The Study of Pharmacokinetics and Pharmacodynamics of Cisatracurium

NCT03337373 | Completed Phase 4 DMC

• 1 other identifier: 06-60-07
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Pathophysiological changes influenced by multiple factors in critically ill patients, has a significant impact on pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium. In order to understand better and find an appropriate dosing regimen, the purpose of this study is to investigate the PK and PD of a loading dose cisatracurium in critically ill patients. Cisatracurium, nondepolarizing neuromuscular blocking agents (NMBAs), are commonly used in intensive care units because of a lesser effect on hemodynamic parameters and a reduction in mortality rate in ARDS patients. Loading dose recommended in clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient is 0.1-0.2 mg/kg. Then, maintenance dose of 1-3 mcg/kg/min is followed regarding indications, such as ARDS. However, this recommended loading dose might not be adequate in critically ill patients, the study in this specific population might be needed.

Conditions

Critical Illness; Respiratory Distress Syndrome, Adult; Neuromuscular Blockade; Respiratory Failure; Paralysis; ARDS, Human

Keywords

Critical care; Neuromuscular Blocking Agents; Pharmacodynamics; Pharmacokinetics; Physiological Effects of Drugs

Outcome Measures

Primary Outcomes (3)

• Total plasma concentration-time data

  Data will be collected in case-record form and managed by Microsoft Office Excel. Statistical analyses will be performed using SPSS.

  Pre-dose through 60 minutes post-dose

• Patient-ventilator asynchrony - time data

  Data will be collected in case-record form and managed by Microsoft Office Excel. Statistical analyses will be performed using SPSS.

  Pre-dose through 60 minutes post-dose

• The degree of neuromuscular block by train-of-four-watch monitor - time data

  Data will be collected in case-record form and managed by Microsoft Office Excel. Statistical analyses will be performed using SPSS.

  Pre-dose through 60 minutes post-dose

Secondary Outcomes (7)

• Time to maximum concentration

  Pre-dose through 60 minutes post-dose

• Half-life

  Pre-dose through 60 minutes post-dose

• Clearance

  Pre-dose through 60 minutes post-dose

• Elimination rate constant

  Pre-dose through 60 minutes post-dose

• Time to maximum block

  Pre-dose through 60 minutes post-dose

Other Outcomes (1)

• Bispectral index (BIS) - time data

  Pre-dose through 60 minutes post-dose

Study Arms (1)

Cisatracurium

EXPERIMENTAL

Patients who require paralysis with cisatracurium as part of their clinical care in ICU

Drug: cisatracurium

Interventions

cisatracurium DRUG

A single dose of 0.2 mg/kg intravenous bolus cisatracurium will be administered and blood samples will be taken before and at least 7 occasions post dose (at 1, 5, 10, 12, 15, 20, 30, and/or 60 minutes after a single bolus).

Also known as: Nimbex

Cisatracurium

Eligibility Criteria

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

You may qualify if:

• Age greater than 18 years
• Admission for ICU care
• Require paralysis with cisatracurium as part of their clinical care
• Patients or legal representatives who are able to understand and are willing and able to give their signed informed consent before any trial-related procedures are performed

You may not qualify if:

• Lactating women
• Pregnancy women
• Documented history of hypersensitivity to cisatracurium
• Pre-existing neuromuscular disease
• Patients with burn lesions
• Currently diagnosed of hypothermia condition (tympanic body temperature ≤ 36 °C)
• Patients currently receiving intravenous bolus or push of cisatracurium within 24 hours or receiving intravenous continuous infusion of cisatracurium within 48 hours prior to enrollment
• Patients who have to receive intravenous continuous infusion of cisatracurium within 30 minutes after given intravenous bolus of 0.2 mg/ kg cisatracurium

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Related Publications (11)

• Liu X, Kruger PS, Weiss M, Roberts MS. The pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients with severe sepsis. Br J Clin Pharmacol. 2012 May;73(5):741-9. doi: 10.1111/j.1365-2125.2011.04149.x.

  PMID: 22114771 BACKGROUND

• Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, McGee W, McManus C, Meade M, Nix S, Patterson A, Sands MK, Pino R, Tescher A, Arbour R, Rochwerg B, Murray CF, Mehta S. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016 Nov;44(11):2079-2103. doi: 10.1097/CCM.0000000000002027.

  PMID: 27755068 BACKGROUND

• Gainnier M, Roch A, Forel JM, Thirion X, Arnal JM, Donati S, Papazian L. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2004 Jan;32(1):113-9. doi: 10.1097/01.CCM.0000104114.72614.BC.

  PMID: 14707568 BACKGROUND

• Greenberg SB, Vender J. The use of neuromuscular blocking agents in the ICU: where are we now? Crit Care Med. 2013 May;41(5):1332-44. doi: 10.1097/CCM.0b013e31828ce07c.

  PMID: 23591211 BACKGROUND

• Forel JM, Roch A, Marin V, Michelet P, Demory D, Blache JL, Perrin G, Gainnier M, Bongrand P, Papazian L. Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2006 Nov;34(11):2749-57. doi: 10.1097/01.CCM.0000239435.87433.0D.

  PMID: 16932229 BACKGROUND

• Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.

  PMID: 20843245 BACKGROUND

• Dieye E, Minville V, Asehnoune K, Conil C, Georges B, Cougot P, Fourcade O, Conil JM. Pharmacodynamics of cisatracurium in the intensive care unit: an observational study. Ann Intensive Care. 2014 Feb 11;4(1):3. doi: 10.1186/2110-5820-4-3.

  PMID: 24521394 BACKGROUND

• Murray MJ, Cowen J, DeBlock H, Erstad B, Gray AW Jr, Tescher AN, McGee WT, Prielipp RC, Susla G, Jacobi J, Nasraway SA Jr, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists, American College of Chest Physicians. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med. 2002 Jan;30(1):142-56. doi: 10.1097/00003246-200201000-00021. No abstract available.

  PMID: 11902255 BACKGROUND

• Welch RM, Brown A, Ravitch J, Dahl R. The in vitro degradation of cisatracurium, the R, cis-R'-isomer of atracurium, in human and rat plasma. Clin Pharmacol Ther. 1995 Aug;58(2):132-42. doi: 10.1016/0009-9236(95)90190-6.

  PMID: 7648763 BACKGROUND

• McManus MC. Neuromuscular blockers in surgery and intensive care, Part 1. Am J Health Syst Pharm. 2001 Dec 1;58(23):2287-99. doi: 10.1093/ajhp/58.23.2287.

  PMID: 11763807 BACKGROUND

• Panusitthikorn P, Suthisisang C, Tangsujaritvijit V, Nosoongnoen W, Dilokpattanamongkol P. Pharmacokinetics and pharmacodynamics studies of a loading dose of cisatracurium in critically ill patients with respiratory failure. BMC Anesthesiol. 2022 Jan 22;22(1):32. doi: 10.1186/s12871-022-01571-2.

  PMID: 35065599 DERIVED

MeSH Terms

Conditions

Critical Illness; Respiratory Distress Syndrome; Respiratory Insufficiency; Paralysis

Interventions

cisatracurium

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 9, 2017
• Study Start: December 15, 2017
• Primary Completion: August 31, 2018
• Study Completion: August 31, 2018
• Last Updated: March 6, 2019

Record last verified: 2019-03

Locations

TH (1)