Pharmacodynamic Interaction of REMI and DMED

NCT03143972 | Completed Phase 4

• 1 other identifier: PIRAD-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The objective is to map the pharmacokinetic / pharmacodynamic interaction between dexmedetomidine and remifentanil by observing changes in anesthetic depth. These changes will be related to drug concentrations using pharmacokinetic/pharmacodynamic (PKPD) modeling.

Conditions

Anesthesia

Keywords

Dexmedetomidine; Remifentanil; Pharmacodynamics; Interaction

Outcome Measures

Primary Outcomes (1)

• Tolerance of Laryngoscopy (TOL)

  Tolerance of a laryngoscopy (yes/no) will be tested at the end of each infusion step during both studydays, when MOAA/s is 0 / 1 and will be related to the drug concentration(s).

  35 - 255 minutes

Secondary Outcomes (3)

• Modified observer's assessment of alertness and sedation scale (MOAA/s)

  During anesthesia sessions day 1 and day 2

• Electrical stimulus

  During anesthesia sessions day 1 and day 2

• Electroencephalogram (EEG)

  During anesthesia sessions day 1 and day 2

Study Arms (3)

Dexmedetomidine only

EXPERIMENTAL

Dexmedetomidine will be administered by effect-site TCI according to the Hannivoort model extended with an effect-site rate constant of 0.0428min-1. A stepwise increasing dosing regimen will be given, with concentrations targeting an effect site concentration of 1 ng/ml (40 min), 3 ng/ml (50 min), 4 ng/ml (40 min), 5 ng/ml (40 min) and 8 ng/ml (70 min).

Drug: Dexmedetomidine

Remifentanil only

EXPERIMENTAL

Remifentanil will be administered by effect-site TCI according to the Eleveld model. A stepwise increasing dosing regimen will be given, with concentrations targeting an effect site concentration of 1 ng/ml (12 min), 2 ng/ml (12 min), 3 ng/ml (12 min), 5 ng/ml (12 min) and 7 ng/ml (12 min).

Drug: Remifentanil

Dexmedetomidine-Remifentanil interaction

EXPERIMENTAL

A fixed background dose of dexmedetomidine will be given, this will be calculated after the first 5 subjects completed the dexmedetomidine only session. It will be set to 50% of the observed mean EC50TOL (Tolerance of Laryngoscopy). Remifentanil infusion will be administered by effect site TCI with stepwise increasing targets of 0.5 - 1.0 - 1.5 - 2.0 - 2.5 - 3.0 - 4.0 ng/ml, each lasting for 15 minutes.

Drug: Dexmedetomidine; Drug: Remifentanil

Interventions

Dexmedetomidine DRUG

Single drug administration

Also known as: Dexdor

Dexmedetomidine only; Dexmedetomidine-Remifentanil interaction

Remifentanil DRUG

Single drug administration

Also known as: Ultiva

Dexmedetomidine-Remifentanil interaction; Remifentanil only

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American Society of Anesthesiologists (ASA) Physical Status 1
• No medical history of significance
• No chronic use of medication, drugs, tobacco or more than 20 gr alcohol daily (oral contraceptives excluded).
• Concerning the cognitive function: Volunteers are considered to have sufficient cognitive reserve if they are able to read and comprehend the patient information form, if they can adequately answer the anamnestic questions during the screening process and if they are allowed to provide legitimate written informed consent.
• No selection will be made regarding ethnic background

You may not qualify if:

• Known intolerance to dexmedetomidine or remifentanil
• Volunteer refusal
• Age \< 18 years or \>70 years
• Pregnancy, or currently nursing
• Hairstyle with dreadlocks (EEG-monitoring will not be possible)
• Body mass index (BMI) \<18 or \>30 kg/m2.
• Neurological disorder (epilepsy, the presence of a brain tumor, a history of brain surgery, hydrocephalic disorders, depression needing treatment with anti-depressive drugs, a history of brain trauma, a subarachnoidal bleeding, TIA or cerebral infarct, psychosis or dementia , schizophrenia, alcohol or drug abuse).
• Diseases involving the cardiovascular system (hypertension, coronary artery disease, prior acute myocardial infarction, any valvular and/or myocardial disease involving

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713EZ, Netherlands

Location

Related Publications (6)

• Hannivoort LN, Eleveld DJ, Proost JH, Reyntjens KM, Absalom AR, Vereecke HE, Struys MM. Development of an Optimized Pharmacokinetic Model of Dexmedetomidine Using Target-controlled Infusion in Healthy Volunteers. Anesthesiology. 2015 Aug;123(2):357-67. doi: 10.1097/ALN.0000000000000740.

  PMID: 26068206 BACKGROUND

• Su H, Koomen JV, Eleveld DJ, Struys MMRF, Colin PJ. Pharmacodynamic mechanism-based interaction model for the haemodynamic effects of remifentanil and propofol in healthy volunteers. Br J Anaesth. 2023 Aug;131(2):222-233. doi: 10.1016/j.bja.2023.04.043. Epub 2023 Jun 22.

  PMID: 37355412 DERIVED

• Ramaswamy SM, Kuizenga MH, Weerink MAS, Vereecke HEM, Struys MMRF, Belur Nagaraj S. Frontal electroencephalogram based drug, sex, and age independent sedation level prediction using non-linear machine learning algorithms. J Clin Monit Comput. 2022 Feb;36(1):121-130. doi: 10.1007/s10877-020-00627-3. Epub 2020 Dec 14.

  PMID: 33315176 DERIVED

• Ramaswamy SM, Weerink MAS, Struys MMRF, Nagaraj SB. Dexmedetomidine-induced deep sedation mimics non-rapid eye movement stage 3 sleep: large-scale validation using machine learning. Sleep. 2021 Feb 12;44(2):zsaa167. doi: 10.1093/sleep/zsaa167.

  PMID: 32860500 DERIVED

• Belur Nagaraj S, Ramaswamy SM, Weerink MAS, Struys MMRF. Predicting Deep Hypnotic State From Sleep Brain Rhythms Using Deep Learning: A Data-Repurposing Approach. Anesth Analg. 2020 May;130(5):1211-1221. doi: 10.1213/ANE.0000000000004651.

  PMID: 32287128 DERIVED

• Ramaswamy SM, Kuizenga MH, Weerink MAS, Vereecke HEM, Struys MMRF, Nagaraj SB. Novel drug-independent sedation level estimation based on machine learning of quantitative frontal electroencephalogram features in healthy volunteers. Br J Anaesth. 2019 Oct;123(4):479-487. doi: 10.1016/j.bja.2019.06.004. Epub 2019 Jul 18.

  PMID: 31326088 DERIVED

MeSH Terms

Interventions

Dexmedetomidine; Remifentanil

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines

Study Officials

• Michel MR Struys, Prof.Dr.

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All volunteers will receive 2 standardized anesthesia sessions with a washout period of at least one week between sessions. During the first session volunteers will receive dexmedetomidine, during the second session they will first receive remifentanil and afterwards the combination of drugs will be administered. Anesthetic depth will be evaluated by MOAA/S scores (see table 2), testing of tolerance to electrical stimuli and laryngoscopy. Furthermore multichannel EEG-data will be collected to get insight in the drug dependent characteristics. Measured effects will be related to drug plasma concentrations.

Study Record Dates

• First Submitted: March 14, 2017
• First Posted: May 8, 2017
• Study Start: June 28, 2017
• Primary Completion: February 23, 2018
• Study Completion: February 23, 2018
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

NL (1)