Quetiapine Treatment for Pediatric Delirium

NCT03572257 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 1195004
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, double-blind, randomized controlled trial to begin determining the efficacy of quetiapine as a treatment for pediatric delirium in patients admitted to the pediatric intensive care unit (PICU)

Conditions

Delirium

Outcome Measures

Primary Outcomes (1)

• Time to resolution of delirium

  Delirium symptoms will be monitored using CAPD (Cornell Assessment for Pediatric Delirium) score, collected twice a day. Time to resolution of delirium will be measured from the time of randomization to the time scores are within normal range (0-8). Number of days with abnormal CAPD scores will be compared between study groups

  Screening through Study Day 14/Hospital Discharge

Study Arms (2)

Quetiapine (0.5 mg/kg TID x 10 days)

EXPERIMENTAL

This study group will receive treatment with quetiapine after diagnosis of pediatric delirium. Group assignment will be blinded.

Drug: Quetiapine

Placebo

PLACEBO COMPARATOR

This study group will receive a placebo treatment after diagnosis of pediatric delirium. Group assignment will be blinded.

Other: Placebo

Interventions

Quetiapine DRUG

Patients randomized to the study treatment group will received quetiapine at 0.5 mg/kg, three times a day for 10 days. Doses can be increased up to a maximum of 6 mg/kg/day, in increments of 0.5 mg/kg, based on the subject's clinical delirium symptoms. PRN doses of 0.5 mg/kg can be given up to three times a day based on the clinical judgement of the subject's ICU care team.

Quetiapine (0.5 mg/kg TID x 10 days)

Placebo OTHER

Patients randomized to the placebo group will be given an equivalent volume of sterile liquid or sugar pill, based on the individual subjects dosing preference or ability. Dosing will be done on the same schedule as the quetiapine group

Placebo

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 0 - 21 years old
• PICU admission
• Positive CAPD scoring
• For developmentally normal children a CAPD score of ≥ 9
• For developmentally delayed a CAPD score of ≥ 9 and a Richmond Agitation Sedation Scale (RASS) fluctuation of at least 2 points in the last 24 hours

You may not qualify if:

• Patients under neuromuscular blockade and/or therapeutic hypothermia.
• Patients undergoing treatment of alcohol withdrawal.
• Patients unable to tolerate enteral medications
• Patients on antipsychotics
• Patients with a history of:
• hepatic encephalopathy, hepatitis
• elevated liver enzymes defined ALT or AST above normal range for age since hospitalization
• baseline QTc prolongation (defined as greater than 97th percentile for age or greater than 20% increase from baseline or previous QTc)
• major depressive disorder or bipolar disorder, and movement disorder.
• Patients who are pregnant
• Non-English and non-Spanish speaking subjects and/or parent/guardian

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (23)

• Traube C, Silver G, Reeder RW, Doyle H, Hegel E, Wolfe HA, Schneller C, Chung MG, Dervan LA, DiGennaro JL, Buttram SD, Kudchadkar SR, Madden K, Hartman ME, deAlmeida ML, Walson K, Ista E, Baarslag MA, Salonia R, Beca J, Long D, Kawai Y, Cheifetz IM, Gelvez J, Truemper EJ, Smith RL, Peters ME, O'Meara AM, Murphy S, Bokhary A, Greenwald BM, Bell MJ. Delirium in Critically Ill Children: An International Point Prevalence Study. Crit Care Med. 2017 Apr;45(4):584-590. doi: 10.1097/CCM.0000000000002250.

  PMID: 28079605 BACKGROUND

• Traube C, Silver G, Gerber LM, Kaur S, Mauer EA, Kerson A, Joyce C, Greenwald BM. Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium. Crit Care Med. 2017 May;45(5):891-898. doi: 10.1097/CCM.0000000000002324.

  PMID: 28288026 BACKGROUND

• Traube C, Greenwald BM. "The Times They Are A-Changin": Universal Delirium Screening in Pediatric Critical Care. Pediatr Crit Care Med. 2017 Jun;18(6):594-595. doi: 10.1097/PCC.0000000000001142. No abstract available.

  PMID: 28574907 BACKGROUND

• Schieveld JN, Strik JJ. Pediatric Delirium: A Worldwide PICU Problem. Crit Care Med. 2017 Apr;45(4):746-747. doi: 10.1097/CCM.0000000000002275. No abstract available.

  PMID: 28291099 BACKGROUND

• Patel AK, Biagas KV, Clarke EC, Gerber LM, Mauer E, Silver G, Chai P, Corda R, Traube C. Delirium in Children After Cardiac Bypass Surgery. Pediatr Crit Care Med. 2017 Feb;18(2):165-171. doi: 10.1097/PCC.0000000000001032.

  PMID: 27977539 BACKGROUND

• Meyburg J, Dill ML, Traube C, Silver G, von Haken R. Patterns of Postoperative Delirium in Children. Pediatr Crit Care Med. 2017 Feb;18(2):128-133. doi: 10.1097/PCC.0000000000000993.

  PMID: 27776085 BACKGROUND

• Leroy PL, Schieveld JN. Mind the Heart: Delirium in Children Following Cardiac Surgery for Congenital Heart Disease. Pediatr Crit Care Med. 2017 Feb;18(2):196-198. doi: 10.1097/PCC.0000000000001038. No abstract available.

  PMID: 28157798 BACKGROUND

• Traube C, Mauer EA, Gerber LM, Kaur S, Joyce C, Kerson A, Carlo C, Notterman D, Worgall S, Silver G, Greenwald BM. Cost Associated With Pediatric Delirium in the ICU. Crit Care Med. 2016 Dec;44(12):e1175-e1179. doi: 10.1097/CCM.0000000000002004.

