About the NHLBI ARDS Network

The NIH-NHLBI ARDS Network was a research network formed to study treatment of Acute Respiratory Distress Syndrome.

History

In order 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 (NIH), initiated a clinical network to carry out multi-center clinical trials of ARDS treatments. The ARDS Network was established as a contract program in 1994 and renewed in 2005 following two national competitions. The goal of the Network was to efficiently test promising agents, devices, or management strategies to improve the care of patients with ARDS. During its 20 years of service, 5,527 patients were enrolled in 10 randomized controlled trials and one observational study

In some of the most highly cited articles in critical care, network investigators reported improved survival with lung protective ventilation and shortened duration of mechanical ventilation with conservative fluid management. Additional trials informed best practices by suggesting no role for routine use of corticosteroids, beta agonists, pulmonary artery catheterization, or early full calorie enteral nutrition. The ARDS Network also developed new outcome measures (ventilator free days) and promoted innovative and efficient techniques (factorial designs and coenrollment) to speed the discovery of new treatment approaches for patients with ARDS. Comparative effectiveness trials using explicit methodology allowed other research groups to replicate and build upon the Network’s studies. Finally, through the foresight of many investigators within the Network, additional resources were obtained for the collection and analysis of biospecimens and to perform numerous ancillary studies, efforts that have advanced our understanding of the pathogenesis and natural history of ARDS. On June 30th, 2014, the Network contract came to a close. The clinical trial data and remaining biospecimens for all but the most recent ARDS Network trial (SAILS) are available to the public through BioLINCC (https://biolincc.nhlbi.nih.gov) and the SAILS data and specimens will be available in early 2015. The NHLBI-funded Prevention and Treatment of Acute Lung Injury (PETAL) Network will begin work on prevention and early treatment of ARDS. For more information, see http://petalnet.org.

ARDS

ARDS, or Acute Respiratory Distress Syndrome, is an inflammatory lung condition involving both lungs that may complicate severe pneumonia (including influenza), trauma, sepsis, aspiration of gastric contents, and many other conditions. Inflammation leads to injury of lung tissue and leakage of blood and plasma into the airspaces resulting in low oxygen levels in the blood. Mechanical ventilation is required both to deliver higher concentrations of oxygen to and provide ventilation to remove carbon dioxide from the body. Inflammation in the lung may lead to inflammation elsewhere causing shock and injury or dysfunction in the kidneys, heart, and muscles.

There is no proven drug treatment for ARDS per se. Current management of ARDS begins with treatment and stabilization of the underlying disease that caused ARDS, such as early and effective antibiotics for pneumonia or sepsis. The injured lung should be managed gently with small breaths and low pressures from the ventilator (so called low tidal volume and pressure ventialtion). In addition, conservative use of intravenous fluids combined with removal of excess fluids with diruetics lessens the need for mechanical ventilation. With these supportive measures, the lung may heal quickly and the patient can return to normal breathing in days; in severe cases ARDS may enter a prolonged phase of healing that may require weeks to resolve. In even more severe cases, devastating lung injury cannot support life or other organs fail along with the lung (a condition known as multiple organ failure). Death may occur in up to 40 percent of cases in this severe form.

OHRP Investigation

Some investigators objected to the study design used by the ARDS Network arguing that the control arms of the mechanical ventilation and fluid management trials were not representative of usual care. They brought their complaint to the Office of Human Research Protections (OHRP). In response, Network investigators argued that usual ICU care included many approaches to mechanical ventilation and fluid management and that the control arms were indeed well represented in usual care practices at the time. Further, usual care included widely different practices as clinicians did not have reliable evidence pointing them towards what may be best approach or best practice. This was the very reason these studies were needed.

On July 3, 2003 the OHRP published its determinations from the subsequent inquiry. In its most important finding, OHRP said “… almost all of the consultants engaged by OHRP opined that risks to subjects in the ARMA [tidal volume] trial were minimized and reasonable in relation to anticipated benefits to the subjects and the importance of the knowledge that was expected to result.” The OHRP consultants expressed the same opinion regarding the ARDS Network fluids and catheters treatment trial (FACTT). The OHRP consultants’ findings were consistent with those of the 5 independent consultants engaged by the NHLBI who, on August 30, 2002 concluded unanimously that the ARDS Network trials were safe and appropriately designed. The OHRP determination letter requested that all IRBs review additional background materials pertinent to the FACTT study, examine their practices, and requested changes to the FACTT consent forms. FACTT was resumed without changes to the trial design or procedures after these actions were completed.