Trial Outcomes & Findings for A Study of AQUAVAN® Injection in the Presence of Pre-Medication in Patients Undergoing Minor Surgical Procedures (NCT NCT00209560)
NCT ID: NCT00209560
Last Updated: 2015-01-09
Results Overview
The Modified OAA/S (MOAA/S) scale is based on a validated, 6-point rating scale. Scores are not combined. Score 5 (alert) -- responds readily to name spoken in normal tone Score 4 -- Lethargic response to name spoken in normal tone Score 3 -- Responds only after name is called loudly and/or repeatedly Score 2 -- Responds only after mild prodding or shaking Score 1 -- Responds only after painful trapezius squeeze Score 0 -- Does not respond to painful trapezius squeeze
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
168 participants
Primary outcome timeframe
Sedation success was assessed at 2 minute intervals until the end of the procedure
Results posted on
2015-01-09
Participant Flow
This study recruited at 18 centers in the US during the period of 29-Oct-2004 to 24 Mar 2005.
After enrollment and before randomization all subjects, irrespective of treatment group assignment,received fentanyl citrate injection 0.5 µg/kg to 1 µg/kg(based on age)as an analgesic pretreatment 5 minutes prior to the administration of either fospropofol disodium (Also known as,LUSEDRA and formerly known as AQUAVAN) or midazolam midazolam HCl).
Participant milestones
| Measure |
Fospropofol Disodium
525 mg to 980 mg (dose based on weight and age): one initial intravenous (i.v.) bolus dose. Supplemental doses of fospropofol disodium 105 mg to 140 mg (based on weight and age) were administered as needed.
|
Midazolam
0.5 to 2 mg (dose based on weight and age): one initial i.v. bolus dose. Supplemental doses of midazolam 0.25 mg to 1 mg (based on weight and age) were administered as needed.
|
|---|---|---|
|
Overall Study
STARTED
|
121
|
42
|
|
Overall Study
COMPLETED
|
120
|
42
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Fospropofol Disodium
525 mg to 980 mg (dose based on weight and age): one initial intravenous (i.v.) bolus dose. Supplemental doses of fospropofol disodium 105 mg to 140 mg (based on weight and age) were administered as needed.
|
Midazolam
0.5 to 2 mg (dose based on weight and age): one initial i.v. bolus dose. Supplemental doses of midazolam 0.25 mg to 1 mg (based on weight and age) were administered as needed.
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
Baseline Characteristics
A Study of AQUAVAN® Injection in the Presence of Pre-Medication in Patients Undergoing Minor Surgical Procedures
Baseline characteristics by cohort
| Measure |
Fospropofol Disodium
n=121 Participants
525 mg to 980 mg (dose based on weight and age): one initial intravenous (i.v.) bolus dose. Supplemental doses of fospropofol disodium 105 mg to 140 mg (based on weight and age) were administered as needed.
|
Midazolam
n=42 Participants
0.5 to 2 mg (dose based on weight and age): one initial i.v. bolus dose. Supplemental doses of midazolam 0.25 mg to 1 mg (based on weight and age) were administered as needed.
|
Total
n=163 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.3 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
45.3 years
STANDARD_DEVIATION 11.5 • n=7 Participants
|
45.3 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
84 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
108 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
14 participants
n=5 Participants
|
3 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
19 participants
n=5 Participants
|
10 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
87 participants
n=5 Participants
|
28 participants
n=7 Participants
|
115 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Weight (kg)
<55
|
7 particpants
n=5 Participants
|
0 particpants
n=7 Participants
|
7 particpants
n=5 Participants
|
|
Weight (kg)
55 to > 80
|
41 particpants
n=5 Participants
|
14 particpants
n=7 Participants
|
55 particpants
n=5 Participants
|
|
Weight (kg)
>80
|
73 particpants
n=5 Participants
|
28 particpants
n=7 Participants
|
101 particpants
n=5 Participants
|
|
American Society of Anesthesiologists Status (ASA)
I (A normal healthy patient)
|
48 particpants
n=5 Participants
|
19 particpants
n=7 Participants
|
67 particpants
n=5 Participants
|
|
American Society of Anesthesiologists Status (ASA)
II (A patient with mild systemic disease)
|
71 particpants
n=5 Participants
|
21 particpants
n=7 Participants
|
92 particpants
n=5 Participants
|
|
American Society of Anesthesiologists Status (ASA)
III (A patient with severe systemic disease)
|
2 particpants
n=5 Participants
|
2 particpants
n=7 Participants
|
4 particpants
n=5 Participants
|
|
History of Adverse Reactions following a Previous Sedation
Yes
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
History of Adverse Reactions following a Previous Sedation
No
|
111 participants
n=5 Participants
|
37 participants
n=7 Participants
|
148 participants
n=5 Participants
|
|
History of Adverse Reactions following a Previous Sedation
No history of sedation
|
7 participants
n=5 Participants
|
3 participants
n=7 Participants
|
10 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Sedation success was assessed at 2 minute intervals until the end of the procedurePopulation: The pP1 and mITT population included all subjects randomized,received either fospropofol disodium or midazolam, had at least 1 postdose clinical assessment, and were not terminated due to the Investigator's decision for nonstudy drug related findings. A 95% confidence interval for the sedation success rate was calculated for each treatment group.
