Midazolam Used Alone or Sequential Use of Midazolam and Propofol/Dexmedetomidine in Mechanically Ventilated Patients

Delirium Clinical Trial

Official title:

Midazolam Used Alone or Sequential Use of Midazolam and Propofol/Dexmedetomidine for Long-Term Sedation in Critically Ill, Mechanically Ventilated Patients: a Prospective, Randomized Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02528513
• Other study ID #: HaxiICU
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: August 15, 2015
• Last updated: April 26, 2016
• Start date: December 2015
• Est. completion date: February 2017

Study information

• Verified date: April 2016
• Source: West China Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate effects, safety and cost of midazolam used alone or sequential use of midazolam and propofol/dexmedetomidine for long-term sedation in critically ill, mechanically ventilated patients.

Description:

It is well known that sedation is frequently required as a component of compassionate care in critically ill patients. Until now, there is no ideal sedation drug and every sedation drug has its advantage and disadvantage for long-term sedation in critically ill, mechanically ventilated patients. The sequential use of midazolam and propofol for long-term sedation was associated with a faster recovery, earlier extubation, shorter mechanical ventilation time and less cost of total ICU treatment compared with midazolam alone, The protocol was associated with less cost of pharmaceutical sedation compared with propofol alone. But, propofol and midazolam may cause respiratory depression and delirium. Both drugs should be stopped after the patient passed the screen of weaning from mechanical ventilation, then it would induce the stress response and agitation, it would cause prolonged sedation and delay extubation.

Dexmedetomidine is a centrally acting a2-receptor agonist, has less effect on arousability and respiratory depression. The purpose of this study was to evaluate effects, safety and cost of midazolam used alone or sequential use of midazolam and propofol/dexmedetomidine for long-term sedation in critically ill, mechanically ventilated patients.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 240
• Est. completion date: February 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Intubated patients;

2. Age=18 years old;

3. Anticipated Ventilation and sedation duration of at least 72 hours.

Exclusion Criteria:

1. Allergy to the study drug;

2. suspected pregnancy;

3. gross obesity;

4. Extremely unstable of circulatory system, such as systolic blood pressure less than 90 mm Hg despite plasma volume expansion and continuous infusions of vasopressors before the start of study drug infusion;

5. Uncontrolled abnormal hypertension, such as systolic blood pressure more than 180 mmHg or diastolic more than105 mmHg;

6. Heart rate less than 50 bpm;

7. Second or third degree heart block;

8. moribund state;

9. history of alcoholism or intake of anti-anxiety drugs or hypnotics;

10. chronic renal failure;

11. coma by cranial trauma or neurosurgery or unknown etiology or epileptic state;

12. History of neuromuscular disease;

13. unwillingness to provide informed consent by patients or their authorized surrogates following ICU admission.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Complication
• Delirium
• Mechanical Ventilation

Intervention

Drug:
• midazolam
Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to RASS score (-3 to 0).
• Fentanyl
Fentanyl is used with bolus dosage of 1-2ug/kg and maintenance dosage of 1-2ug/kg/h, with the dosage adjusted to critical care pain observation tool(CPOT)score(0-1).
• propofol
After the spontaneous breathing trial safety screen is passed, midazolam is switched to propofol, which is administered at the maintenance dosage of 0.50-3.00mg/kg/h, with the dosage adjusted to RASS score (-2 to 0).
• Dexmedetomidine
After the spontaneous breathing trial safety screen is passed, midazolam is switched to dexmedetomidine, which is administered at an infusion bolus of 0.5µg/kg over 10 min (given or not according to patients' condition) and the maintenance dosage of 0.2-0.7ug/kg/h, with the dosage adjusted to RASS score (-2 to 0).

Procedure:
• Procedure:sedation assessment
The nursing staff continuously monitored the sedation depth and adjusted the dosages of sedative and analgesic drugs to maintain the sedation target level. The sedation depth were assessed and recorded every 4 h (or more frequently when indicated).
• Procedure:Weaning
the respiratory therapists managed patients with a daily interruption of continuous sedation and the spontaneous breathing trial (SBT) protocols daily.

Drug:
• midazolam(used for passing the SBT safety screen)
After the spontaneous breathing trial safety screen is passed,in the midazolam group, midazolam will continue to be used for sedation, with the dosage adjusted to RASS score (-2 to 0).

Locations

Country	Name	City	State
China	Department of Critical care medicine of West China Hospital	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
West China Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weaning time		From sedation sequential criteria to extubation, up to 28 days	Yes
Secondary	The pharmaceutical costs of sedation		From sedation drug is used to cessation of sedation up to 28 days.	Yes
Secondary	The total ICU costs		From admitted to ICU until ventilation and participants discharged from ICU, up to 28 days.	Yes
Secondary	The incidence of delirium (patients with diagnosis of delirium/ total patients in each group × 100% )	After the daily interruption of continuous sedation,delirium is assessed by the the confusion assessment method for the diagnosis of delirium in ICU(CAM-ICU). If the patient has the clinical features of 1 and 2, or 3,or 4 in the CAM-ICU, delirium can be diagnosed.	From sedation drug is used to cessation of sedation, up to 28 days.	Yes
Secondary	Sedation satisfaction degree (The total time within target sedation level/total evaluation times ×100% )		From sedation drug is used to cessation of sedation up to 28 days.	Yes