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Treatment Of Alcohol Withdrawal Syndrome: Dexmedetomidine Vs Diazepam In A Hospital O'horán

Primary Purpose

Alcohol Withdrawal Delirium

Status
Completed
Phase
Phase 4
Locations
Mexico
Study Type
Interventional
Intervention
Dexmedetomidine 0.004 MG/ML
Diazepam Injectable Solution
Sponsored by
Centro Medico Nacional La Raza, IMSS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Withdrawal Delirium focused on measuring Dexmedetomidine, Diazepam, Alcohol dependence, Alcohol withdrawal syndrome, Benzodiacepines

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients who received dexmedetomidine during their Emergency stay
  • Patients who received diazepam during their Emergency stay
  • CIE-10 codes consistent with alcohol withdrawal during hospitalization
  • CIWA-A score >10 points

Exclusion Criteria:

  • comorbid disease, including several with CNS trauma or cerebrovascular accidents, one with end-stage metastatic carcinoma, and one patient with severe sepsis.

Sites / Locations

  • Nayely Garcia Mendez

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Active Comparator

Arm Label

Dexmedetomidine

Diazepam

Arm Description

Dexmedetomidine. Dexmedetomidine use 400 mcg in 100 cc 0.9% physiological solution in continuous infusion starting at a dose of 0.2 mcg / kg / hr titrating until reaching a decrease in the adrenergic response, with a maximum dose of 0.7 mcg / kg / hr7. Dosage form: DEX 0.2-0.7 mcg/Kg/min.

Dosage form: Diazepam 5-10 mg IV, steps until a maximum dose of 120 mg diazepam

Outcomes

Primary Outcome Measures

Average Alcohol Withdrawal Scoring
Total Score = 0 - 9: absent or minimal withdrawal 10 - 19: mild to moderate withdrawal more than 20: severe withdrawal
Average Diazepam Received (mg)
Dosis total: Diacepam 5-20 mg IV
Average Dexmedetomidine Received (mg)
Infusión: DEX 0.2-0.7 mcg/Kg/min
heart rate average
mean values per 24 hours period for each patient
Systolic blood pressure average
mean values per 24 hours period for each patient

Secondary Outcome Measures

days of hospital stay
Duration in days of hospital stay

Full Information

First Posted
March 12, 2019
Last Updated
March 14, 2019
Sponsor
Centro Medico Nacional La Raza, IMSS
Collaborators
Universidad de La Frontera
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1. Study Identification

Unique Protocol Identification Number
NCT03877120
Brief Title
Treatment Of Alcohol Withdrawal Syndrome: Dexmedetomidine Vs Diazepam In A Hospital O'horán
Official Title
Treatment Of Alcohol Withdrawal Syndrome: Dexmedetomidine Vs Diazepam In A Hospital O'horán
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
February 28, 2018 (Actual)
Study Completion Date
August 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centro Medico Nacional La Raza, IMSS
Collaborators
Universidad de La Frontera

