Beyond mortality: future clinical research in acute lung injury

Abstract

Mortality in National Heart, Lung and Blood Institute-sponsored clinical trials of treatments for acute lung injury (ALI) has decreased dramatically during the past two decades. As a consequence, design of such trials based on a mortality outcome requires ever-increasing numbers of patients. Recognizing that advances in clinical trial design might be applicable to these trials and might allow trials with fewer patients, the National Heart, Lung and Blood Institute convened a workshop of extramural experts from several disciplines. The workshop assessed the current state of clinical research addressing ALI, identified research needs, and recommended: (1) continued performance of trials evaluating treatments of patients with ALI; (2) development of strategies to perform ALI prevention trials; (3) observational studies of patients without ALI undergoing prolonged mechanical ventilation; and (4) development of a standardized format for reporting methods, endpoints, and results of ALI trials.

Figure 1.

Observed 60-day mortality reported for the NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network studies. Study dates are the midpoint of the patient accrual periods. Acute Respiratory Distress Syndrome Management with Lower versus Higher Tidal Volume (ARMA); ARMA-6 and ARMA-12 are groups receiving 6 or 12 ml tidal volume/kg predicted body weight (3). Data for Assessment of Low tidal Volume and Elevated End-expiratory Volume to Obviate Lung Injury (ALVEOLI) (4), Fluid and Catheter Treatment Trial (FACTT) (5), Albuterol for the Treatment of ALI (ALTA) (52), and Omega-3 Fatty Acid, Gamma-Linolenic Acid, and Antioxidant Supplementation in the Management of ALI or ARDS (OMEGA) (53) were obtained from the study reports. Studies included a total of 2,944 patients. ARDS Network studies that are not included had significant coenrollment with the studies shown. The reduction in mortality remains significant if ARMA-12 is excluded from the analysis.

Figure 2.

Actual and projected number of noncardiac surgery, mechanically ventilated patients in Ontario, 1992 through 2026, based on actual data for 1992 and 2000 and projections, by 5-year interval, from 2006 to 2026. Projections were derived using direct standardization of the age-specific and sex-specific incidence of mechanical ventilation in 2000 and three population (pop.) growth scenarios from Statistics Canada and one scenario with both low population growth and a 20% decrease in incidence for 85 years and older and a 10% decrease for 75- to 84-year-old Ontario residents. (Reproduced with permission from Reference 32.)