Comparison of AQUAVAN® Injection to DISOPRIVAN® Injectable Emulsion for Anesthesia During Coronary Artery Surgery

Coronary Artery Bypass Surgery Clinical Trial

Official title:

Phase 2, Randomized Study of AQUAVAN® Injection In Elective Coronary Artery Surgery With Comparison to DISOPRIVAN® Injectable Emulsion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00209521
• Other study ID #: 3000-0104
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2005
• Last updated: June 10, 2010
• Start date: June 2002
• Est. completion date: July 2003

Study information

• Verified date: June 2010
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is an exploratory clinical trial designed to examine the efficacy, safety and tolerability of fospropofol (AQUAVAN) Injection compared to propofol (DISOPRIVAN) Injectable Emulsion when used to preoperatively sedate, induce, and maintain general anesthesia and to postoperatively sedate patients undergoing elective coronary artery surgery.

Description:

This Phase 2, open-label, single-center, randomized clinical trial was designed to examine the efficacy and tolerability of AQUAVAN® Injection (hereafter, referred to as AQUAVAN) when used to preoperatively sedate, induce, and maintain general anesthesia and to postoperatively sedate patients undergoing elective coronary artery surgery. Eligible patients were randomized to either AQUAVAN or DISOPRIVAN® Injectable Emulsion (hereafter, referred to as DISOPRIVAN) following screening and prior to their arrival in the surgical suite.

On the day of surgery, after the administration a 0.5 mg/kg bolus dose of lignocaine, preoperative sedation began using the target-controlled infusion (TCI) system to target desired sedation plasma concentrations of either AQUAVAN or DISOPRIVAN, depending on the randomization schedule.

The Bispectral (BIS) Index was used to guide study drug administration; target BIS ranges were 60 to 80 for sedation and 40 to 60 for the maintenance of anesthesia. Adequate sedative/hypnotic effect during surgical anesthesia was characterized by the portion of time within the target BIS Index range versus total surgical time. Following this, during postsurgical sedation, inadequate sedative/hypnotic effect was characterized by the number, duration, and magnitude of BIS scores outside of the target range versus total postsurgical sedation time. During postsurgical sedation, the Modified Ramsey Scale was used as an additional clinical tool to evaluate the state of sedation, with an attempt to maintain the score between 3 and 5.

The overall quality of induction, maintenance and ease of control of anesthesia, and quality of sedation before and during cardiopulmonary bypass (CPB), were each graded by the anesthesiologist.

Continuous monitoring of blood pressure and heart rate were used to assess the hemodynamic effect of study drug. Hypertension and hypotension were defined as excursions of >/= 20% from the baseline value.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 2003
• Est. primary completion date: July 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients were between the ages of 21 and 70 years, inclusive.

2. Patients were scheduled for first-time elective coronary artery bypass graft surgery, with 1 to 4 grafts planned.

3. Patients had an American Society of Anesthesiologists (ASA) Physical Classification System status of II or III.

4. Patients had a "good" left ventricular function as defined by a cardiac ejection fraction >=50% measured by cardiac catheterization or other quantitative technique.

5. Patients provided written Informed Consent after receiving a full explanation of the extent and nature of the study and were willing to comply with the study procedures.

6. Patients, if female, were surgically sterile or postmenopausal.

Exclusion Criteria:

1. Patient had prior coronary bypass grafting or other cardiac surgery.

2. Patient had uncontrolled hypertension (diastolic >110 mm Hg) or required additional intervention while hospitalized prior to surgery to control blood pressure.

3. Patient had a medical history of renal disease or creatinine >1.4 mg/dL.

4. Patient had known hemodynamically significant valvular abnormalities, except Grade 1 tricuspid or mitral insufficiency.

5. Patient had severe obesity, defined as a body mass index (BMI) >35.

6. Patient failed the Allen's Test to confirm the patency of the ulnar artery.

7. Patient had severe or uncontrolled systemic illness (e.g., pulmonary disease, cancer, endocrine abnormalities).

8. Patient had insulin-dependent diabetes.

9. Patient had a history of stroke or current neurological disease (e.g., dementia, neuropathy), as determined by the Investigator.

10. Patient had anticipated difficulties with intubation, in the judgment of the Investigator.

11. Patient had a history of alcohol abuse, as determined by the Investigator;

12. Patient had participated in an investigational drug study within 1 month prior to study start.

13. Patient had donated >300 mL of blood within 1 month prior to study start.

14. Patient had a positive medical history for drug abuse.

15. Patient had a known infection with human immunodeficiency virus (HIV), Hepatitis B, and/or Hepatitis C.

16. Patient had any history of anxiety or psychiatric illness or was currently using antidepressants, monoamine oxidase (MAO) inhibitors, anti-anxiety medications or other drugs with central nervous system (CNS) effects prior to their preoperative hospital stay.

17. Patient had uncorrected visual problems, including cataracts, glaucoma, or any significant abnormalities found on fundoscopic examination that would interfere with visual assessment of drug safety.

18. Patient had any history of adverse reaction to any opiate or anesthetic agent.

19. Patient, if male, did not agree to use an effective method of birth control between the time of screening and end of study.

Study Design

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

Related Conditions & MeSH terms

• Coronary Artery Bypass Surgery
• Coronary Artery Disease
• Coronary Disease
• Ischemic Coronary Artery Disease
• Myocardial Ischemia

Intervention

Drug:
• fospropofol
Using a Target Controlled Infusion (TCI) system, the target plasma concentrations of propofol to be administered from AQUAVAN were 0.7 µg/mL (sedation) and 2.5 µg/mL (maintain anesthesia).
• propofol
Using a Target Controlled Infusion (TCI) system, the target plasma concentrations of propofol to be administered from Disoprivan were 1.0 µg/mL (sedation) and 3.0 µg/mL (maintain anesthesia).

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Eisai Inc.	PPD

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median time (minutes) to loss of consciousness from induction start (reported as median and range).		Day 1	No
Secondary	Median time (minutes) to induction from start of infusion (reported as median and range).		Day 1	No
Secondary	Time (minutes) to intubation from induction start (reported as median and range).		Day 1	No
Secondary	Time (minutes) to extubation from end of infusion (reported as median and range).		Day 1	No
Secondary	Time (minutes) to last suture from induction start (reported as median and range).		Day 1	No
Secondary	Time (minutes) to full awareness from end of infusion (reported as median and range).		Day 1	No
Secondary	Median time from End of Infusion to First Modified Ramsey Score of 3 (reported as median and range).		Day 1	No