Safety Analysis of Antimicrobial Pharmacotherapy in Intensive Care Unit at Pediatric Hospital

March 4, 2022 updated by: Anna Vlasova

Observational Prospective Multidirectional Study on the Safety of Antimicrobial Pharmacotherapy in Intensive Care Unit (ICU) Children Aged 0-17

Changes in the metabolic ability of cytochrome P-450 during child development can affect both bioavailability and elimination depending on the involvement of intestinal and hepatic metabolic processes. The age-related variability of cytochrome P-450 isoenzymes in children has been described since 2010. The variability in the development of the activity of specific cytochrome P-450 isoenzymes illustrates why the pharmacogenetic features of the medicine use at different age periods should be studied for individual drugs. This will provide an understanding of the mechanisms for preventing adverse events appearing in pediatric intensive care units while more common antimicrobial pharmacotherapy is administered. Improved knowledge of the pharmacogenetic characteristics of cytochrome P-450 and the unintended consequences of modulation of its isoenzymes could provide an understanding of the susceptibility to adverse events in children in critical conditions staying at Intensive Care unit (ICU).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

An observational prospective multidirectional study on the safety of antimicrobial pharmacotherapy in ICU children aged 0-17. The endpoints of the safety assessment are the frequency of adverse events with antimicrobial agents (AMA); electrocardiography (ECG), fibrinogen concentration, international normalized ratio (INR) and prothrombin index (IPT) at screening and at the end of the treatment course, and pharmacogenetic indicators (a more detailed study of the safety profile). A demonstration of the effectiveness of each of these comparisons of inequality will be based on the hypothesis testing approach, according to which the null hypothesis concludes that there is no difference between groups receiving different AMA combinations for the endpoint of interest; and an alternative hypothesis supposes a difference between treatment groups receiving different AMA combinations. Changes in the sequential organ failure assessment (SOFA) scale in dynamics compared to the baseline will be analyzed using the Mixed-Effect Model Repeated Measure (MMRM) model which assume the baseline, gender, age, AMA combination, and the duration of the AMA course. For a population of subjects aged 0-3 months, the analysis will be performed using the analysis of covariance (ANCOVA) model with the effects of INR, fibrinogen, and IPT values at the initial level for gender, age, and AMA combination in the treatment groups.

To assess the secondary endpoint for the general population - the frequency and timing of the transition to de-escalation at ICU, cluster analysis will be conducted to identify the relationship of specific AMA combinations with the possibility of de-escalation in ICU children.

Studies will be conducted to reveal the relationship in gene polymorphism encoding isoenzymes of the cytochrome P-450 biotransformation, and the relationship between the activity of transport proteins with the indicators of effectiveness and safety of antimicrobial pharmacotherapy. The lack of pharmacological safety studies in children administered medicine combinations to overcome pan-resistant gram-negative infection provides relevant prerequisites for this study.

Study Type

Observational

Enrollment (Actual)

100

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

  • Russian Federation
      • Moscow, Russian Federation, 119049
        • Morozov Children's City Clinical Hospital

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

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study will enroll the participants from the patients of the Intensive Care Unit at Morozov Children's City Clinical Hospital of the Moscow City Health Department, Moscow, Russian Federation.

Description

Inclusion Criteria:

  1. Intensive Care Unit (ICU) patient;
  2. Community-acquired infections with risk factors for multidrug-resistant pathogens (risk factors for extended-spectrum β-lactamase (ESBL) - type II;

  3. Nosocomial infections - type III:

    • IIIa: hospitalized during the period of 90 days, without prior antimicrobial agent (AMA) therapy outside the ICU (risk factors for ESBL);
    • IIIb: prolonged hospitalization (> 7 days) and/or stay at ICU for more than 3 days and/or previous AMA therapy (risk factors for ESBL, carbenicillin-resistant (CARB-R), nonfermenting Gram-negative bacteria (NFGNB), methicillin-resistant Staphylococcus aureus (MRSA));
  4. Nosocomial infections with a risk of invasive candidiasis - type IV (candida score ≥2 points);
  5. Written informed consent for medical intervention signed by at least one parent or caregiver (legal guardian) or informed consent of a patient under 15 years of age;
  6. Written informed consent for pharmacogenetic research signed by at least one parent or caregiver (legal guardian) or informed consent of a patient under 15 years of age.

Exclusion Criteria:

  1. Type I: patients with community-acquired infections and without risk factors for multidrug-resistant pathogens, without hospitalization during the previous 90 days;
  2. Previous/concomitant therapy is not significant;
  3. Children in the ward: children under guardianship are not eligible.

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

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1 (0-17 years)
We will observe the treatment course in ICU pediatric patients, register adverse events (AEs) and serious adverse events (SAEs) if occur, and assess patient health status at the end of the performed therapy.
Other: Pharmacogenetic test
Buccal swabs are a relatively non-invasive way to collect deoxyribonucleic acid (DNA) samples for testing. A buccal swab will be performed to collect DNA from the cells on the inside of a subject's cheek for phenotyping of CYP3A4.
Other Names:
  • Buccal swabs for pharmacogenetic testing
  • buccal smear

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events frequency
Time Frame: From baseline until the date of first documented progression, assessed up to 1 month
Registered adverse events in participants during the treatment course
From baseline until the date of first documented progression, assessed up to 1 month
ECG QT Interval change
Time Frame: Change from screening QT Interval at 1 month
Assessment of QT Interval change at the end of the AMA course comparing with screening measurement
Change from screening QT Interval at 1 month

Collaborators and Investigators

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

Sponsor

Anna Vlasova

Collaborators

Russian Medical Academy of Continuous Professional Education
Morozov Children's Municipal Clinical Hospital of the Moscow City Health Department State-Financed

Investigators

  • Principal Investigator: Anna Vlasova, PhD, MD, Morozov Children's City Clinical Hospital of the Moscow City Health Department

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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 (Actual)

February 1, 2020

Primary Completion (Actual)

August 28, 2021

Study Completion (Actual)

October 15, 2021

Study Registration Dates

First Submitted

October 9, 2019

First Submitted That Met QC Criteria

October 24, 2019

First Posted (Actual)

October 28, 2019

Study Record Updates

Last Update Posted (Actual)

March 18, 2022

Last Update Submitted That Met QC Criteria

March 4, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 07819001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

De-identified individual participant data will be made available partially upon a request.

IPD Sharing Time Frame

Data will be available within 6 months of study completion.

IPD Sharing Access Criteria

Data Access Requests will be reviewed by the Independent Local Review Board. Requestors will be required to sign a Data Access Agreement.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Clinical Study Report (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

product manufactured in and exported from the U.S.

No

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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