  PMID: 27518377 BACKGROUND

• Smith HA, Gangopadhyay M, Goben CM, Jacobowski NL, Chestnut MH, Savage S, Rutherford MT, Denton D, Thompson JL, Chandrasekhar R, Acton M, Newman J, Noori HP, Terrell MK, Williams SR, Griffith K, Cooper TJ, Ely EW, Fuchs DC, Pandharipande PP. The Preschool Confusion Assessment Method for the ICU: Valid and Reliable Delirium Monitoring for Critically Ill Infants and Children. Crit Care Med. 2016 Mar;44(3):592-600. doi: 10.1097/CCM.0000000000001428.

  PMID: 26565631 BACKGROUND

• Porter S, Holly C, Echevarria M. Infants with Delirium: A Primer on Prevention, Recognition, and Management. Pediatr Nurs. 2016 Sep-Oct;42(5):223-9.

  PMID: 29406640 BACKGROUND

• Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013 Dec;21(12):1190-222. doi: 10.1016/j.jagp.2013.09.005.

  PMID: 24206937 BACKGROUND

• Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72.

  PMID: 23269131 BACKGROUND

• Kishi T, Hirota T, Matsunaga S, Iwata N. Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2016 Jul;87(7):767-74. doi: 10.1136/jnnp-2015-311049. Epub 2015 Sep 4.

  PMID: 26341326 BACKGROUND

• Bathula M, Gonzales JP. The pharmacologic treatment of intensive care unit delirium: a systematic review. Ann Pharmacother. 2013 Sep;47(9):1168-74. doi: 10.1177/1060028013500466.

  PMID: 24259732 BACKGROUND

• Boettger S, Friedlander M, Breitbart W, Passik S. Aripiprazole and haloperidol in the treatment of delirium. Aust N Z J Psychiatry. 2011 Jun;45(6):477-82. doi: 10.3109/00048674.2011.543411.

  PMID: 21563866 BACKGROUND

• Banerjee A, Girard TD, Pandharipande P. The complex interplay between delirium, sedation, and early mobility during critical illness: applications in the trauma unit. Curr Opin Anaesthesiol. 2011 Apr;24(2):195-201. doi: 10.1097/ACO.0b013e3283445382.

  PMID: 21386669 BACKGROUND

• Martin J, Heymann A, Basell K, Baron R, Biniek R, Burkle H, Dall P, Dictus C, Eggers V, Eichler I, Engelmann L, Garten L, Hartl W, Haase U, Huth R, Kessler P, Kleinschmidt S, Koppert W, Kretz FJ, Laubenthal H, Marggraf G, Meiser A, Neugebauer E, Neuhaus U, Putensen C, Quintel M, Reske A, Roth B, Scholz J, Schroder S, Schreiter D, Schuttler J, Schwarzmann G, Stingele R, Tonner P, Trankle P, Treede RD, Trupkovic T, Tryba M, Wappler F, Waydhas C, Spies C. Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version. Ger Med Sci. 2010 Feb 2;8:Doc02. doi: 10.3205/000091.

  PMID: 20200655 BACKGROUND

• Straker DA, Shapiro PA, Muskin PR. Aripiprazole in the treatment of delirium. Psychosomatics. 2006 Sep-Oct;47(5):385-91. doi: 10.1176/appi.psy.47.5.385.

  PMID: 16959926 BACKGROUND

• Boettger S, Breitbart W. Atypical antipsychotics in the management of delirium: a review of the empirical literature. Palliat Support Care. 2005 Sep;3(3):227-37. doi: 10.1017/s1478951505050352.

  PMID: 16594462 BACKGROUND

• Ely EW, Stephens RK, Jackson JC, Thomason JW, Truman B, Gordon S, Dittus RS, Bernard GR. Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals. Crit Care Med. 2004 Jan;32(1):106-12. doi: 10.1097/01.CCM.0000098033.94737.84.

  PMID: 14707567 BACKGROUND

• Harris J, Ramelet AS, van Dijk M, Pokorna P, Wielenga J, Tume L, Tibboel D, Ista E. Clinical recommendations for pain, sedation, withdrawal and delirium assessment in critically ill infants and children: an ESPNIC position statement for healthcare professionals. Intensive Care Med. 2016 Jun;42(6):972-86. doi: 10.1007/s00134-016-4344-1. Epub 2016 Apr 15.

  PMID: 27084344 BACKGROUND

• Devlin JW, Roberts RJ, Fong JJ, Skrobik Y, Riker RR, Hill NS, Robbins T, Garpestad E. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010 Feb;38(2):419-27. doi: 10.1097/CCM.0b013e3181b9e302.

  PMID: 19915454 BACKGROUND

• Joyce C, Witcher R, Herrup E, Kaur S, Mendez-Rico E, Silver G, Greenwald BM, Traube C. Evaluation of the Safety of Quetiapine in Treating Delirium in Critically Ill Children: A Retrospective Review. J Child Adolesc Psychopharmacol. 2015 Nov;25(9):666-70. doi: 10.1089/cap.2015.0093. Epub 2015 Oct 15.

  PMID: 26469214 BACKGROUND

MeSH Terms

Conditions

Delirium

Interventions

Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: June 28, 2018
• Study Start: April 15, 2019
• Primary Completion: February 27, 2020
• Study Completion: March 2, 2020
• Last Updated: April 8, 2020

Record last verified: 2020-04

Locations

US (1)