Hospira's Precedex Phase IV Study Published in the Journal of the American Medical Association
- Precedex-Sedated Patients Studied For Greater Than 24 Hours in ICU -
LAKE FOREST, Ill., February 02, 2009 /PRNewswire-FirstCall/ -- The Journal of the American Medical Association (JAMA) has published study results demonstrating <!-- cpurl -->Hospira<!-- /cpurl -->, Inc.'s alpha-2 agonist <!-- ppurl -->Precedex <!-- /ppurl -->(dexmedetomidine hydrochloride) for intravenous sedation provides comparable effectiveness to commonly used gamma-aminobutyric acid (GABA)-agonist midazolam for greater-than-24-hour sedation of mechanically ventilated patients in the intensive care unit (ICU).
According to the journal article, study results also showed that patients sedated with Precedex were removed from mechanical ventilation almost two days earlier, and the prevalence of delirium in Precedex-treated patients was 22.6 percent less than in patients treated with midazolam. These study conclusions appear in the Feb. 4 issue of JAMA.
The prospective, double-blind, randomized, multinational, comparator Phase IV trial was conducted from March 2005 through August 2007 and involved 375 medical/surgical ICU patients expected to require mechanical ventilation for more than 24 hours. As measured using the Richmond Agitation-Sedation Scale (RASS), there was no difference between Precedex and midazolam in time at targeted sedation level, the study's primary endpoint. Patients in the Precedex group spent 77.3 percent of the time within the target RASS range, while patients in the midazolam group spent 75.1 percent of the time in the target range. These results were based on the intent-to-treat population. This trial forms the basis of a supplemental NDA that has been submitted to the U.S. Food and Drug Administration (FDA) seeking approval for the use of Precedex for sedation of patients beyond 24 hours in the intensive care setting.
According to the article published in JAMA, the incidence of delirium during treatment among patients was 54 percent in Precedex-treated patients vs. 76.6 percent in midazolam-treated patients. Median time to removal from mechanical ventilation was 3.7 days in the Precedex-treated patients vs. 5.6 days in the midazolam-treated patients, a difference of 44 hours. Precedex-treated patients were more likely to develop bradycardia, or slow heartbeat, but had a lower likelihood of tachycardia (fast heartbeat) or hypertension that required treatment.
The study design used in this phase IV trial incorporated new standard elements of sedation practice, including a light-to-moderate sedation target, delirium assessment, and study drug titration or interruption every four hours and as part of a daily arousal assessment.
"This multicenter study is one of the largest to compare two different sedatives for use in the ICU in a randomized and blinded design," said Richard R. Riker, M.D., director of critical care research, Division Pulmonary and Critical Care Medicine, Maine Medical Center. "Patients who received Precedex were extubated sooner and had a lower prevalence of delirium. I expect that patients requiring long-term sedation, their families and healthcare providers will welcome the results of this trial."
There are more than 5 million patients treated annually in the ICU(1). In 2003, there were nearly 300,000 prolonged mechanical ventilation discharges in the United States at an annual aggregated hospital cost of more than $16 billion. At a cost of more than $1,500 per patient-day(2), mechanical ventilation represents a significant contribution to overall expenses in the intensive care setting and drives a disproportionate share of resource utilization.
Providing sedation for patient safety and comfort is an integral component of bedside care for nearly every patient in the ICU, and practice guidelines for sedation in the ICU have identified the need for well-designed randomized trials comparing the effectiveness of different sedative agents for important clinical outcomes.
"Through this clinical research for Precedex, Hospira is working to provide nurses, physicians and pharmacists with data to support a potential new sedation strategy for management of these complex and critically ill patients," said Paula Bokesch, M.D., global medical director, Global Medical Affairs - Drug Development, Hospira. "Hospira is committed to the research and development of products that improve patient care."
Precedex Indications and Safety Information
Precedex (dexmedetomidine hydrochloride) is Hospira's proprietary I.V. sedative, and it is a relatively selective alpha-2-adrenoceptor agonist. In the United States, it is the only drug in its class (alpha-2-agonists) approved for continuous I.V. sedation of initially intubated and mechanically ventilated patients in the intensive care setting for use up to 24 hours. It can be used before, during and after extubation.
Due to the known pharmacological effects, patients should be continuously monitored while receiving Precedex. Precedex should only be administered by persons skilled in the management of patients in the intensive care or operating room setting. Clinically significant bradycardia and sinus arrest episodes in young, healthy volunteers with high vagal tone or with different routes of administration including rapid intravenous or bolus administration have been reported. Hypotension and/or bradycardia may necessitate intervention and may be more pronounced in hypovolemic patients and in patients with diabetes mellitus, chronic hypertension, and the elderly. Co-administration with other vasodilators or negative chronotropic agents: Use with caution due to additive pharmacodynamic effects. Transient hypertension has been observed primarily during the loading dose. The most common treatment-emergent adverse reactions occurring in greater than 2 percent of patients in both intensive care unit and procedural sedation include hypotension, bradycardia, and dry mouth.
Hospira, Inc. is a global specialty pharmaceutical and medication delivery company dedicated to Advancing Wellness(TM). As the world leader in specialty generic injectable pharmaceuticals, Hospira offers one of the broadest portfolios of generic acute-care and oncology injectables, as well as integrated infusion therapy and medication management solutions. Through its products, Hospira helps improve the safety, cost and productivity of patient care. The company is headquartered in Lake Forest, Ill., and has more than 14,000 employees.
(1) Society of Critical Care Medicine. Critical Care Statistics in the United States. (2) Dasta, Joseph F., McLaughlin, Trent P., et al. Daily cost of an intensive care unit day: The contribution of mechanical ventilation. Critical Care Medicine, 2005; 33(6):1266-1271
Posted: February 2009