AzTrials
AzTrials

AnesthesiaPhase 4NCT02544854

Pharmacokinetic/Pharmacodynamic Model of Propofol in Children

A Phase 4 study testing Propofol in people with Anesthesia, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

By measuring plasmatic concentration of propofol at different intervals during surgery of children aged 1 to 12 years old and measuring Bispectral Index (BIS) as a surrogate for cerebral activity, the investigators aim to create a pharmacokinetic/pharmacodynamic model of propofol for children. Read more about this study

Who is it for?
Ages 1 year to 12 yearsHealthy volunteers can take part
Conditions the study is for
Anesthesia
What is being tested?
Propofol
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteChile
Study dates
Sep 2015to Dec 2016
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 1 year to 12 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • Children aged 1 year through 11 years 11 months and 29 days old.
  • American Society of Anesthesiology (ASA) score 1 or 2.
  • Elective surgery of more than 1 hour of expected duration.
  • Written informed consent signed by parents or legal guardians.
  • Oral and written consent in children aged over 7 years old.

Who cannot join

  • Known allergies to study drugs.
  • Use of any medication acting on central nervous system in the last 24 hours previous to surgery.
  • Chronic cardiac, renal, hepatic or neurologic disease that determines abnormal function.
  • Difficult airway (predicted or known).
  • Use of neuraxial anesthesia.

Trial locations and contacts

1 site in 1 country.

Ricardo Fuentes, MD contact

56-9-77648344

rfuente@med.puc.cl

Chile1 site, 1 recruiting

  • Division de Anestesia - Pontificia Universidad Catolica de Chile

    Santiago, Santiago Metropolitan, 8330024

    Fernando R Altermatt, MSc, 56-2-23543270, fernando.altermatt@gmail.com

    Hernan E Auad, MD, 56-2-23543270, hernan_auad@hotmail.com

    Recruiting

Other trials in Chile

About this study

By measuring plasmatic concentration of propofol at different intervals during surgery of children aged 1 to 12 years old and measuring Bispectral Index (BIS) as a surrogate for cerebral activity, the investigators aim to create a pharmacokinetic/pharmacodynamic model of propofol for children.

Read the detailed description

Propofol is an intravenous anesthetic capable of providing a safe general anesthesia, free from many of the adverse effects associated with inhalation anesthetics (postoperative nausea and vomiting, agitation on awakening, seizures and trigger malignant hyperthermia crisis) and widely used in adults, but even less so in children. This is due to the fact that its pharmacological characteristics have not been clarified at all in the pediatric population.

The physiological maturation of different systems in children, as well as changes in body composition and metabolism may determine significant changes in the pharmacokinetics (distribution volumes and clearance) of children. Moreover, within the same age group, variations across different individuals may make even less predictable the pharmacokinetic models currently in use. Indeed, previous work in our group based on these models have shown that propofol dosage required by children to induce general anesthesia is inversely proportional to the age, which could be explained by biases in these models, different sensitivity to propofol at different ages and sizes, etc.

The effect of propofol in the brain is described by its pharmacodynamics, but in children this is still in debate. Using a brain activity monitor (BIS), the effect of propofol at the central nervous system can be analyzed under a model of nonlinear mixed effects (NONMEM) and establish the time to peak effect to characterize in detail the pharmacodynamics of this drug.

Integrating pharmacokinetic and pharmacodynamic data, a pharmacokinetic/pharmacodynamic (PK/PD) model for the pediatric population can be derived.

The aim of this paper is to describe the first PK / PD model of propofol in children, valid for different ages and to analyze them in the context of different body composition parameters.

The importance of this study is that its results will publish the missing link in the pediatric pharmacology of propofol, which will encourage more research and more widespread use of this technique in the pediatric population.

Conditions
Anesthesia
Being tested
Propofol
Keywords
Pharmacokinetics, pharmacodynamics, propofol, pediatrics

What participants receive

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

  • PropofolDrug

    Also called Diprivan

    Propofol infusion will be started after inhalational induction by manual infusion by the following scheme:

    1. First 15 minutes: 15 mg/kg/min
    2. 16 to 30 minutes: 13 mg/kg/min
    3. 31 to 60 minutes: 11 mg/kg/min
    4. 61 to 120 minutes: 10 mg/kg/min Dose will be titrated to maintain BIS between 40 - 50.

