Midazolam Whole Body Physiologically Based Pharmacokinetic Model

NCT01973894 | Completed DMC

• 1 other identifier: 724
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Respiratory Failure; Coma

Keywords

PBPK; Midazolam; Pharmacokinetics; Critically ill patients

Outcome Measures

Primary Outcomes (1)

• Midazolam concentration in serum and urine

  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 Outcomes (1)

• Fat mass analysis and its importance in drug distribution.

  At enrollment

Study Arms (1)

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

Interventions

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.

Midazolam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Università degli Studi dell'Insubria: lead
• University of Milan: collaborator

Study Sites (1)

Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum and urine

MeSH Terms

Conditions

Respiratory Insufficiency; Coma

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Paolo Severgnini, Prof.

  Università degli Studi dell'Insubria, Varese, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: August 19, 2012
• First Posted: November 1, 2013
• Study Start: January 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: May 25, 2017

Record last verified: 2017-05

Locations

IT (1)