; p<0.001).
- ABI was associated with markedly higher mortality in both groups (COVID: 94% vs 40%; H1N1: 75% vs 29%).
Methodological Strengths
- Large international registry with propensity score matching and multivariable adjustment.
- Direct comparison of two major viral ARDS etiologies on a uniform support modality (VV-ECMO).
Limitations
- Retrospective registry design with potential unmeasured confounding.
- Heterogeneity in center practices (e.g., anticoagulation protocols and neuroimaging) may affect event detection.
Future Directions: Prospective studies to standardize anticoagulation and neuro-monitoring during VV-ECMO and to identify modifiable risk factors for ABI across ARDS etiologies.