Late-Breaking Clinical Trials to be presented at special session

Results from seven Late-Breaking Clinical Trials will be presented from 2 to 4:30 p.m., Tuesday, in Rooms 2001-2003, West Building (Level 2). These studies examine treatments for ventilator-associated pneumonia, cardiac surgery associated kidney injury, septic shock, idiopathic pulmonary fibrosis, smoking cessation, malignant pleural effusion and non-cystic fibrosis bronchiectasis.

Marin Kollef, MD, St. Louis, and colleagues conducted a Phase 3, double-blind, double-dummy study to assess the efficacy and safety of a fixed seven-day course of doripenem (one-gram, four-hour infusions) versus a fixed 10-day course of imipenem in adult patients with ventilator-associated pneumonia. Numerically lower cure rates and numerically higher mortality rates were seen with the shorter seven-day course of doripenem compared with the 10-day course of imipenem, with larger differences observed in subjects with creatinine clearance =150 mL/min. The study was terminated early based on a recommendation from an independent data monitoring committee.

In another double-blind, randomized controlled study from researchers in New Zealand and Australia, Shay McGuinness, MB, ChB, Auckland New Zealand, and colleagues examined whether prophylactic perioperative infusions of sodium bicarbonate could reduce the incidence of cardiac surgery associated acute kidney injury (CSA-AKI) in a subgroup of cardiac surgery patients with preoperative or perioperative risk factors for the development of CSA-AKI. Bicarbonate infusion produced an increase in the pH of both blood and urine, but this did not result in a decrease in the incidence of CSA-AKI. The researchers conclude that they cannot recommend the use of perioperative infusions of sodium bicarbonate to reduce CSA-AKI in these patients.

B. Taylor Thompson, MD, Boston, and colleagues conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of drotrecogin alfa (activated, DAA) in 1,697 adult patients with septic shock, who received either DAA or placebo for 96 hours. The primary end point was all cause mortality 28 days after randomization. At 28 days, 26.4 percent of DAA patients and 24.2 percent of placebo patients had died. By 90 days, 34.1 percent of DAA patients and 32.7 percent of placebo patients had died. Odds ratios for mortality were not significantly different in eight other predefined subgroups, including patients at increased risk of death.

The efficacy and safety of combined prednisone, azathioprine and N-acetylcysteine (NAC) as a treatment for idiopathic pulmonary fibrosis (IPF) were examined in a double-blind, placebo-controlled, randomized trial. Researchers Ganesh Raghu, MD, Seattle, and colleagues found an increased risk of mortality and hospitalizations in patients treated with a combination of prednisone, azathioprine and NAC, compared with controls treated with placebo. The study was terminated after a mean follow-up of 32 weeks with 77 patients enrolled in the three-drug regimen arm of the study and 78 enrolled in the placebo arm.

Brian J. Smith, MBBS, Woodville, South Australia, and colleagues compared the effects of varenicline tartrate and counseling, and counseling alone for smoking cessation in a 52-week randomized controlled trial involving 392 adult inpatients. At follow-up, the proportion of subjects who remained continuously abstinent was significantly greater in the varenicline group (31.1 percent) compared to the counseling-alone group (21.4 percent, p = 0.03). Significant differences between the two study arms were seen at four, 12 and 16 weeks. The most common self-reported adverse event during the 12-week treatment phase was nausea, with 16.3 percent reporting nausea in the varenicline group compared with 1.5 percent in the counseling-alone group.

The efficacy and safety of patient controlled malignant pleural effusion (MPE) drainage by indwelling pleural catheter (IPC) were compared with those of usual care (chest tube and talc slurry pleurodesis) in a randomized controlled trial involving 106 patients. Researchers Helen E. Davies, MRCP, Cardiff, United Kingdom, and colleagues found that IPC and talc slurry pleurodesis were comparably effective treatments for the relief of breathlessness in patients with MPE, with a similar pain profile over six weeks. Use of IPCs was associated with lower initial in-hospital stay.

Finally, in a 12-month, randomized, double-blind, placebo-controlled trial, David J. Serisier, MBBS, DM, South Brisbane, Queensland, Australia, and colleagues examined the efficacy and safety of low-dose erythromycin ethylsuccinate in 117 non-smoking adult patients with non-cystic fibrosis bronchiectasis. Erythromycin therapy significantly reduced protocol-defined pulmonary exacerbations), with a mean annual reduction in exacerbations per patient of approximately 0.7. Erythromycin was well-tolerated, with only one withdrawal due to a possible adverse event after six months of therapy.