Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone
| Tracking Information | |||||||||
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| First Received Date ICMJE | November 10, 2011 | ||||||||
| Last Updated Date | December 6, 2011 | ||||||||
| Start Date ICMJE | October 2011 | ||||||||
| Estimated Primary Completion Date | December 2011 (final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
change in VAS anxiety score from baseline [ Time Frame: changes from baseline in VAS anxiety score at 15 minutes, 30 minutes and 1 hour after premedication ] [ Designated as safety issue: No ] The extremes of the VAS anxiety scale will be marked as 'no anxiety' at the 0 end and 'anxiety as bad as ever can be' at the 10 cm end. |
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | Complete list of historical versions of study NCT01486615 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Outcome Measures ICMJE | |||||||||
| Original Other Outcome Measures ICMJE | |||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone | ||||||||
| Official Title ICMJE | Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone: a Randomized, Double Blind Placebo Controlled Study | ||||||||
| 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. |
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| Detailed Description | Review of literature: Benzodiazepines are among the most popular drugs used for preoperative medication to produce anxiolysis, amnesia, and sedation. However, they negatively influence sleep quality by decreasing the duration of REM sleep and slow wave sleep. Alprazolam is more anxioselective than the more commonly used ones like midazolam, lorazepam and diazepam.Melatonin (N-acetyl-5-methoxytryptamine) is an emerging premedicant as it possesses anxiolytic and sedative properties without impairing cognitive or psychomotor skills.5 Moreover, it has an excellent safety profile. We designed this prospective randomized double blind placebo controlled study to assess whether addition of melatonin to alprazolam has any benefit over alprazolam, melatonin or placebo alone as a premedication agent. Rationale of the study Melatonin facilitates sleep onset and improves the quality of sleep. On the other hand, benzodiazepines suppress endogenous melatonin levels and thus paradoxically increase episodes of arousal during sleep causing restlessness and hang over effects (fatigue). Hence, the rationale of using melatonin alprazolam combination is melatonin may decrease nocturnal arousal and promote the perception of sound sleep and thus reverse this unwanted side effect of alprazolam. Melatonin does not produce amnesia and adding a benzodiazepine to it may be desirable to achieve this desirable premedication effect. Research design and methodology: After getting approval from the institutional research ethics committee and written informed consent, we will study eighty patients. With the help of computer generated random numbers, patients will be assigned to one of the four groups (n=20) to receive vitamin B (Group P), 0.5 mg alprazolam (Group A), 3mg melatonin (Group M) or a combination of 0.5 mg alprazolam and 3 mg melatonin (Group AM) approximately 90 minutes before surgery. In addition to the study drugs, Groups A and AM will also receive vitamin B. On the preanaesthetic visit one day prior to surgery, the patients will be explained about the nature of the study and the various scales to be used. A 10 cm linear Visual Analogue Scale (VAS) as well as Nepali version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) will be used to assess their anxiety level. The extremes of the VAS anxiety scale will be marked as 'no anxiety' at the 0 end and 'anxiety as bad as ever can be' at the 10 cm end. Sedation will be 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) and orientation, with a 3 point scale (0=none, 1=orientation in either time or place, 2=orientation in both). To test for the memory, recall of 5 different simple pictures and 2 events will be assessed. Pictures to be used will be sequentially numbered on the back and their names printed on the front. Approximately 2 hours prior to surgery, each patient will be taken to a quiet room. Non invasive blood pressure, heart rate, respiratory rate and SpO2 will be monitored. Then picture 1 (cup on a plate) and 2 (fruits) will be shown at 10 min before and just prior to the drug administration respectively. Patients will be asked to take the study medication orally with 15 ml of plain water according to the group assignment by an investigator not involved in the patient management and data collection thereafter. Then anxiety, sedation and orientation will be assessed at 15 min, 30 min and 1 hour after the drug administration. At these time points pictures 3 (bird), 4 (hare) and 5 (car) will also be shown respectively. In the operating room, intravenous access will be secured and pethidine 1 mg/kg administered. Then intravenous lidocaine 20 mg bolus will be administered followed by propofol with infusion pump at 100 ml per hour till responses to verbal command and eyelash reflex are lost. Vecuronium 0.1 mg/kg and isoflurane in oxygen will be administered to maintain the adequate depth of anaesthesia. After intubation, ventilation will be adjusted to maintain normocapnia. Incremental doses of pethidine and vecuronium will be administered as needed on the discretion of the investigator blinded to the patient's group assignment. No other analgesics will be administered. After completion of surgery, intravenous neostigmine 50 microgram/kg and glycopyrrolate 10 microgram/kg will be given to reverse muscle paralysis. Anaesthesia time (induction to emergence) will be noted. In the recovery room, patients will receive the standard postoperative care; including oxygen administration via face mask 6 L/min and monitoring of heart rate, respiratory rate, non invasive blood pressure and SpO2. Modified Aldrete score and sedation score will be assessed at 10 min and 30 min after extubation. Also the occurrence of nausea, vomiting, dizziness, headache and restlessness will be recorded till 24 hours. Vomiting will be managed with ondansetron 4 mg intravenously. The next day, the patients will be asked if they recalled the two events; being transported to operating room and intravenous cannula being inserted. They will also be asked to have a free recall of the five pictures they were shown and the score will represent the numbers of pictures they recalled. Then the first five pictures that they were shown will be mixed with next 5 new pictures (of a horse, shoe, bicycle, elephant and tiger) and they will be asked to recognize those they had already seen. The score will represent the number of pictures correctly identified. They will also be asked whether they felt that premedication drug is required to relieve anxiety and also whether they would like to receive the same premedication drug in the future. Statistical analysis: Discrete variables will be compared on the basis of the chi-square test (two by two tables) or the Fisher exact test (small frequencies). Continuous variables will be compared using the t test for independent samples and the Mann-Whitney test. The VAS, orientation and sedation scores will be compared using repeated measures analysis of variance (ANOVA). Finally, results of the memory test, patient acceptance and incidence of adverse events will be compared using the Fisher exact test. |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase | Phase 4 | ||||||||
| Study Design ICMJE | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
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| Condition ICMJE | Anxiety | ||||||||
| Intervention ICMJE |
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| Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE | 80 | ||||||||
| Completion Date | |||||||||
| Estimated Primary Completion Date | December 2011 (final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Gender | Both | ||||||||
| Ages | 18 Years to 65 Years | ||||||||
| Accepts Healthy Volunteers | Yes | ||||||||
| Contacts ICMJE |
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| Location Countries ICMJE | Nepal | ||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT01486615 | ||||||||
| Other Study ID Numbers ICMJE | 2/18 (Acd. 796/067/068) | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| Responsible Party | Krishna Pokharel, B.P. Koirala Institute of Health Sciences | ||||||||
| Study Sponsor ICMJE | B.P. Koirala Institute of Health Sciences | ||||||||
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| Information Provided By | B.P. Koirala Institute of Health Sciences | ||||||||
| Verification Date | December 2011 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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