UnknownNot Applicable

Influence of CYP2C19 Genotype on Safety and Efficacy of Voriconazole in Pediatric Patients With Hematologic Malignancy

Turkey (Türkiye)62 participantsStarted 2019-11-01

Plain-language summary

Voriconazole is a drug used to treat invasive fungal infections. The amount of voriconazole in a person's blood helps to determine how effectively it treats an infection, and how safe it is. Patients respond differently when receiving the same dose - some clearly benefit, other patients experience side effects, and others see limited improvement in their infection. Voriconazole is broken down in the liver mainly by an enzyme called CYP2C19, before being excreted from the body. The activity of CY2C19 differs between people because of variation in the DNA that encodes the body's instructions to make CYP2C19. If CYP2C19 activity is very high, voriconazole blood levels may remain below the target range when a patient receives a standard dose of voriconazole, which may be insufficient to treat their infection. Besides, children tend to have faster voriconazole metabolism regardless of the genetic makeup, mainly because of higher liver mass/body proportion. That's why, younger patients needs higher doses and it is harder for them to reach target range. Having a high CYP2C19 activity and being young combined may cause to consider choosing an alternative drug. By contrast, decreased CYP2C19 activity due to genetic variation may result in excessively high voriconazole blood levels, predisposing to serious side effects. Therefore, knowing a patient's CYP2C19 genetic makeup is very important for predicting their response to voriconazole. Thus, we aim to determine the influence of genetic variation in CYP2C19 on the frequency and severity of side effects related to voriconazole, and on the effectiveness of voriconazole for treating serious fungal infections. The findings from this study will contribute to determining the optimal dose of voriconazole that patients with different genetic variants in CYP2C19 should be started on, and will take us one step closer to both understanding the genetic structure of CYP2C19 in the Turkish population, and to 'personalised medicine'.

Who can participate

Age range

2 Years – 18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Aged between ≥2 years and \<18 years * Receiving voriconazole for the treatment of an invasive fungal infection (IFI) and are within the first five days of the treatment course, OR are receiving voriconazole for the secondary prophylaxis against IFI during or after chemotherapy * Agree to give one additional blood sample twice during the study for the purposes of pharmacogenetic analysis and determination of the serum trough voriconazole concentration, whilst their blood is being collected during normal clinical follow up without the requirement for any additional intravenous intervention * Are willing and able to give informed consent and sign the informed consent form (by the patients and the parents OR the legal guardians) Exclusion Criteria: * Have previously had CYP2C19 PGx testing performed * Pregnant/breastfeeding * Have cognitive impairment and/or psychiatric disorders and/or any other condition that will draw into question their capacity to provide informed consent * Have severe hepatic insufficiency (Child-Pugh Class C) and have renal failure (estimated GFR \<15ml/min /1,73m2)

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

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Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Frequency and severity of voriconazole related adverse drug reactions

Timeframe: Follow up period for primary outcome is 30 days for each participant

Trial details

NCT IDNCT04743544

SponsorDokuz Eylul University

Sponsor typeOTHER

Study typeOBSERVATIONAL

Primary completion2021-12-31

Contact for this trial

Mukaddes Gumustekin, Professor, MD, PhD

+902324123906 gumustekinm@gmail.com

View on ClinicalTrials.gov More Adverse Drug Reactions trials