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The cessation of alcohol consumption of people suffering from alcohol abuse frequently leads to the development of an alcohol withdrawal syndrome (AWS). The ethylic suppression syndrome is defined as the appearance of two or more data of autonomic hyperactivity, nausea, hallucinations and seizures associated with the cessation of alcohol consumption. For its evaluation, the CIWA-Ar scale is used, which guides the treatment based on benzodiazepines but with many adverse effects, so sedatives have been tried, among them dexmedetomidine, an alpha-agonist with action in the locus caeruleus, with variable results. Objectives: The investigators aimed to compare the DEX vs. Diazepam, for moderate disease, applying the CIWA-Ar scale, in participants with severe to moderate AWS. Methodology: 40 participants with CIWA-Ar greater than 10 points, the investigators are collected and randomized into two groups: one under treatment with diazepam (Group Diazepam) and another with dexmedetomidine (Group Dexmedetomidine), until the CIWA-Ar was reduced to less than 10, and adverse effects the investigators also reported. The analysis was done with student t. Results: The average duration of treatment with diazepam was 5.5 days (IC 95 = 6.6-3.8), the average duration of treatment with dexmedetomidine was 3.1 days (95% CI = 4.5-1.7), with a significant difference ( p = 0.0016). In the group with diazepam 60% presented adverse effects and in the group with dexmedetomidine 25% presented them, with a significant difference (p = 0.04). Conclusion: dexmedetomidine was superior to diazepam for the treatment of moderate-severe alcohol withdrawal with fewer adverse effects. KEY WORDS: Alcohol dependence · Alcohol withdrawal syndrome · Dexmedetomidine · Diazepam · Benzodiazepines
Detailed Description
Alcohol withdrawal syndrome AWS (Alcohol Withdrawal Syndrome), is defined as the appearance of two or more data of autonomic hyperactivity, nausea, hallucinations and seizures associated with cessation of alcohol consumption. For its evaluation, the CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol) scale is used, which guides the treatment based on benzodiazepines but a disadvantage is the related adverse effects, for which other pharmacological strategies of sedation have been tried, among them Dexmedetomidine (DEX). OBJECTIVES: The investigators aimed to compare the DEX vs. Diazepam, for moderate disease, applying the CIWA-Ar scale, in participants with severe to moderate AWS (Alcohol Withdrawal Syndrome). MATERIALS: Prior authorization from the ethics committee of O'Horán Hospital, Yucatán, Mexico. No. Registration CEI-011-1-17, and signature of informed consent. A randomized clinical trial was carried out in the Adult Emergencies service during the period July 2017-July 2018. Forty participants with CIWA-Ar greater than 10 points participated. The administration of: A) Diazepam 5-20 mg IV. B) DEX 0.2-0.7 mcg / Kg / min., until the CIWA-Ar scale decreases to <10. The investigators are excluded minor patients, mild CIWA-Ar category, previous medication, participants with severe cranial encephalic trauma (TBI) or mechanical ventilation requirement, with chronic liver failure category C in the Child-Turcotte-Pugh classification. RESULTS The CIWA Ar scale average for admission was 23 points, the lowest of 10 points and the highest of 38 points. The average number of days consuming alcohol prior to hospital admission was 131.9, with the highest average in the group that used dexmedetomidine; the average number of days after having suspended the intake until hospital admission was 1.7 days, being slightly higher in the group that used diazepam; the shortest time was 6 hours and the longest of a week without being related to the CIWA Ar score. The average duration of treatment with diazepam was 5.5 days (IC 95 = 6.6-3.8), The average duration of treatment with dexmedetomidine was 3.1 days (95% CI = 4.5-1.7) After applying t student a significant difference was found in the number of days in favor of dexmedetomidine (p = 0.0016) CONCLUSIONS The investigators found that DEX at conventional doses, for the treatment of moderate-severe alcohol withdrawal in terms of reducing the CIWA-Ar scale, in fewer days and with fewer adverse effects and complications. REFERENCES: Anderson P, Lars M, Gauden G. Alchol in the Europen Union. Consume, harm and policy approaches. Edit. WHO. 2012 Nota descriptiva N° 349: Alcohol. Organización Mundial de la Salud. 2015. Encuesta Nacional de Adicciones 2011: Reporte de Alcohol. Medina-Mora ME, Villatoro-Velázquez JA, Fleiz-Bautista C, et. Al. México: INPRFM; 2012. Longo D, Fauci A, Kasper E, et al. Harrison: Principios de Medicina Interna. 18ª ed. McGraw-Hill. México. 2012. Diagnostic and statistical manual of mental disorders. 5th edition. Washington, DC: American Psychiatric Association; 2013. 947 pp. Carson L, Kumar N, Wong-Mckinstry. Alcohol Withdrawal Syndrome. Critical Care. 2012. Jawa R, Stothert J, Shostrom V, et al. Alcohol Withdrawal Syndrome in admitted trauma patients. The American Journal of Surgery (2014)208: 781-787 Sullivan J, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989. 84(11):1353-7. Waye C, Wong M, Lee S. Implementation of a CIWA Ar Alcohol Withdrawal protocol in a Veterans Hospital. South Med Jour. 2015. 108(1):23-8. Ramírez D, Sánchez G. Capacidad diagnóstica de las escalas de Cushman y AWS para supresión etílica. Med Int de Mex. 2013. 29(1): 26-31 Miller W, McCurdy L. A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of the acute alcohol withdrawal syndrome. Clin Ther 1984. 6(3):364-71. Henrey G, Dery R, Bandes R. A prospective randomized trial of phenobarbital vs benzodiazepines for acute alcohol withdrawal. Am Jour Eme Med. 2011. 382-85. Hughes D, VanWert E, LePori L. Propofol for benzodiazepine-refractory alcohol withdrawal in a non-mechanically ventilated patient. Am Jour Eme Med. 2014. 112.e3-e4. Wong A, et al. Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal. J Crit Care. 2014. Samuels E, Szabadi E. Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation. Curr Neuropharmacol. 2008; 6(3): 235-53. Rovasalo A, Tohmo H, Aantaa R, Kettunen E, Palojoki R: Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a case report. Gen Hosp Psychiatr 2006, 28:362-363. Rayner et al. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal. Annasl of intensive care. 2012. 2:12 VanderWeid L, Foster C, McLaren R. Evaluation of early dexmedetomidine addition to the standard of care for severe alcohol withdrawal in the ICU: A retrospective controlled cohort study. Jour Int Care Med. 2014. 1-7. Frazee E, Personett H, Leung J, et al. Influence of dexmedetomidine therapy on the management of severe alcohol withdrawal síndrome in critically ill patients. Jour Crit Care. 2014. 198-302. Crispo A, Daley M, Pepin J. Comparison of clinical outcomes in nonintubated patients with severe alcohol withdrawal síndrome treated with continuous-infusion sedatives: dexmedetomidine versus benzodiazepines. Pharm. 2014. 910-17. Pita S. Determinación del tamaño muestreal. Cad Aten Prim. 1996. 138-44. Farmacología Básica y clínica. P Lorenzo, A Moreno, Lizasoain, et al. 18ª ed. Editorial Panamericana. España. 2010.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Withdrawal Delirium
Keywords
Dexmedetomidine, Diazepam, Alcohol dependence, Alcohol withdrawal syndrome, Benzodiacepines