The Modified OAA/S (MOAA/S) scale is based on a validated, 6-point rating scale. Scores are not combined. Score 5 (alert) -- responds readily to name spoken in normal tone Score 4 -- Lethargic response to name spoken in normal tone Score 3 -- Responds only after name is called loudly and/or repeatedly Score 2 -- Responds only after mild prodding or shaking Score 1 -- Responds only after painful trapezius squeeze Score 0 -- Does not respond to painful trapezius squeeze
Outcome measures
| Measure |
Fospropofol Disodium
n=121 Participants
525 mg to 980 mg (dose based on weight and age): one initial intravenous (i.v.) bolus dose. Supplemental doses of fospropofol disodium 105 mg to 140 mg (based on weight and age) were administered as needed.
|
Midazolam
n=42 Participants
0.5 to 2 mg (dose based on weight and age): one initial i.v. bolus dose. Supplemental doses of midazolam 0.25 mg to 1 mg (based on weight and age) were administered as needed.
|
|---|---|---|
|
Successful Sedation of Subjects, Defined for a Subject as Having 3 Consecutive Scores ≤ 4 on the Modified Observer's Assessment of Alertness/Sedation Scale and Completing the Procedure w/o Alternative Sedative Medications/w/o Manual/Mechanical Ventilation
pPI Population Sedation Success
|
94.2 participants
95% Confidence Interval 94.2 • Interval 88.4 to 97.6
|
78.6 participants
Interval 63.2 to 89.7
|
|
Successful Sedation of Subjects, Defined for a Subject as Having 3 Consecutive Scores ≤ 4 on the Modified Observer's Assessment of Alertness/Sedation Scale and Completing the Procedure w/o Alternative Sedative Medications/w/o Manual/Mechanical Ventilation
mITT Population Sedation Success
|
94.2 participants
Interval 88.4 to 97.6
|
78.6 participants
Interval 63.2 to 89.7
|
SECONDARY outcome
Timeframe: At 2-minute intervals from the end of the procedure until the subject met the criteria for Fully Alert statusPopulation: The primary analysis for the secondary efficacy endpoint was based on the mITT population. Missing values or incomplete data were not imputed.
Time to Fully Alert, defined as the time to the first of 3 consecutive Modified OAA/S scores of 5 from the end of the surgical procedure, was summarized.
Outcome measures
| Measure |
Fospropofol Disodium
n=120 Participants
525 mg to 980 mg (dose based on weight and age): one initial intravenous (i.v.) bolus dose. Supplemental doses of fospropofol disodium 105 mg to 140 mg (based on weight and age) were administered as needed.
|
Midazolam
n=42 Participants
0.5 to 2 mg (dose based on weight and age): one initial i.v. bolus dose. Supplemental doses of midazolam 0.25 mg to 1 mg (based on weight and age) were administered as needed.
|
|---|---|---|
|
Time to Fully Alert From the End of the Procedure
|
8.4 minutes
Standard Deviation 10.9
|
4.1 minutes
Standard Deviation 5.4
|
Adverse Events
Fospropofol Disodium
Serious events: 1 serious events
Other events: 104 other events
Deaths: 0 deaths
Midazolam
Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fospropofol Disodium
n=121 participants at risk
525 mg to 980 mg (dose based on weight and age): one initial intravenous (i.v.) bolus dose. Supplemental doses of fospropofol disodium 105 mg to 140 mg (based on weight and age) were administered as needed.
