Midazolam Whole Body Physiologically Based Pharmacokinetic Model (MidPBPK)

May 23, 2017 updated by: Paolo Severgnini, Università degli Studi dell'Insubria

Whole Body Physiologically Based Pharmacokinetic (PBPK) Model to Estimate Cerebral and Systemic Midazolam Concentrations in ICU Patients Under Sedation.

This study investigates what independent variables may influence Midazolam Pharmacokinetics in critically ill patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study has three specific aims:

  1. to create a Midazolam PBPK model based on anthropometric and physiopathological data from enrolled patients;
  2. to estimate cerebral and systemic Midazolam concentrations;
  3. to assess independent variables about Midazolam pharmacokinetic in critically ill patients.

Study Type

Observational

Enrollment (Actual)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Varese, Italy, 21100
        • Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Critically ill patients in Intensive Care Unit, mechanically ventilated, sedated with midazolam, intravenous continued perfusion.

Description

Inclusion Criteria:

  • ICU admittance
  • Caucasian
  • Clinical indication of least 72h of continuous sedation with Midazolam
  • MAP between 60 - 150 mmHg, even if obtained with amine support
  • informed consent obtained

Exclusion Criteria:

  • Any endocranial lesion, spontaneous or induced
  • PaCO2 > 60 mmHg or < 30 mmHg
  • PaO2 < 50 mmHg
  • Pregnancy
  • Anuria
  • Any transplantation
  • Severe hepatic failure (Child C)
  • Life expectancy < 72h
  • Ketoconazole and antiretrovirals in therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Midazolam

Patients will be enrolled within 24h from the beginning of continuous Midazolam perfusion.

Blood and urine sampling will follow this schedule:

  • 24h: blood (3ml)
  • 48h: blood (3ml) and urine
  • End of infusion: blood (3ml)
  • 6h after end of infusion: blood (3ml) and urine.

Blood samples will be centrifuged for 10 minutes at 3300rpm, then supernatant will be placed into test tubes and stored at -20°C; urine samples will be freeze at -20°C as well.

Then all frozen samples will be analyzed to get Midazolam concentrations.
Procedure: Blood and urine sampling

Blood and urine sampling will follow this schedule:

  • 24h: blood (3ml)
  • 48h: blood (3ml) and urine
  • End of infusion: blood (3ml)
  • 6h after end of infusion: blood (3ml) and urine. Blood samples will be centrifuged for 10 minutes at 3300rpm, then supernatant will be placed into test tubes and stored at -20°C; urine samples will be freeze at -20°C as well.

Then all frozen samples will be analyzed to get Midazolam concentrations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Midazolam concentration in serum and urine
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks

We will calculate Midazolam AUC in serum and urine using blood and urine samples. With this data we will evaluate the elimination constants and create a Physiologically Based Pharmacokinetic Model for Midazolam simulating the drug concentration profile in brain and fat tissue.

The blood and urine samples timing is:

  • 1 blood sample will be gathered after 24h at the beginning of continuous intravenous infusion of Midazolam
  • 1 blood sample and 1 urine sample will be gathered after 48h at the beginning of continuous intravenous infusion of Midazolam
  • 1 blood sample will be gathered at the end of continuous intravenous infusion of Midazolam (the duration of infusion is different for each patient according with clinical case)
  • 1 blood sample and 1 urine sample will be gathered after 6h at the end of continuous intravenous infusion of Midazolam (the duration of infusion is different for each patient according with clinical case)
Participants will be followed for the duration of hospital stay, an expected average of 3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fat mass analysis and its importance in drug distribution.
Time Frame: At enrollment
At enrollment we will collect data about fat mass in our population. Our goal is to determine how much this variable can modify the distribution of Midazolam in the body. Statistical analysis will performed to found if different body mass values are correlated with different blood concentration of Midazolam at steady level.
At enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Università degli Studi dell'Insubria

Collaborators

University of Milan

Investigators

  • Principal Investigator: Paolo Severgnini, Prof., Università degli Studi dell'Insubria, Varese, Italy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

August 19, 2012

First Submitted That Met QC Criteria

October 25, 2013

First Posted (Estimate)

November 1, 2013

Study Record Updates

Last Update Posted (Actual)

May 25, 2017

Last Update Submitted That Met QC Criteria

May 23, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 724

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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