AzTrials
AzTrials

AnesthesiaPhase 4PIRADNCT03143972

Pharmacodynamic Interaction of REMI and DMED

A Phase 4 study testing Dexmedetomidine and Remifentanil in people with Anesthesia, run by University Medical Center Groningen at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Anesthesia
What is being tested?
Dexmedetomidine and Remifentanil
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteNetherlands
Study dates
28 Jun 2017to 23 Feb 2018
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
  • No exclusion criterium is present

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • University Medical Center Groningen

    Groningen, 9713EZ

Other trials in Netherlands

About this study

Official title: Pharmacodynamic Interactions Between Remifentanil and Dexmedetomidine (PIRAD)

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.

Read the detailed description

This study is designed to investigate whether the use of a combination of dexmedetomidine and remifentanil is clinically useful to provide anesthesia during surgical and diagnostic procedures and whether it could be used for anesthetic induction. Furthermore the aim is to gain better insights in the required dosing regimens, the inter-individual variability in response towards the combination and the associated side effects. Better characterization of this drug-drug interaction will presumably lead to more precise dosing regimens, which in turn, will lead to a reduction in the occurrence of oversedation, side effects and recovery times.

The objective is to map the pharmacokinetic / pharmacodynamic interaction between dexmedetomidine and remifentanil by observing changes in anesthetic depth, measured by hypnotic and analgesic endpoints such as modified observer's assessment of alertness and sedation scale (MOAA/S), response to electrical stimuli, response to laryngoscopy and electroencephalogram (EEG) derived indices. These effects will be related to drug concentrations using pharmacokinetic/pharmacodynamic (PKPD) modeling.

Conditions
Anesthesia
Keywords
Dexmedetomidine, Remifentanil, Pharmacodynamics, Interaction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03143972
Study groupRoleWhat they receive
Dexmedetomidine onlyExperimentalDexmedetomidine 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).
Receives: Drug: Dexmedetomidine
Remifentanil onlyExperimentalRemifentanil 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).
Receives: Drug: Remifentanil
Dexmedetomidine-Remifentanil interactionExperimentalA 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.
Receives: Drug: Dexmedetomidine; Drug: Remifentanil

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 35 - 255 minutes

Secondary outcomes (3)

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

    An hypnotic endpoint measuring depth of anesthesia.

    Measured: During anesthesia sessions day 1 and day 2

  2. Electrical stimulus

    Measuring analgesia by observing response to a standardized electrical stimulus

    Measured: During anesthesia sessions day 1 and day 2

  3. Electroencephalogram (EEG)

    A multichannel electroencephalogram will be recorded

    Measured: During anesthesia sessions day 1 and day 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2017
  2. Study start28 Jun 2017
  3. Primary completion23 Feb 2018
  4. Study completion23 Feb 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Supportive care
Allocation
Non-randomised
Intervention model
Crossover
Model description
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.
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03143972
Sponsor's protocol ID
PIRAD-001
Acronym
PIRAD
Status last verified
Apr 2024
First submitted
14 Mar 2017
Last updated
18 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Anonimous data might be shared with other research groups

Publications

  • 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.

    PubMed 26068206

  • 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.

    PubMed 37355412

  • 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.

    PubMed 33315176

  • 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.

    PubMed 32860500

  • 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.

    PubMed 32287128

  • 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.

    PubMed 31326088

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dexmedetomidine and Remifentanil in people with Anesthesia, run by University Medical Center Groningen at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerance of Laryngoscopy (TOL) (time frame: 35 - 255 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03143972, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in