    Venous sampling for plasmatic levels of propofol measuring will be made at the following moments:

    1. 5, 15 and 25 minutes of starting infusion,
    2. 1, 3, 5, 7, 9 and 12 minutes of bolus and,
    3. 5, 25, 60 and 120 minutes of infusion ended.
Study groups in NCT02544854
Study groupRoleWhat they receive
Ages 1 year - 3 years 11 monthsExperimentalPropofol infusion, measuring of plasmatic levels of propofol through venous sampling
Receives: Drug: Propofol
Ages 4 years - 8 years 11 monthsExperimentalPropofol infusion, measuring of plasmatic levels of propofol through venous sampling
Receives: Drug: Propofol
Ages 9 years - 11 years 11 monthsExperimentalPropofol infusion, measuring of plasmatic levels of propofol through venous sampling
Receives: Drug: Propofol

What is being measured

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

  1. Propofol plasmatic levels

    Measured by high pressure liquid chromatography

    Measured: From start of infusion: 5 min, 15 min, 45 min; from bolus 0 min, 1 min, 3 min, 5 min, 10 min; after infusion 30 min, 60 min, 120 min, 360 min

Secondary outcomes (5)

  1. Hemodynamics

    Heart rate and arterial pressure

    Measured: Entering operating room up to end of anesthesia

  2. Propofol total dose

    Measured in milligrams

    Measured: Start of propofol infusion until it ends

  3. Sevoflurane total dose

    Measured: Start of inhalational induction to zero end tidal concentration

  4. Pulse oximetry

    Measured: Entering operating room up to end of anesthesia

  5. BIS

    Depth of anesthesia will be recorded with BIS monitor

    Measured: Entering operating room up to end of anesthesia

Timeline

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

  1. First posted9 Sep 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionDec 2016 (estimated)
  4. Study completionDec 2016 (estimated)

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
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02544854
Sponsor's protocol ID
15-068
Status last verified
Oct 2016
First submitted
6 Sep 2015
Last updated
12 Oct 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Gibert S, Sabourdin N, Louvet N, Moutard ML, Piat V, Guye ML, Rigouzzo A, Constant I. Epileptogenic effect of sevoflurane: determination of the minimal alveolar concentration of sevoflurane associated with major epileptoid signs in children. Anesthesiology. 2012 Dec;117(6):1253-61. doi: 10.1097/ALN.0b013e318273e272.

    PubMed 23103557

  • Kearns GL, Reed MD. Clinical pharmacokinetics in infants and children. A reappraisal. Clin Pharmacokinet. 1989;17 Suppl 1:29-67. doi: 10.2165/00003088-198900171-00005.

    PubMed 2692939

  • Fuentes R, Cortinez I, Ibacache M, Concha M, Munoz H. Propofol concentration to induce general anesthesia in children aged 3-11 years with the Kataria effect-site model. Paediatr Anaesth. 2015 Jun;25(6):554-9. doi: 10.1111/pan.12657. Epub 2015 Apr 16.

    PubMed 25880448

  • Rigouzzo A, Servin F, Constant I. Pharmacokinetic-pharmacodynamic modeling of propofol in children. Anesthesiology. 2010 Aug;113(2):343-52. doi: 10.1097/ALN.0b013e3181e4f4ca.

    PubMed 20613468

  • Coppens MJ, Eleveld DJ, Proost JH, Marks LA, Van Bocxlaer JF, Vereecke H, Absalom AR, Struys MM. An evaluation of using population pharmacokinetic models to estimate pharmacodynamic parameters for propofol and bispectral index in children. Anesthesiology. 2011 Jul;115(1):83-93. doi: 10.1097/ALN.0b013e31821a8d80.

    PubMed 21555936

  • Panchatsharam S, Callaghan M, Day R, Sury MR. Measured versus predicted blood propofol concentrations in children during scoliosis surgery. Anesth Analg. 2014 Nov;119(5):1150-7. doi: 10.1213/ANE.0000000000000413.

    PubMed 25225889

  • Howie SR. Blood sample volumes in child health research: review of safe limits. Bull World Health Organ. 2011 Jan 1;89(1):46-53. doi: 10.2471/BLT.10.080010. Epub 2010 Sep 10.

    PubMed 21346890

  • Fuentes R, Cortinez LI, Contreras V, Ibacache M, Anderson BJ. Propofol pharmacokinetic and pharmacodynamic profile and its electroencephalographic interaction with remifentanil in children. Paediatr Anaesth. 2018 Dec;28(12):1078-1086. doi: 10.1111/pan.13486. Epub 2018 Oct 11.

    PubMed 30307663

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Propofol in people with Anesthesia, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.

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 5 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 12 Oct 2016. 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 Chile. 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?

Results are not available in the source record.

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

Contact Ricardo Fuentes, MD (56-9-77648344, rfuente@med.puc.cl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Propofol plasmatic levels (time frame: From start of infusion: 5 min, 15 min, 45 min; from bolus 0 min, 1 min, 3 min, 5 min, 10 min; after infusion 30 min, 60 min, 120 min, 360 min). 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 NCT02544854, which also lists 8 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 12 Oct 2016.

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