|
Midazolam
n=42 participants at risk
0.5 to 2 mg (dose based on weight and age): one initial i.v. bolus dose. Supplemental doses of midazolam 0.25 mg to 1 mg (based on weight and age) were administered as needed.
|
|---|---|---|
|
Infections and infestations
Appendictis
|
0.83%
1/121 • Number of events 1
|
0.00%
0/42
|
Other adverse events
| Measure |
Fospropofol Disodium
n=121 participants at risk
525 mg to 980 mg (dose based on weight and age): one initial intravenous (i.v.) bolus dose. Supplemental doses of fospropofol disodium 105 mg to 140 mg (based on weight and age) were administered as needed.
|
Midazolam
n=42 participants at risk
0.5 to 2 mg (dose based on weight and age): one initial i.v. bolus dose. Supplemental doses of midazolam 0.25 mg to 1 mg (based on weight and age) were administered as needed.
|
|---|---|---|
|
Gastrointestinal disorders
Anal discomfort
|
2.5%
3/121
|
0.00%
0/42
|
|
Gastrointestinal disorders
Constipation
|
4.1%
5/121
|
4.8%
2/42
|
|
Gastrointestinal disorders
Nausea
|
15.7%
19/121
|
16.7%
7/42
|
|
Gastrointestinal disorders
Pruritus ani
|
2.5%
3/121
|
0.00%
0/42
|
|
Gastrointestinal disorders
Vomiting
|
5.8%
7/121
|
7.1%
3/42
|
|
General disorders
Chills
|
1.7%
2/121
|
0.00%
0/42
|
|
General disorders
Pain
|
5.0%
6/121
|
7.1%
3/42
|
|
Injury, poisoning and procedural complications
Incision site complication
|
4.1%
5/121
|
14.3%
6/42
|
|
Injury, poisoning and procedural complications
Post procedural pain
|
52.1%
63/121
|
42.9%
18/42
|
|
Injury, poisoning and procedural complications
Procedural complication
|
9.9%
12/121
|
7.1%
3/42
|
|
Investigations
Alanine aminotransfersase increased
|
3.3%
4/121
|
0.00%
0/42
|
|
Investigations
Aspartate aminotransferase increased
|
2.5%
3/121
|
0.00%
0/42
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.5%
3/121
|
0.00%
0/42
|
|
General disorders
Hepatic enzyme increased
|
4.1%
5/121
|
0.00%
0/42
|
|
General disorders
White blood cell count increased
|
1.7%
2/121
|
0.00%
0/42
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.4%
9/121
|
4.8%
2/42
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.1%
11/121
|
11.9%
5/42
|
|
Nervous system disorders
Burning sensation
|
1.7%
2/121
|
0.00%
0/42
|
|
Nervous system disorders
Dizziness
|
3.3%
4/121
|
0.00%
0/42
|
|
Nervous system disorders
Dysgeusia
|
1.7%
2/121
|
0.00%
0/42
|
|
Nervous system disorders
Headache
|
5.0%
6/121
|
0.00%
0/42
|
|
Nervous system disorders
Paraesthesia
|
15.7%
19/121
|
2.4%
1/42
|
|
Reproductive system and breast disorders
Genital burning sensation
|
5.8%
7/121
|
0.00%
0/42
|
|
Reproductive system and breast disorders
Paraesthesia of genital female
|
1.7%
2/121
|
0.00%
0/42
|
|
Reproductive system and breast disorders
Pruritus genital
|
4.1%
5/121
|
0.00%
0/42
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
19.0%
23/121
|
0.00%
0/42
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
17.4%
21/121
|
0.00%
0/42
|
|
Skin and subcutaneous tissue disorders
Pruritus generalized
|
4.1%
5/121
|
0.00%
0/42
|
|
Vascular disorders
Hypotension
|
3.3%
4/121
|
0.00%
0/42
|
Additional Information
Eisai Medical Services
Eisai Inc
Phone: 1-888-422-4743
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place