Phenobarbital vs Ativan for Alcohol Withdrawal in the Intensive Care Unit

Alcohol Withdrawal Clinical Trial

— PARTI  

Official title:

Phenobarbital Versus Ativan for Refractory Alcohol Withdrawal Treatment in the Intensive Care Unit

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04156464
• Other study ID #: 1499413
• Status: Recruiting
• Phase: Phase 4
• Start date: July 6, 2020
• Est. completion date: March 1, 2022

Study information

• Verified date: October 2020
• Source: OSF Healthcare System
• Contact: Rachael M Davis, MD
• Phone: 309-655-7257
• Email: rachael.m.davis[@]osfhealthcare.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Our aim is to compare outcomes of patients with benzodiazepine-refractory alcohol withdrawal syndrome who are treated with either a phenobarbital-based or a lorazepam based protocol.

Description:

• This study is a prospective, open-label, randomized, controlled trial.

• The electronic medical record will be used to identify patients who have a diagnosis of alcohol withdrawal or are receiving alcohol withdrawal. Subjects who are anticipated to meet inclusion criteria will be pre-consented for the study using an informed consent process. see informed consent form.

• Subjects will not be enrolled and randomized until they have met inclusion criteria.

• If a patient meets criteria, but is deemed non-decisional or unable to give consent, the patient's medical decision maker will undergo the informed consent process.

• After enrollment, participants will be randomized to either the control group (lorazepam-based therapy) or the study group (phenobarbital-based therapy)

• Personnel unassociated with patient screening, enrollment, or follow up will create the allocation sequence and will use a random, computerized number generator. The allocation sequence will then be transferred to sequentially numbered, opaque envelopes for purposes of allocation concealment. These sequentially numbered envelopes, which are blinded to clinical trial coordinators/physicians, will be handed out in order as patients are enrolled. Clinical trial coordinators/physicians will verify treatment eligibility and informed consent before opening the envelope to obtain the treatment assignment.

• The study group will be placed on the phenobarbital-based protocol as described below in procedures. The control group will be placed on the lorazepam-based protocol, also listed below in procedures.

• All medications in the study are FDA approved. No investigational medicines will be used.

• Data will be collected on each participant as noted below in measurements.

• The data will be analyzed and published as noted above in the statistical analysis plan and data use and management section.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 142
• Est. completion date: March 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients will be eligible for randomization if he/she has met one of the following three conditions:

1. has required more than 10 mg of lorazepam within a one hour time period,

2. has required more than 30 mg of lorazepam within a four hour time period, or

3. requires admission/transfer to the intensive care unit for primarily uncontrolled alcohol withdrawal symptoms

Exclusion Criteria:

• Patients will be excluded from the study if he/she:

1. has a traumatic brain injury or other neurological condition requiring frequent neurological assessment (stroke, intracranial hemorrhage, active seizures on admission)

2. has severe hypotension requiring vasopressor support

3. is less than 18 years of age

4. is actively pregnant

5. has an allergy to either of the drugs being studied (phenobarbital or lorazepam)

6. is already intubated at the time of randomization

Related Conditions & MeSH terms

• Alcohol Withdrawal
• Alcohol Withdrawal Delirium
• Delirium

Intervention

Drug:
• Phenobarbital
Phenobarbital loading dose followed by a taper will be given to control acute alcohol withdrawal syndrome
• Lorazepam
Ativan will be given according to our institutional alcohol withdrawal protocol to control acute alcohol withdrawal syndrome

Locations

Country	Name	City	State
United States	OSF Saint Francis Medical Center	Peoria	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
OSF Healthcare System

Country where clinical trial is conducted

United States, 

References & Publications (28)

Askgaard G, Hallas J, Fink-Jensen A, Molander AC, Madsen KG, Pottegård A. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality. Drug Alcohol Depend. 2016 Apr 1;161:258-64. doi: 10.1016/j.drugalcdep.2016.02.016. Epub 2016 Feb 18. — View Citation

Crispo AL, Daley MJ, Pepin JL, Harford PH, Brown CV. Comparison of clinical outcomes in nonintubated patients with severe alcohol withdrawal syndrome treated with continuous-infusion sedatives: dexmedetomidine versus benzodiazepines. Pharmacotherapy. 2014 Sep;34(9):910-7. doi: 10.1002/phar.1448. Epub 2014 Jun 5. — View Citation

