ARDS Network (NHLBI) Studies: Successes and Challenges in ARDS Clinical Research
Section snippets
History and goal of the ARDS Network
To hasten the development of effective therapy for acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, initiated a clinical network to carry out multicenter clinical trials of ARDS treatments. The ARDS Network was established as a contract program in 1994 following a national competition.
The ARDS Network is a clinical research network of approximately 42 hospitals, organized into 12 clinical sites, and a Clinical
Ketoconazole for ALI/ARDS
Study status: Completed.
Study dates: March 1996 to February 1998.
The first clinical trial completed by the Network was a randomized, controlled trial of ketoconazole versus placebo in patients with ALI and ARDS. Ketoconazole was chosen because of its anti-inflammatory actions noted in the laboratory and because previous phase 2 clinical trials suggested benefit in patients with or at risk for ARDS. This trial was stopped early by the DSMB in January 1997 after finding ketoconazole to be
Lower tidal volume trial
Study status: Completed.
Study dates: March 1996 to July 1999.
This landmark third trial examined lower tidal volume ventilation versus a traditionally recommended larger tidal volume approach in patients with ALI. This trial was undertaken because extensive animal studies and 2 small clinical trials suggested lung stretch with larger tidal volumes may injure the lung or prevent recovery. However, 2 other clinical trials raised questions about this hypothesis, and the use of smaller tidal volumes
Late steroid rescue study: LaSRS
Study status: Completed.
Study dates: August 1997 to November 2003.
The late phase of ARDS is often characterized by excessive fibroproliferation leading to gas exchange and compliance abnormalities. Although corticosteroids are not effective in early ARDS, several case reports and uncontrolled case series and one small randomized, controlled trial suggest that corticosteroids may be useful in the management of late-phase ARDS. To test this hypothesis a randomized, double-blinded trial comparing
Lysofylline for ALI/ARDS
Study status: Completed.
Study dates: February 1998 to June 1999.
The LARMA study was a randomized, double-blind, placebo-controlled multicenter 2 × 2 factorial study wherein each patient was randomized between lisofylline and placebo. It was designed to test whether the administration of lisofylline early after the onset of ALI or ARDS would reduce mortality and morbidity. The study was stopped by the DSMB for futility at the first scheduled interim analysis. The decision was based on
ALVEOLI study
Study status: Completed.
Study dates: November 1999 to March 2002.
Prospective, Randomized, Multi-Center Trial of Higher End-Expiratory Lung Volume/Lower FiO2 versus Lower End-expiratory Lung Volume/Higher FiO2 Ventilation in Acute Lung Injury and Acute Respiratory Distress Syndrome.
This study was a prospective, randomized, controlled multicenter trial. The objective was to compare clinical outcomes of patients with ALI and ARDS treated with a higher end-expiratory lung volume/lower FiO2 versus a
Fluid and catheter treatment trial: FACTT
Study status: Completed.
Study dates: June 2000 to October 2005.
Prospective, Randomized, Multi-Center Trial of Pulmonary Artery Catheter (PAC) versus Central Venous Catheter (CVC) for Management of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) and Prospective, Randomized, Multi-Center Trial of “Fluid Conservative” versus “Fluid Liberal” Management of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).
This study examined two different strategies for
Albuterol for the treatment of ALI: ALTA
Study status: Closed.
Study dates: August 2007 to September 2008.
ALTA was a prospective, randomized trial of aerosolized albuterol versus placebo to test the safety and efficacy of aerosolized β2-adrenergic agonist therapy for improving clinical outcomes in patients with ALI. Aerosolized β2-agonist therapy was anticipated to diminish the formation of lung edema, enhance clearance of lung edema, and decrease pulmonary inflammation in patients with ALI. Because β2-agonists have been shown to
EDEN-Omega study
Study status: Open.
Study dates: November 2006.
Prospective, Randomized Trial of Initial Trophic Enteral Feeding Followed by Advancement to Full-Calorie Enteral Feeding Versus Early Advancement to Full-Calorie Enteral Feeding (http://clinicaltrials.gov/ct2/show/NCT00609180).
This trial ran simultaneously with a trial of omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation versus a comparator. The ARDSNet trial used an omega-3 and antioxidant supplement added to “usual” feeding
Statins for acutely injured lungs from sepsis: SAILS
Study status: Open.
Study dates: March 2010.
The SAILS study is a trial of rosuvastatin versus placebo comparator for the treatment of patients with ALI or ARDS. The objective is to assess the efficacy and safety of oral rosuvastatin in patients with sepsis-induced ALI. The hypothesis of this study is that pleiotropic anti-inflammatory effects of rosuvastatin therapy will improve mortality in patients with sepsis-induced ALI.
This study is a prospective, randomized, controlled multicenter trial.
References (11)
Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome. A randomized controlled trial
JAMA
(2000)The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome
N Engl J Med
(2000)- et al.
Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome
N Engl J Med
(2006) Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome
Crit Care Med
(2002)- et al.
Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome
N Engl J Med
(1998)
Cited by (46)
Significant Variability in Surrogate Informed Consent Rates in ARDS and Prevention and Early Treatment of Acute Lung Injury Network Multicenter Trials
2022, ChestCitation Excerpt :We analyzed four National Heart, Lung, and Blood Institute ARDS Network trials: Albuterol for the Treatment of Acute Lung Injury (ALTA), Early vs Delayed Enteral Nutrition in Acute Lung Injury (EDEN), Omega Nutrtion Supplement Trial in Acute Lung Injury (OMEGA), and Statins for Acutely Injured Lungs from Sepsis (SAILS) and one Prevention and Early Treatment of Acute Lung Injury (PETAL) Network trial: Reevaluation of Systemic Early Neuromuscular Blockade (ROSE).3,4
Implications of WHO COVID-19 interim guideline 2020.5 on the comprehensive care for infected persons in Africa Before, during and after clinical management of cases
2022, Scientific AfricanCitation Excerpt :The hypoxemic respiratory dysfunction associated with ARDS usually stems from intrapulmonary ventilation-perfusion mismatch or shunt that often requires mechanical ventilation using lower tidal volumes (4–8 mL/kg predicted body weight) and lower inspiratory pressure (plateau pressure <30 cm hydrogen (H2O)) [69]. The WHO guidance recommends a titration for higher positive end-expiratory pressure for patients with moderate or severe ARDS and keeping in mind potential associated risks including lung injury of increased vascular resistance [73]. Only patients with refractory hypoxaemia despite lung-protective ventilation are recommended to be referred for extracorporeal membrane oxygenation (ECMO) [19].
Nanotherapeutics in the treatment of acute respiratory distress syndrome
2021, Life SciencesCitation Excerpt :The development of several symptoms is required to ascertain the extent of the disease's severity which ultimately results in delayed therapeutic support and patient care. Despite numerous randomized controlled trials for ARDS, a handful of successful outcomes reflect the futility of the interventions [15]. The insufficiency of pharmacotherapies could be partially attributed to the impeded drug-delivery to the damaged alveoli, insufficient accumulation of drugs in the lungs, low circulation half-life, and inability to cross physiological barriers (mucus and alveolar fluid) for systemic delivery [16–18].
Lesson learnt from the abstracts of the 5th European Airway Congress 4.-7. December 2018 in Catania, Italy: Directions of learning
2018, Trends in Anaesthesia and Critical Care