Trial Outcomes & Findings for Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone (NCT NCT01486615)

Results Overview

VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

80 participants

Primary outcome timeframe

Change from baseline in VAS anxiety score at 15 minutes after premedication

Results posted on

2012-10-05

Participant Flow

Recruitment period was of three months. Approximately 90 minutes prior to surgery, each patient was taken to a quiet room inside the operation theater complex.

One hundred and ten patients were assessed for eligibility, 98 patients had anxiety VAS ≥3. Among them, 80 patients who met the inclusion criteria, were enrolled and assigned into four groups.

Participant milestones

Participant milestones
Measure	Melatonin Oral premedication with 3 mg melatonin tablet (Meloset) 1-2 hour prior to anesthesia	Melatonin and Alprazolam Oral premedication with a 3 mg melatonin and 0.5 mg alprazolam combination tablet (Stressnil) 1-2 hrs prior to anesthesia	Alprazolam Oral premedication with 0.5 mg alprazolam (Alprax) 1-2 hr prior to anesthesia	Placebo Oral premedication with a similar looking placebo tablet 1-2 hr prior to anesthesia
Overall Study STARTED	20	20	20	20
Overall Study COMPLETED	20	19	18	18
Overall Study NOT COMPLETED	0	1	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Melatonin n=20 Participants premedication 1-2 hour prior to anesthesia	Melatonin and Alprazolam n=20 Participants premedicated 1-2 hrs prior to anesthesia	Alprazolam n=20 Participants premedication 1-2 hr prior to anesthesia	Placebo n=20 Participants premedication 1-2 hr prior to anesthesia	Total n=80 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	20 Participants n=4 Participants	80 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age Continuous	33.8 years STANDARD_DEVIATION 10.9 • n=5 Participants	38.0 years STANDARD_DEVIATION 13.5 • n=7 Participants	36.9 years STANDARD_DEVIATION 10.0 • n=5 Participants	36.2 years STANDARD_DEVIATION 12.9 • n=4 Participants	36 years STANDARD_DEVIATION 12 • n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	15 Participants n=4 Participants	61 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	19 Participants n=21 Participants
Region of Enrollment Nepal	20 participants n=5 Participants	20 participants n=7 Participants	20 participants n=5 Participants	20 participants n=4 Participants	80 participants n=21 Participants
Vas baseline (cm)	5 centimeters n=5 Participants	5 centimeters n=7 Participants	5 centimeters n=5 Participants	5 centimeters n=4 Participants	5 centimeters n=21 Participants
Anaesthesia time	65.8 minutes STANDARD_DEVIATION 18.1 • n=5 Participants	77.2 minutes STANDARD_DEVIATION 34.3 • n=7 Participants	73.7 minutes STANDARD_DEVIATION 21.0 • n=5 Participants	71.7 minutes STANDARD_DEVIATION 17.6 • n=4 Participants	71.6 minutes STANDARD_DEVIATION 23.7 • n=21 Participants

PRIMARY outcome

Timeframe: Change from baseline in VAS anxiety score at 15 minutes after premedication

Population: sample size of 16 patients in each group was determined by a power analysis (α, 0.05; β, 0.10) assuming that there will be 50% reduction in anxiety VAS from baseline in the experimental groups and 4% in the placebo group. To compensate for dropout cases and shifting from normality in data distribution, 20 cases were studied in each group.

VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=20 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=20 Participants premedicated 1-2 hours before anesthesia	Placebo n=20 Participants premedicated 1-2 hours before anesthesia
Change in VAS Anxiety Score Relative to Baseline After Premedication	0.35 Centimeter Standard Deviation 0.8	0.70 Centimeter Standard Deviation 1.6	0.65 Centimeter Standard Deviation 1.2	0.25 Centimeter Standard Deviation 0.8

PRIMARY outcome

Timeframe: Changes from baseline in VAS anxiety score at 30 minutes after premedication

VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=20 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=20 Participants premedicated 1-2 hours before anesthesia	Placebo n=20 Participants premedicated 1-2 hours before anesthesia
Change in VAS Anxiety Score Relative to Baseline at 30 Minutes After Premedication	1.15 centimeter Standard Deviation 1.4	1.72 centimeter Standard Deviation 2.2	1.62 centimeter Standard Deviation 1.6	0.82 centimeter Standard Deviation 1.6

PRIMARY outcome

Timeframe: Changes from baseline in VAS anxiety score at one hour after premedication

VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=20 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=20 Participants premedicated 1-2 hours before anesthesia	Placebo n=20 Participants premedicated 1-2 hours before anesthesia
Change in VAS Anxiety Score Relative to Baseline at One Hour After Premedication	1.80 Centimeter Standard Deviation 1.7	2.92 Centimeter Standard Deviation 2.3	2.35 Centimeter Standard Deviation 2.1	0.85 Centimeter Standard Deviation 1.9