Dixit D, Endicott J, Burry L, Ramos L, Yeung SY, Devabhakthuni S, Chan C, Tobia A, Bulloch MN. Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients. Pharmacotherapy. 2016 Jul;36(7):797-822. doi: 10.1002/phar.1770. Epub 2016 Jun 30. Review. — View Citation

Duby JJ, Berry AJ, Ghayyem P, Wilson MD, Cocanour CS. Alcohol withdrawal syndrome in critically ill patients: protocolized versus nonprotocolized management. J Trauma Acute Care Surg. 2014 Dec;77(6):938-43. doi: 10.1097/TA.0000000000000352. — View Citation

Friedmann PD. Alcohol use in adults. N Engl J Med. 2013 Apr 25;368(17):1655-6. doi: 10.1056/NEJMc1302445. — View Citation

Gashlin LZ, Groth CM, Wiegand TJ, et al. Comparison of alcohol withdrawal outcomes in patients treated with benzodiazepines alone versus adjunctive phenobarbital: a retrospective cohort study. Asia Pac J Med Toxicol 2015;4:31-6.

Gold JA, Rimal B, Nolan A, Nelson LS. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens. Crit Care Med. 2007 Mar;35(3):724-30. — View Citation

Hack JB, Hoffmann RS, Nelson LS. Resistant alcohol withdrawal: does an unexpectedly large sedative requirement identify these patients early? J Med Toxicol. 2006 Jun;2(2):55-60. — View Citation

Hendey GW, Dery RA, Barnes RL, Snowden B, Mentler P. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. Am J Emerg Med. 2011 May;29(4):382-5. doi: 10.1016/j.ajem.2009.10.010. Epub 2010 Mar 25. — View Citation

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Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007 Dec 12;298(22):2644-53. — View Citation

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Rosenson J, Clements C, Simon B, Vieaux J, Graffman S, Vahidnia F, Cisse B, Lam J, Alter H. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013 Mar;44(3):592-598.e2. doi: 10.1016/j.jemermed.2012.07.056. Epub 2012 Sep 19. — View Citation

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Sarff M, Gold JA. Alcohol withdrawal syndromes in the intensive care unit. Crit Care Med. 2010 Sep;38(9 Suppl):S494-501. doi: 10.1097/CCM.0b013e3181ec5412. — View Citation

Tangmose K, Nielsen MK, Allerup P, Ulrichsen J. Linear correlation between phenobarbital dose and concentration in alcohol withdrawal patients. Dan Med Bull. 2010 Aug;57(8):A4141. — View Citation

Tidwell WP, Thomas TL, Pouliot JD, Canonico AE, Webber AJ. Treatment of Alcohol Withdrawal Syndrome: Phenobarbital vs CIWA-Ar Protocol. Am J Crit Care. 2018 Nov;27(6):454-460. doi: 10.4037/ajcc2018745. — View Citation

Wong A, Benedict NJ, Lohr BR, Pizon AF, Kane-Gill SL. Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol. Drug Alcohol Depend. 2015 Sep 1;154:296-9. doi: 10.1016/j.drugalcdep.2015.07.005. Epub 2015 Jul 16. — View Citation

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ICU length of stay	number of days in the intensive care unit	study completion, up to 18 months
Secondary	Hospital length of stay	number of days in the hospital	Study completion, up to 18 months
Secondary	30-day readmission	rate of readmission of patients within 30 days for any cause	study complettion, up to 18 months
Secondary	mortality	number of deaths	Study completion, up to 18 months
Secondary	Intubation	rate of endotracheal intubation	study completion, up to 18 months
Secondary	Hospitalization cost	Cost of index hospital stay	Study completion, up to 18 months
Secondary	Lorazepam use	total lorazepam use in mg during the entire hospital stay	Study completion, up to 18 months
Secondary	dexmedetomidine use	total dexmedetomidine used in mcg during the entire hospital stay	Study completion, up to 18 months
Secondary	propofol use	total propofol used in mg during the entire hospital stay	Study completion, up to 18 months