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

NCT04141657 | Completed

• 1 other identifier: 07819001
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Drug Therapy

Keywords

neonates; antimicrobial pharmacotherapy; pharmacotherapy adverse events; neonatal Intensive Care Unit; safety

Outcome Measures

Primary Outcomes (2)

• Adverse events frequency

  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

  Assessment of QT Interval change at the end of the AMA course comparing with screening measurement

  Change from screening QT Interval at 1 month

Study Arms (1)

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

Interventions

Pharmacogenetic test OTHER

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.

Also known as: Buccal swabs for pharmacogenetic testing, buccal smear

Group 1 (0-17 years)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• Intensive Care Unit (ICU) patient;
• Community-acquired infections with risk factors for multidrug-resistant pathogens (risk factors for extended-spectrum β-lactamase (ESBL) - type II;
• 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));
• Nosocomial infections with a risk of invasive candidiasis - type IV (candida score ≥2 points);
• 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;
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Anna Vlasova: lead
• Russian Medical Academy of Continuous Professional Education: collaborator
• Morozov Children's Municipal Clinical Hospital of the Moscow City Health Department State-Financed: collaborator

Study Sites (1)

Morozov Children's City Clinical Hospital

Moscow, 119049, Russia

Location

Related Publications (20)

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  PMID: 10797074 RESULT

• Schliamser SE, Broholm KA, Liljedahl AL, Norrby SR. Comparative neurotoxicity of benzylpenicillin, imipenem/cilastatin and FCE 22101, a new injectible penem. J Antimicrob Chemother. 1988 Nov;22(5):687-95. doi: 10.1093/jac/22.5.687.

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• Odio CM, Puig JR, Feris JM, Khan WN, Rodriguez WJ, McCracken GH Jr, Bradley JS. Prospective, randomized, investigator-blinded study of the efficacy and safety of meropenem vs. cefotaxime therapy in bacterial meningitis in children. Meropenem Meningitis Study Group. Pediatr Infect Dis J. 1999 Jul;18(7):581-90. doi: 10.1097/00006454-199907000-00004.

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• Cui L, Kasegawa H, Murakami Y, Hanaki H, Hiramatsu K. Postoperative toxic shock syndrome caused by a highly virulent methicillin-resistant Staphylococcus aureus strain. Scand J Infect Dis. 1999;31(2):208-9. doi: 10.1080/003655499750006326.

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• Karadeniz C, Oguz A, Canter B, Serdaroglu A. Incidence of seizures in pediatric cancer patients treated with imipenem/cilastatin. Pediatr Hematol Oncol. 2000 Oct-Nov;17(7):585-90. doi: 10.1080/08880010050122852.

  PMID: 11033734 RESULT

• Smith RG. Penicillin and cephalosporin drug allergies: a paradigm shift. J Am Podiatr Med Assoc. 2008 Nov-Dec;98(6):479-88. doi: 10.7547/0980479.

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• Laughon MM, Avant D, Tripathi N, Hornik CP, Cohen-Wolkowiez M, Clark RH, Smith PB, Rodriguez W. Drug labeling and exposure in neonates. JAMA Pediatr. 2014 Feb;168(2):130-6. doi: 10.1001/jamapediatrics.2013.4208.

  PMID: 24322269 RESULT

• Setiawan E, Suwannoi L, Montakantikul P, Chindavijak B. Optimization of Intermittent Vancomycin Dosage Regimens for Thai Critically Ill Population Infected by MRSA in the Era of the "MIC Creep" Phenomenon. Acta Med Indones. 2019 Jan;51(1):10-18.

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• Leon C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F, Garnacho-Montero J, Leon MA; EPCAN Study Group. A bedside scoring system ("Candida score") for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med. 2006 Mar;34(3):730-7. doi: 10.1097/01.CCM.0000202208.37364.7D.

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  PMID: 24978045 RESULT

• Yahav D, Lador A, Paul M, Leibovici L. Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother. 2011 Sep;66(9):1963-71. doi: 10.1093/jac/dkr242. Epub 2011 Jun 18.

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Related Links

• Karaiskos I, Barmpouti E, Ioannidis K, et al. Hypofibrinogenaemia associated with the administration of tigecycline. Conference Paper (poster). Conference: 24th ECCMID; 2014, Barcelona, Spain. doi: 10.13140/2.1.2337.2163.

Biospecimen

Retention: SAMPLES WITH DNA

Genotyping will be performed using the modification option of VeriDose® Core Panel (VeriDose and Agena Bioscience are registered trademarks of Agena Bioscience, Inc.). VeriDose® Core Panel provides the detection of the most relevant variants in the key genes involved in drug metabolism pathways: Pg-s gene ABCB1, APOE, CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5, DRD2, F2, F5, GLP1R, MTHFR, OPRM1, PNPLA5, SLCO1B1, SULT4A1, VKORC1.

MeSH Terms

Interventions

Pharmacogenomic Testing

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Anna Vlasova, PhD, MD

  Morozov Children's City Clinical Hospital of the Moscow City Health Department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD, chief of Clinical Pharmacology department

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 28, 2019
• Study Start: February 1, 2020
• Primary Completion: August 28, 2021
• Study Completion: October 15, 2021
• Last Updated: March 18, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Data will be available within 6 months of study completion.
• Access Criteria: Data Access Requests will be reviewed by the Independent Local Review Board. Requestors will be required to sign a Data Access Agreement.

Locations

RU (1)