Cerebrolysin in Critically Ill Patients With Delirium

NCT06677502 | Enrolling By Invitation

• 2 other identifiers: CEREBDELDS352/2024
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Delirium is a severe problem in critically ill patients, and it is associated with increased morbidity, mortality, and extended stay in hospital. The pathophysiology of delirium is multifactorial and still poorly recognized. Several authors proposed different pathomechanisms of delirium. The most likely of these are a metabolic response to cerebral hypoxia/hyperoxia, oxidative stress with excessive reactive oxygen species production, neuroinflammation following general inflammatory response, disorders in neurotransmitters, especially impaired cholinergic and dopaminergic transmissions and dysregulation of tryptophan metabolisms including kynurenine and serotonin/melatonin pathways. The multifactorial pathomechanism of delirium significantly reduces targeted therapy. Due to cerebrolysin properties, it seems reasonable to conclude that this substance is effective in the prevention and treatment of delirium in critically ill patients. Cerebrolysin is commonly used in neurologic patients treated for dementia and Alzheimer's disease. It possesses antioxidative properties, which reduce the severity of post-ischaemic neuronal dysfunction and improve neuronal plasticity. It also increases acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner, improving neuronal plasticity. Additionally, cerebrolysin reduces neuroinflammation and neuronal cell apoptosis by activating toll-like receptor pathways. These properties closely correspond to the pathomechanism of delirium. Therefore, the aim of this study is to analyze the effectiveness of treatment with Cerebrolysin in critically ill patients with delirium. This study enrolls adult critically ill patients. Prior to delirium detection, the Richmond Agitation-Sedation Scale (RASS) is used to assess the level of consciousness. Patients with RASS-4 or -5 were excluded from the analysis, as these disorders of consciousness preclude the determination of the degree of delirium, which is a requisite component of the study. Delirium is detected by the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC). Additionally, the Montreal Cognitive Assessment Scale is used to detect mild cognitive impairment. The primary endpoint of this study is an analysis of the prevalence and severity of delirium symptoms. The secondary endpoint is an analysis of the duration of delirium.

Conditions

Cognitive Impairment

Keywords

delirium; critically ill; treatment; Cerebrolysin

Outcome Measures

Primary Outcomes (2)

• CAM-ICU test

  Cerebrolysin, 50 mL daily administered intravenously for seven consecutive days, reduces or alleviates the severity of delirium detected by the CAM-ICU test.

  seven days

• ICDSC test

  Cerebrolysin, 50 mL daily administered intravenously for seven consecutive days, reduces or alleviates the severity of delirium detected by the ICDSC test.

  seven days

Secondary Outcomes (1)

• MoCA test

  seven days

Study Arms (2)

Cerebrolysin arm.

EXPERIMENTAL

Patients in group CER received Cerebrolysin infusion at the dose of 50 mL solved in 0.9% NaCl for seven consecutive days, after delirium diagnose.

Drug: Cerebrolysin

Control arm.

PLACEBO COMPARATOR

Patients in group K (control) received 0.9% NaCl for seven consecutive days.

Other: Saline Solution - IV

Interventions

Cerebrolysin DRUG

Patients were randomized into two groups: CBL - patients treated with cerebrolysin at the daily dose of 50 mL, and K - control patients treated without cerebrolysin. Cerebrolysin was administrated intravenously on the day the delirium was detected and then for seven consecutive days.

Cerebrolysin arm.

Saline Solution - IV OTHER

Patients enrolled in group K received the infusion of 0.9% Saline solution at a volume of 250 mL.

Control arm.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age \> 18,
• symptoms of delirium,
• critical illness treated in Intensive Care Unit

You may not qualify if:

• pregnancy
• traumatic brain injury,
• neuroinflammatory diseases

Sponsors & Collaborators

• Medical University of Lublin: lead

Study Sites (1)

First Department of Anaesthesiology and Intensive Therapy Medical University of Lublin

Lubin, Lublin Voivodeship, 20-090, Poland

Location

Related Publications (18)

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  PMID: 37936249 RESULT

• 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 RESULT

• Landoure G, Sullivan JM, Johnson JO, Munns CH, Shi Y, Diallo O, Gibbs JR, Gaudet R, Ludlow CL, Fischbeck KH, Traynor BJ, Burnett BG, Sumner CJ. Exome sequencing identifies a novel TRPV4 mutation in a CMT2C family. Neurology. 2012 Jul 10;79(2):192-4. doi: 10.1212/WNL.0b013e31825f04b2. Epub 2012 Jun 6. No abstract available.

  PMID: 22675077 RESULT

• Flores IO, Trevino S, Diaz A. Neurotrophic fragments as therapeutic alternatives to ameliorate brain aging. Neural Regen Res. 2023 Jan;18(1):51-56. doi: 10.4103/1673-5374.331867.

  PMID: 35799508 RESULT

• Hoel H, Heggelund L, Reikvam DH, Stiksrud B, Ueland T, Michelsen AE, Otterdal K, Muller KE, Lind A, Muller F, Dudman S, Aukrust P, Dyrhol-Riise AM, Holter JC, Troseid M. Elevated markers of gut leakage and inflammasome activation in COVID-19 patients with cardiac involvement. J Intern Med. 2021 Apr;289(4):523-531. doi: 10.1111/joim.13178. Epub 2020 Oct 8.

  PMID: 32976665 RESULT

• Sharma S, Raj K, Singh S. Protective effects of cerebrolysin against chemotherapy (carmustine) induced cognitive impairment in Albino mice. Drug Chem Toxicol. 2022 Nov;45(6):2769-2779. doi: 10.1080/01480545.2021.1991195. Epub 2021 Oct 21.