SECONDARY outcome

Timeframe: Sedation score at 1 hour after the premedication

Sedation level was assessed with a 5 point scale (0=alert, 1=arouses to voice, 2=arouses with gentle tactile stimulation, 3=arouses with vigorous tactile stimulation, 4=lack of responsiveness). Minimum score is 0 and Maximum is 4. The lesser the score, the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=20 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=20 Participants premedicated 1-2 hours before anesthesia	Placebo n=20 Participants premedicated 1-2 hours before anesthesia
Sedation Score at One Hour After Premedication	0.5 units on a scale Interval 0.0 to 1.0	1 units on a scale Interval 1.0 to 2.75	1 units on a scale Interval 0.0 to 1.75	0 units on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: Orientation score at one hour after premedication

Orientation was assessed with a 3 point scale (0=none, 1=orientation in either time or place, 2=orientation in both). Minimum score is 0 and maximum is 2. The lesser the score, the lesser the effect on patients cognition and the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=20 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=20 Participants premedicated 1-2 hours before anesthesia	Placebo n=20 Participants premedicated 1-2 hours before anesthesia
Orientation Score	2 units on a scale Interval 2.0 to 2.0	2 units on a scale Interval 2.0 to 2.0	2 units on a scale Interval 2.0 to 2.0	2 units on a scale Interval 2.0 to 2.0

SECONDARY outcome

Timeframe: 24 hour after surgery

Number of patients who recalled or recognized the picture number five shown one hour after premedication. The more the number of patients with intact memory, the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=19 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=18 Participants premedicated 1-2 hours before anesthesia	Placebo n=18 Participants premedicated 1-2 hours before anesthesia
Number of Patients With Intact Memory	13 Participants	4 Participants	5 Participants	14 Participants

SECONDARY outcome

Timeframe: 1 - 2 hour after premedication

Dose of propofol needed for loss of response to verbal command was noted at the time of induction of general anesthesia. The lesser the propofol needed for the loss of response to verbal command, the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=19 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=18 Participants premedicated 1-2 hours before anesthesia	Placebo n=18 Participants premedicated 1-2 hours before anesthesia
Amount of Propofol Consumption	79.2 mg Standard Deviation 4	65.5 mg Standard Deviation 21	59.0 mg Standard Deviation 21	75.8 mg Standard Deviation 25

SECONDARY outcome

Timeframe: 24 hour after surgery

Patients were asked whether they recalled the event of being transferred to the operating room before anaesthesia. The lesser the number of patients with amnesia, the better the outcome.

Outcome measures

Outcome measures
Measure	Melatonin n=20 Participants premedicated 1-2 hour before anesthesia	Melatonin and Alprazolam n=19 Participants premedicated 1-2 hrs before anesthesia	Alprazolam n=18 Participants premedicated 1-2 hours before anesthesia	Placebo n=18 Participants premedicated 1-2 hours before anesthesia
Number of Patients With Loss of Memory for Being Transferred to Operating Room.	1 Participants	5 Participants	4 Participants	0 Participants

Adverse Events

Melatonin

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Melatonin and Alprazolam

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Alprazolam

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Melatonin n=20 participants at risk premedication 1-2 hour prior to anesthesia	Melatonin and Alprazolam n=19 participants at risk premedicated 1-2 hrs prior to anesthesia	Alprazolam n=18 participants at risk premedication 1-2 hr prior to anesthesia	Placebo n=18 participants at risk premedication 1-2 hr prior to anesthesia
Nervous system disorders Dizziness	25.0% 5/20 • Number of events 7 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	15.8% 3/19 • Number of events 5 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	11.1% 2/18 • Number of events 4 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	22.2% 4/18 • Number of events 5 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.
General disorders Restlessness	30.0% 6/20 • Number of events 6 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	36.8% 7/19 • Number of events 7 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	50.0% 9/18 • Number of events 9 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	44.4% 8/18 • Number of events 8 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.
Nervous system disorders Headache	20.0% 4/20 • Number of events 4 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	21.1% 4/19 • Number of events 4 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	16.7% 3/18 • Number of events 3 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	27.8% 5/18 • Number of events 5 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.
Gastrointestinal disorders Nausea and Vomiting	30.0% 6/20 • Number of events 8 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	36.8% 7/19 • Number of events 10 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	44.4% 8/18 • Number of events 11 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.	50.0% 9/18 • Number of events 12 • 24 hours after premedication Incidence of nausea and vomiting were recorded. Vitals (Blood Pressure, Heart Rate, Respiratory rate and Temperature) were assessed every 6 hours.

Additional Information

Dr Krishna Pokharel

B. P. Koirala Institute of Health Sciences

Phone: 0977-9841986321

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place