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Completed

NCT Number: NCT01973894

Midazolam Whole Body Physiologically Based Pharmacokinetic Model

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

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Key information

Conditions

Respiratory Failure Coma Consciousness Disorders Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Pathological Conditions, Signs and Symptoms Respiration Disorders Respiratory Insufficiency Respiratory Tract Diseases Signs and Symptoms Unconsciousness

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

About this study

This study has three specific aims:

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Blood and urine sampling

Procedure

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.

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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.

Sponsors and collaborators

Lead sponsor

Università degli Studi dell'Insubria

Other

Collaborators

  • University of Milan

Registry information

Official study title

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

Acronym: MidPBPK

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Nov 1, 2013
Registry last updated
May 25, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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