  PMID: 34674598 RESULT

• Liu Z, Hu M, Lu P, Wang H, Qi Q, Xu J, Xiao Y, Fan M, Jia Y, Zhang D. Cerebrolysin alleviates cognitive deficits induced by chronic cerebral hypoperfusion by increasing the levels of plasticity-related proteins and decreasing the levels of apoptosis-related proteins in the rat hippocampus. Neurosci Lett. 2017 Jun 9;651:72-78. doi: 10.1016/j.neulet.2017.04.022. Epub 2017 Apr 27.

  PMID: 28458021 RESULT

• Kotfis K, Ely EW, Shehabi Y. Intensive care unit delirium-a decade of learning. Lancet Respir Med. 2023 Jul;11(7):584-586. doi: 10.1016/S2213-2600(23)00222-9. No abstract available.

  PMID: 37414511 RESULT

• Ottens TH, Hermes C, Page V, Oldham M, Arora R, Bienvenu OJ 3rd, van den Boogaard M, Caplan G, Devlin JW, Friedrich ME, van Gool WA, Hanison J, Hansen HC, Inouye SK, Kamholz B, Kotfis K, Maas MB, MacLullich AMJ, Marcantonio ER, Morandi A, van Munster BC, Muller-Werdan U, Negro A, Neufeld KJ, Nydahl P, Oh ES, Pandharipande P, Radtke FM, Raedt S, Rosenthal LJ, Sanders R, Spies CD, Vardy ERLC, Wijdicks EF, Slooter AJC. The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach. Delirium (Bielef). 2024;2024:10.56392/001c.90652. doi: 10.56392/001c.90652. Epub 2024 Jan 12.

  PMID: 38348284 RESULT

• Kotfis K, Maj P, Szylinska A, Pankowiak M, Reszka E, Ely EW, Marra A. The spectrum of psychological disorders in family members of patients suffering from delirium associated with critical illness: a prospective, observational study. Sci Rep. 2024 Feb 24;14(1):4562. doi: 10.1038/s41598-024-53968-3.

  PMID: 38402273 RESULT

• Dabrowski W, Siwicka-Gieroba D, Gasinska-Blotniak M, Zaid S, Jezierska M, Pakulski C, Williams Roberson S, Wesley Ely E, Kotfis K. Pathomechanisms of Non-Traumatic Acute Brain Injury in Critically Ill Patients. Medicina (Kaunas). 2020 Sep 13;56(9):469. doi: 10.3390/medicina56090469.

  PMID: 32933176 RESULT

• Cui S, Chen N, Yang M, Guo J, Zhou M, Zhu C, He L. Cerebrolysin for vascular dementia. Cochrane Database Syst Rev. 2019 Nov 11;2019(11):CD008900. doi: 10.1002/14651858.CD008900.pub3.

  PMID: 31710397 RESULT

• Seidl LF, Aigner L. Comparing the biological activity and composition of Cerebrolysin with other peptide preparations. J Med Life. 2024 Jan;17(1):24-27. doi: 10.25122/jml-2024-0129.

  PMID: 38737662 RESULT

• Ulderich Williams SC, Qaddoumi AI, Meghreblian JT, McBride ME, King SA, Elahi MA, Tuggle D, Heidel RE, Smith LM. Incidence and Risk Factors for ICU-Associated Delirium in the Alert Geriatric Trauma Population. Am Surg. 2024 Jul;90(7):1866-1871. doi: 10.1177/00031348241241707. Epub 2024 Mar 23.

  PMID: 38520278 RESULT

• Duprey MS, Devlin JW, van der Hoeven JG, Pickkers P, Briesacher BA, Saczynski JS, Griffith JL, van den Boogaard M. Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults. Crit Care Med. 2021 Aug 1;49(8):1303-1311. doi: 10.1097/CCM.0000000000004976.

  PMID: 33861548 RESULT

• Lu W, Zhu Z, Shi D, Li X, Luo J, Liao X. Cerebrolysin alleviates early brain injury after traumatic brain injury by inhibiting neuroinflammation and apoptosis via TLR signaling pathway. Acta Cir Bras. 2022 Sep 5;37(6):e370605. doi: 10.1590/acb370605. eCollection 2022.

  PMID: 36074398 RESULT

• Kotfis K, Marra A, Ely EW. ICU delirium - a diagnostic and therapeutic challenge in the intensive care unit. Anaesthesiol Intensive Ther. 2018;50(2):160-167. doi: 10.5603/AIT.a2018.0011. Epub 2018 Jun 8.

  PMID: 29882581 RESULT

• Eman G, Marsh A, Gong MN, Hope AA. Utility of Screening for Cognitive Impairment at Hospital Discharge in Adult Survivors of Critical Illness. Am J Crit Care. 2022 Jul 1;31(4):306-314. doi: 10.4037/ajcc2022447.

  PMID: 35773197 RESULT

MeSH Terms

Conditions

Cognitive Dysfunction; Delirium; Critical Illness

Interventions

cerebrolysin

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. MD, PhD

Model Details: Patients enrolled to the intervention group (CER group) receive Cerebrolysin for 7 consecutive days at a dose of 50mL daily administrated in 250 mL 0.9% NaCl. Patients enrolled the control group (K group) receive 250 mL 0.9% NaCl.

Study Record Dates

• First Submitted: September 29, 2024
• First Posted: November 6, 2024
• Study Start: January 1, 2024
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: December 31, 2024

Record last verified: 2024-12

Locations

PL (1)