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Clinical Trials To compare Diazepam 5-20 mg IV or Dexmedetomidine 0.2-0.7 mcg / Kg / min., In monotherapy until the CIWA-Ar decreases to <10.
Masking
Participant
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dexmedetomidine
Arm Type
Sham Comparator
Arm Description
Dexmedetomidine. Dexmedetomidine use 400 mcg in 100 cc 0.9% physiological solution in continuous infusion starting at a dose of 0.2 mcg / kg / hr titrating until reaching a decrease in the adrenergic response, with a maximum dose of 0.7 mcg / kg / hr7. Dosage form: DEX 0.2-0.7 mcg/Kg/min.
Arm Title
Diazepam
Arm Type
Active Comparator
Arm Description
Dosage form: Diazepam 5-10 mg IV, steps until a maximum dose of 120 mg diazepam
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine 0.004 MG/ML
Intervention Description
Experimental studies and single case reports suggest the α2-agonist dexmedetomidine is effective in managing the autonomic symptoms seen with alcohol withdrawal.
Intervention Type
Drug
Intervention Name(s)
Diazepam Injectable Solution
Intervention Description
diazepam start with 5-20 mg IV as a dose response, steps until a maximum dose of 120 mg diazepam.
Primary Outcome Measure Information:
Title
Average Alcohol Withdrawal Scoring
Description
Total Score = 0 - 9: absent or minimal withdrawal 10 - 19: mild to moderate withdrawal more than 20: severe withdrawal
Time Frame
dosing, total dose per 24 hours period for each patient, limited to 10 days
Title
Average Diazepam Received (mg)
Description
Dosis total: Diacepam 5-20 mg IV
Time Frame
Limited to 10 days
Title
Average Dexmedetomidine Received (mg)
Description
Infusión: DEX 0.2-0.7 mcg/Kg/min
Time Frame
dosing, total dose per 24 hours period for each patient, limited to 10 days
Title
heart rate average
Description
mean values per 24 hours period for each patient
Time Frame
24 hours
Title
Systolic blood pressure average
Description
mean values per 24 hours period for each patient
Time Frame
24hours
Secondary Outcome Measure Information:
Title
days of hospital stay
Description
Duration in days of hospital stay
Time Frame
24 hours limited to 10 days

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who received dexmedetomidine during their Emergency stay Patients who received diazepam during their Emergency stay CIE-10 codes consistent with alcohol withdrawal during hospitalization CIWA-A score >10 points Exclusion Criteria: comorbid disease, including several with CNS trauma or cerebrovascular accidents, one with end-stage metastatic carcinoma, and one patient with severe sepsis.
Facility Information:
Facility Name
Nayely Garcia Mendez
City
Ciudad de Mexico
ZIP/Postal Code
4780000
Country
Mexico

12. IPD Sharing Statement

Citations:
PubMed Identifier
8701843
Citation
Yost DA. Alcohol withdrawal syndrome. Am Fam Physician. 1996 Aug;54(2):657-64, 669. Erratum In: Am Fam Physician 1996 Dec;54(8):2377.
Results Reference
result
PubMed Identifier
33423824
Citation
Garcia-Mendez N, Briceno-Santana M, Totomoch-Serra A, Manterola C, Otzen T, Valdez PS, Campos-Duran R, Reyna GC. The hemodynamic effects of diazepam versus dexmedetomidine in the treatment of alcohol withdrawal syndrome: A randomized clinical trial. Med Clin (Barc). 2021 Dec 24;157(12):561-568. doi: 10.1016/j.medcli.2020.09.023. Epub 2021 Jan 8. English, Spanish.
Results Reference
derived

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Treatment Of Alcohol Withdrawal Syndrome: Dexmedetomidine Vs Diazepam In A Hospital O'horán

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