Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone

NCT01486615 | Completed Phase 4 Results

• 1 other identifier: 2/18 (Acd. 796/067/068)
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Benzodiazepine, a common premedicant, suppresses endogenous melatonin levels and thus paradoxically increases episodes of arousal during sleep and thus causes restlessness and hangs over effects. Adding melatonin to it may decrease nocturnal arousal and promote the perception of sound sleep in the perioperative period. Methods: Eighty patients (ASA 1\&2) with anxiety VAS ≥ 2 posted for general anaesthesia will be randomly assigned to receive 0.5 mg alprazolam (Group A), 3 mg melatonin, a combination of 0.5 mg alprazolam and 3 mg melatonin (Group AM), or a similar looking placebo (Group P), approximately 90 minutes before surgery.

Conditions

Anxiety

Keywords

premedication; premedicants; preoperative anxiety; melatonin; alprazolam

Outcome Measures

Primary Outcomes (3)

• Change in VAS Anxiety Score Relative to Baseline 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.

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

• Change in VAS Anxiety Score Relative to Baseline 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.

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

• Change in VAS Anxiety Score Relative to Baseline 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.

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

Secondary Outcomes (5)

• Sedation Score at One Hour After Premedication

  Sedation score at 1 hour after the premedication

• Orientation Score

  Orientation score at one hour after premedication

• Number of Patients With Intact Memory

  24 hour after surgery

• Amount of Propofol Consumption

  1 - 2 hour after premedication

• Number of Patients With Loss of Memory for Being Transferred to Operating Room.

  24 hour after surgery

Study Arms (4)

Melatonin

PLACEBO COMPARATOR

Premedication with 3 mg melatonin (Meloset) tablet orally 1-2 hour prior to anesthesia

Drug: meloset (melatonin)

melatonin and alprazolam premedication

PLACEBO COMPARATOR

Premedication with 3 mg melatonin and 0.5 mg alprazolam (Stresnil) tablet orally 1-2 hrs prior to anesthesia

Drug: stresnil ( melatonin and alprazolam)

alprazolam premedication

PLACEBO COMPARATOR

Premedication with 0.5 mg alprazolam (Alprax) tablet orally 1-2 hr prior to anesthesia

Drug: (alprax) alprazolam

placebo premedication

ACTIVE COMPARATOR

Premedication with a similar looking placebo tablet orally 1-2 hr prior to anesthesia

Drug: placebo

Interventions

meloset (melatonin) DRUG

3 mg melatonin tablet 1-2 hour prior surgery

Melatonin

stresnil ( melatonin and alprazolam) DRUG

3 mg melatonin and 0.5 mg alprazolam 1-2 hr before anesthesia

melatonin and alprazolam premedication

(alprax) alprazolam DRUG

0.5 mg alprazolam

alprazolam premedication

placebo DRUG

similar looking placebo tablet

placebo premedication

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (ASA 1\&2),
• aging 18 to 65 years
• having anxiety VAS score of more than 2
• posted for general anaesthesia with estimated duration of \< 3 hours.

You may not qualify if:

• patients taking analgesics, sedatives, antiepileptics or antidepressants,
• suffering from obesity (BMI ≥ 28) or neuropsychiatric disease,
• having allergy to the study drugs

Sponsors & Collaborators

• B.P. Koirala Institute of Health Sciences: lead

Study Sites (2)

B. P. Koirala Institute of Health Sciences

Dharān, Koshi, 56700, Nepal

Location

Dr Krishna Pokharel

Dharān, Koshi, 56700, Nepal

Location

Related Publications (8)

• Naguib M, Samarkandi AH, Moniem MA, Mansour Eel-D, Alshaer AA, Al-Ayyaf HA, Fadin A, Alharby SW. The effects of melatonin premedication on propofol and thiopental induction dose-response curves: a prospective, randomized, double-blind study. Anesth Analg. 2006 Dec;103(6):1448-52. doi: 10.1213/01.ane.0000244534.24216.3a.

  PMID: 17122221 BACKGROUND

• Naguib M, Samarkandi AH. The comparative dose-response effects of melatonin and midazolam for premedication of adult patients: a double-blinded, placebo-controlled study. Anesth Analg. 2000 Aug;91(2):473-9. doi: 10.1097/00000539-200008000-00046.

  PMID: 10910871 BACKGROUND

• Naguib M, Samarkandi AH. Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. Br J Anaesth. 1999 Jun;82(6):875-80. doi: 10.1093/bja/82.6.875.

  PMID: 10562782 BACKGROUND

• De Witte JL, Alegret C, Sessler DI, Cammu G. Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam. Anesth Analg. 2002 Dec;95(6):1601-6, table of contents. doi: 10.1097/00000539-200212000-00024.

  PMID: 12456424 BACKGROUND

• Seabra ML, Bignotto M, Pinto LR Jr, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res. 2000 Nov;29(4):193-200. doi: 10.1034/j.1600-0633.2002.290401.x.

  PMID: 11068941 BACKGROUND

• Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007 Oct;23(10):2597-605. doi: 10.1185/030079907X233098.

  PMID: 17875243 BACKGROUND

• Wurtman RJ, Zhdanova I. Improvement of sleep quality by melatonin. Lancet. 1995 Dec 2;346(8988):1491. doi: 10.1016/s0140-6736(95)92509-0. No abstract available.

  PMID: 7491013 BACKGROUND

• Pokharel K, Tripathi M, Gupta PK, Bhattarai B, Khatiwada S, Subedi A. Premedication with oral alprazolam and melatonin combination: a comparison with either alone--a randomized controlled factorial trial. Biomed Res Int. 2014;2014:356964. doi: 10.1155/2014/356964. Epub 2014 Jan 12.

  PMID: 24527443 DERIVED

Related Links

• about its FDA status

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Melatonin; Azaperone; Alprazolam

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Butyrophenones; Ketones; Organic Chemicals; Benzodiazepines; Benzazepines

Limitations and Caveats

The study was not designed to measure drug plasma concentrations. We did not perform a battery of tests to evaluate psychomotor and amnesic performances. We only did an orientation score and assessed delayed visual episodic memory.

Results Point of Contact

• Title: Dr Krishna Pokharel
• Organization: B. P. Koirala Institute of Health Sciences

drkrishnapokharel@gmail.com

0977-9841986321

Study Officials

• Krishna Pokharel, MD

  B.P. Koirala Institute of Health Sciences

  PRINCIPAL INVESTIGATOR

• Balkrishna Bhattarai, MD

  B.P. Koirala Institute of Health Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 10, 2011
• First Posted: December 6, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: October 5, 2012
• Results First Posted: October 5, 2012

Record last verified: 2012-09

Locations

NE (2)