PRECEDEX Rx

Intensive Care Unit Sedation 

Adult Patients

2 randomized, double-blind, parallel-group, placebo-controlled multicenter clinical trials (Study 1 and 2) included 754 adult patients being treated in a surgical intensive care unit. All patients were initially intubated and received mechanical ventilation. These trials evaluated the sedative properties of Precedex by comparing the amount of rescue medication (midazolam in one trial and propofol in the second) required to achieve a specified level of sedation (using the standardized Ramsay Sedation Scale) between Precedex and placebo from onset of treatment to extubation or to a total treatment duration of 24 hours. 

Study 1

• Adult patients were randomly assigned to receive placebo (n=175) or Precedex (n=178) by intravenous (IV) infusion at a dose of 0.4 mcg/kg/hr (with allowed adjustment between 0.2 and 0.7 mcg/kg/hr after an initial loading dose of 1 mcg/kg IV over 10 minutes. The study drug infusion rate was adjusted to maintain a Ramsay sedation score of ≥3. Patients were allowed to receive “rescue” midazolam as needed to augment the study drug infusion. Midazolam was used significantly more among patients in the placebo arm compared with those in the Precedex arm.

• In a second prospective primary analysis, the sedative effects of Precedex were compared with the percentage of adult patients who achieved a Ramsay sedation score of ≥3 during intubation without the use of additional rescue medication. A significantly greater percentage of adult patients in the Precedex arm maintained a Ramsay sedation score of ≥3 without receiving any midazolam rescue compared to the placebo arm.

• In a prospective secondary analysis, a dose of morphine sulfate was assessed among adults in the Precedex and placebo arms. Patients in the Precedex arm received less morphine sulfate for pain  compared with those in the placebo arm. Moreover, there was a greater proportion of Precedex-treated patients who received no morphine sulfate for pain compared with placebo-treated patients (44% vs 19%, respectively).

Study 2

• Adult patients were randomly assigned to receive placebo (n=198) or Precedex (n=203) by IV infusion at a dose of 0.4 mcg/kg/hr (with allowed adjustment between 0.2 and 0.7 mcg/kg/hr after an initial loading dose of 1 mcg/kg IV over 10 minutes. The study drug infusion rate was adjusted to maintain a Ramsay sedation score of ≥3. Patients were allowed to receive “rescue” propofol as needed to augment the study drug infusion. 

• Propofol was used significantly more among patients in the placebo arm compared with those in the Precedex arm. 

• A significantly greater percentage of adult patients in the Precedex group compared to the placebo group maintained a Ramsay sedation score of ≥3 without receiving any propofol rescue.

• In a prospective secondary analysis, a dose of morphine sulfate was assessed among adults in the Precedex and placebo arms. Patients in the Precedex arm received less morphine sulfate for pain  compared with those in the placebo arm. Moreover, there was a greater proportion of Precedex-treated patients who received no morphine sulfate for pain compared with placebo-treated patients (41% vs 15%, respectively).

A controlled clinical trial also compared Precedex to midazolam in ICU sedation exceeding 24 hours duration. Precedex did not achieve superiority to midazolam for the primary efficacy endpoint of the percentage of time patients were adequately sedated (81% vs 81%).

Procedural Sedation

Adult Patients

2 randomized, double-blind, placebo-controlled multicenter clinical trials (Study 1 and 2) evaluated the efficacy and safety of Precedex for sedation of non-intubated adults prior to and/or during surgical and other procedures.

Study 1

• Study 1 evaluated the sedative properties of Precedex in adults having a variety of elective surgeries/procedures performed under monitored anesthesia care.

• The sedative properties of Precedex were evaluated by comparing the percent of adult patients not requiring rescue midazolam to achieve a specified level of sedation using the standardized Observer’s Assessment of Alertness/Sedation Scale. Patients were randomly assigned to receive a loading infusion of either Precedex 1 mcg/kg, Precedex 0.5 mcg/kg, or placebo (normal saline) given over 10 minutes and followed by a maintenance infusion started at 0.6 mcg/kg/hr. 

• Precedex was more effective than the comparator arm when used to sedate non-intubated patients requiring monitored anesthesia care during surgical and other procedures.

Study 2

• Study 2 evaluated Precedex in adults undergoing awake fiberoptic intubation prior to a surgical or diagnostic procedure. The sedative properties of Precedex were evaluated by comparing the percent of adult patients requiring rescue midazolam to achieve or maintain a specified level of sedation using the Ramsay Sedation Scale score ≥2. 

• Patients were randomly assigned to receive a loading infusion of Precedex 1 mcg/kg or placebo (normal saline) given over 10 minutes and followed by a fixed maintenance infusion of 0.7 mcg/kg/hr. After achieving the desired level of sedation, topicalization of the airway occurred. Adult patients were allowed to receive rescue midazolam as needed to achieve and/or maintain a Ramsay Sedation Scale ≥2.  

•  A significantly greater percentage of adult patients in the Precedex arm maintained a Ramsay sedation score of ≥2 without receiving any midazolam rescue compared to the placebo arm (53% vs 14%).

Pediatric Patients  

• A randomized, double-blind, dose-ranging, dose-controlled multicenter clinical trial evaluated the efficacy and safety of Precedex for sedation of 122 non-intubated pediatric patients aged 1 month to less than 17 years undergoing MRI scans.

• Patients were randomly assigned to receive Precedex low dose, middle dose, or high dose. All patients received a loading dose infusion of Precedex over 10 minutes followed by a maintenance infusion for the duration of the MRI scan. Patients were allowed to receive concomitant propofol if needed based on clinical judgement to achieve and/or maintain adequate sedation.

• In the combined age group, 14.3% (6/42) of pediatric patients in the low dose group did not require concomitant propofol vs 63.2% (24/38) in the high dose group. The percentage of patients at the Precedex high dose who completed the MRI without concomitant propofol was statistically greater than the percentage in the Precedex low dose group (P <.001). 

• In the Precedex high dose group, pediatric patients in both the combined and individual age group were at the target sedation rating scale score (PSSS of 2) for a mean >87% of the time during the Precedex maintenance infusion. In both the combined and individual age group, an increase in the percentage of time at the target sedation rating scale score (PSSS of 2) was observed with increasing Precedex dosage.