Impact of Gabapentin on Slow Wave Sleep in Adult Critically Ill Patient (GASWAC)

Impact of Gabapentin on Slow Wave Sleep in Adult Critically Ill Patient.

The investigators proposed that gabapentin will increase slow-wave sleep in adult critically ill patients. Increasing slow-wave sleep will improve the patients' outcomes (shortening ICU length of stay, improving ventilator free days, increasing delirium free days) in critically ill patients, a university hospital, Thailand.

Study Overview

• Status: Completed
• Conditions: Sleep Deprivation; Critically Ill
• Intervention / Treatment: Drug: Gabapentin

Detailed Description

Up to 61% of critically ill patients have sleep deprivation in ICU. Sleep deprivation can cause delirium and lead to prolonged ICU length of stay and mechanical ventilator days. However, pharmacologic interventions to improve sleep quality and prevent sleep deprivation are poorly tested for efficacy and safety in ICU patients. There were reports of gabapentin increasing slow-wave sleep in healthy populations and insomnia patients with insignificant adverse events. Therefore, gabapentin might increase slow-wave sleep resulting in improving clinical outcomes in adult critically ill patients. The objectives of the study were to evaluate the efficacy, especially on slow-wave sleep, and safety of gabapentin in adult critically ill patients admitted to ICUs at Ramathibodi Hospital, a university hospital, Thailand.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Ratchathewi, Bangkok, Thailand, 10400
      • Ramathibodi Hospital, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults (18 years and older)
• Patients admitted to ICU not more than 24 hours at the time of randomization

Exclusion Criteria:

• Patients admitted to ICU less than 72 hours
• Patients receiving gabapentin within 14 days prior to randomization
• Patients receiving restorative drug (trazodone, mirtazapine, olanzapine, agomelatine, and pregabalin) within 7 days prior to randomization
• Patients having contraindications to gabapentin
• Patients receiving high dose vasopressors more than 1 hour during ICU admissions
• Patients presenting with severe respiratory failure (PF ratio < 100)
• Patients presenting with RASS < -2 at the time of randomization
• Patients having target RASS of <-2 during ICU admissions
• Terminal ill patients
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gabapentin; Start gabapentin 100 mg at 9.00 PM on the second night of ICU admission and titrate gabapentin dose as needed. Maximum gabapentin dose in this study is 300 mg/day.	Drug: Gabapentin; Gabapentin 100-300 mg is given to the intervention group; Other Names: Gabapentin group
No Intervention: Standard care; Not receiving gabapentin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slow-wave sleep	Slow-wave sleep period or deep sleep period	at least 3 consecutive days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU free days	Days alive and not stay in ICU	During ICU stay or death or a maximum of 28 days
Mechanical ventilator free days	Day alive and free of mechanical ventilator	During ICU stay or death or a maximum of 28 days
All-cause hospital mortality	Rates of all-cause mortality during hospital stay	During hospital stay or death or a maximum of 90 days
Hospital free days	Days alive and not stay in hospital	During hospital stay or death or a maximum of 90 days
Incidence of self-extubation	Number of patients who had self-extubation during ICU stay	During ICU stay or death or a maximum of 28 days
Incidence of sleep deprivation	Times per patient-days of sleep deprivation during ICU stay	During ICU stay or death or a maximum of 28 days
Delirium free day	Days alive and not having delirium	During ICU stay or death or a maximum of 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
IGF-1	IGF-1 level	At day 0, 1, 3, and 5 after randomization

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Study Director: Yuda Sutherasan, MD, Ramathibodi Hospital, Mahidol University; Principal Investigator: Kanyarat Susantitapong, B.Sc.(Pharm), Mahidol University; Study Director: Pitchaya Dilokpattanamongkol, BCPS, BCCCP, BCP, Mahidol University; Study Chair: Chuthamanee Suthisisang, Ph.D., Mahidol University; Study Chair: Viratch Tangsujaritvijit, Ph.D., Piyavate Hospital

Publications and helpful links

General Publications

• Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.
• Arttawejkul P, Reutrakul S, Muntham D, Chirakalwasan N. Effect of Nighttime Earplugs and Eye Masks on Sleep Quality in Intensive Care Unit Patients. Indian J Crit Care Med. 2020 Jan;24(1):6-10. doi: 10.5005/jp-journals-10071-23321.
• Carrera-Hernandez L, Aizpitarte-Pejenaute E, Zugazagoitia-Ciarrusta N, Goni-Viguria R. Patients' perceptions of sleep in a Critical Care Unit. Enferm Intensiva (Engl Ed). 2018 Apr-Jun;29(2):53-63. doi: 10.1016/j.enfi.2018.01.002. Epub 2018 Mar 28. English, Spanish.
• Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, Mascha E, Dinner D, Morris HH. Gabapentin increases slow-wave sleep in normal adults. Epilepsia. 2002 Dec;43(12):1493-7. doi: 10.1046/j.1528-1157.2002.21002.x.
• Liu GJ, Karim MR, Xu LL, Wang SL, Yang C, Ding L, Wang YF. Efficacy and Tolerability of Gabapentin in Adults with Sleep Disturbance in Medical Illness: A Systematic Review and Meta-analysis. Front Neurol. 2017 Jul 14;8:316. doi: 10.3389/fneur.2017.00316. eCollection 2017.
• Rosenberg RP, Hull SG, Lankford DA, Mayleben DW, Seiden DJ, Furey SA, Jayawardena S, Roth T. A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med. 2014 Oct 15;10(10):1093-100. doi: 10.5664/jcsm.4108.
• Lo HS, Yang CM, Lo HG, Lee CY, Ting H, Tzang BS. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol. 2010 Mar-Apr;33(2):84-90. doi: 10.1097/WNF.0b013e3181cda242.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): June 25, 2022
• Study Completion (Actual): July 31, 2022

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: critically ill patients; sleep deprivation; gabapentin; slow-wave sleep
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Disease Attributes; Critical Illness; Sleep Deprivation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: MURA2021/170

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No