Pharmacotherapy Personalization of Cancer Patients

Pharmacotherapy Personalization of Cancer Patients Based on Modern Analytical and Computational Techniques

Treatment personalization could ensure better outcome than standard procedures. It is particularly important in intensive care units where patients received many drugs and procedures. Their health status can change very fast. The oncologic patients treated in intensive care units are a special group of patients. Factors related to cancer influence extra their health status. The aim of this study is population pharmacokinetic-pharmacodynamic analysis drugs that are routinely used during an analgosedation in ICU oncologic patients. Analgosedation is monitored by drugs plasma concentration, the depth of sedation (bispectral index) and vital parameters like: systolic and diastolic blood pressure, mean arterial pressure, heart rate. Moreover, the TNM Staging System, biochemical parameters, The American Society of Anesthesiologists (ASA) physical status classification will be checked like potential factors influencing on pharmacokinetics and pharmacodynamics drugs used in the study.

Study Overview

• Status: Completed
• Conditions: Head and Neck Neoplasms; Oncologic Patients
• Intervention / Treatment: Drug: Infusion Intravenous

Detailed Description

The oncologic patients are qualified to head and neck tumor resection in general anesthesia. The anesthesia introduction is performed with single dose of midazolam, fentanyl, rocuronium and propofol/etomidate. Sevoflurane is used in anesthesia maintenance. Patients are transported to ICU after operation. Then they are kept for several hours in analgosedation. All used drugs are given by intravenous continuous infusion. Oxycodone is an analgesic component of analgosedation. Midazolam, dexmedetomidine and/or propofol are used as sedatives (2-3 drugs in every patient). Whole blood samples (2.0 ml) are collected during the study to measure drugs concentrations - 3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation. Vital parameters and bispectral index are monitored during analgosedation and 6 hours after the infusion cessation and noted every 15-60 minutes.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• Poland
  • Greater Poland
    • Poznan, Greater Poland, Poland, 61-866
      • Greater Poland Cancer Centre
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-416
      • Medical University of Gdansk

Participation Criteria

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

The adult patients with recognition of head and neck tumor who are qualified to tumor resection in general anesthesia and needing analgosedation in ICU after operation.

Description

Inclusion Criteria:

• age over 18 years old,
• qualifications to oncologic surgery,
• needing of analgosedation in ICU after an operation

Exclusion Criteria:

• proven allergies to used in anesthetics or/analgosedation medicaments,
• lack of written confirmed consent of a patient

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Analgosedation in ICU patients after head and neck tumor resection in general anesthesia; Head and neck tumor resections were performed in general anesthesia. Midazolam and etomidate or propofol were used in introduction and then anesthesia was maintenance with sevoflurane. Patients received intravenous continuous infusion of oxycodone as an analgesic component and sedatives (propofol/dexmedetomidine/midazolam) during analgosedation in ICU.

Drug: Infusion Intravenous; Other Names: Analgesics and sedatives intravenous continuous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the depth of sedation using bispectral index	Continuous measurement of the depth of sedation using bispectral index during analgosedation in intensive care unit.	from the beginning of analgosedation to 6 hours after analgosedation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxycodone plasma concentrations [ng/ml]	Measurements of oxycodone and noroxycodone plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol.	3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation
Dexmedetomidine plasma concentrations [ng/ml]	Measurements of dexmedetomidine plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol.	3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation
Midazolam plasma concentrations [ng/ml]	Measurements of midazolam and alfa-hydroxymidazolam plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol.	3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation
Propofol plasma concentrations [ng/ml]	Measurements of propofol plasma concentrations [ng/ml] during and after analgosedation. Whole blood samples (2.0 ml) were collected according to the study protocol.	3-4 times during infusion, 5, 10, 15, 30, 60 minutes and 2, 4, 6 hours after the infusion cessation
Systolic blood pressure	Measurements of systolic blood pressure during analgosedation in intensive care unit.	before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation
Diastolic blood pressure	Measurements of diastolic blood pressure during analgosedation in intensive care unit.	before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation
Heart rate	Measurements of heart rate during analgosedation in intensive care unit.	before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation
Mean arterial pressure	Measurements of mean arterial pressure during analgosedation in intensive care unit.	before the beginning of analgosedation, during analgosedation, up to 6 hours after analgosedation

Collaborators and Investigators

• Sponsor: Poznan University of Medical Sciences
• Collaborators: Medical University of Gdansk; The Greater Poland Cancer Centre
• Investigators: Principal Investigator: Agnieszka Bienert, MSC, PhD, Poznan University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Anesthesia; Pharmacodynamics; Intensive Care Units; Surgical patients; Analgosedation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics
• Other Study ID Numbers: 763/2016; 2015/17/B/NZ7/03032 (Other Grant/Funding Number: Polish National Science Centre)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: pharmacokinetic and pharmacodynamic data (concentration/effect/time profiles) of individuals will be available
• IPD Sharing Time Frame: The data will be available in 6-12 months and available for 5 years
• IPD Sharing Access Criteria: Scientists
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No