Invasive Fungal InfectionNCT06137690
Factors on Therapeutic Drug Monitoring and Safety of Voriconazole in Critically Ill Elderly Patients
An observational study of Invasive Fungal Infection, run by People's Hospital of Zhengzhou University at 1 site in China.
Trial summary
This was a prospective clinical study that all voriconazole-treated adult Chinese patients with invasive pulmonary infection admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from July 2018 to June 2023. Read more about this study
- Who is it for?
- Ages 18 to 98 years
- Conditions the study is for
- Invasive Fungal Infection
- What is being tested?
- other antifungal agents,breathing machine
- Type of treatment
- Injection or infusion, Medical device
- How many people
- 550 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2018to 1 Mar 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 98 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All voriconazole-treated adult Henan Chinese Han patients with invasive pulmonary infection were admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from July 2018 to June 2023.
Who may be able to join
- patients who met the criteria for diagnosis of IFI
- age ≥ 18 years
- The duration of VCZ treatment course ≥ 7 days.
Who cannot join
- Patients who allergic to VCZ
- use other anti-fungal drugs during the use of VCZ
- do not qualify for blood sampling monitored by blood concentration
- pregnant or lactating women
- patients who haven't completely and accurately efficacy and safety data
- patients who are treated with a combination of liver enzyme inducers and inhibitors(carbamazepine, phenobarbital, phenytoin, cimetidine, rifampin, rifapentine, rifabutin, and so on)
- patients who are treated with a combination of Paxlovid or Azvudine.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhengzhou Central Hospital affiliated to Zhengzhou University
Zhengzhou, Henan, 41
Zhou Li-juan Zhou Li-juan, master, 13838014946, zhou750423@126.com
About this study
Official title: Factors on Therapeutic Drug Monitoring and Safety of Voriconazole in Critically Ill Elderly Patients: A Prospective Observational Study
This was a prospective clinical study that all voriconazole-treated adult Chinese patients with invasive pulmonary infection admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from July 2018 to June 2023. The initial voriconazole serum trough concentration, Correlation of various factors, and risk prediction factors for voriconazole serum trough concentration and hepatotoxicity were compared between elderly and non-elderly patients.
Read the detailed description
A prospective observational study was conducted from July 2018 to June 2023 in Zhengzhou Central Hospital Affiliated to Zhengzhou University. This study was carried out in accordance with the following criteria: (1) patients who met the criteria for diagnosis of IFI, (2) age ≥ 18 years, (3) The duration of VCZ treatment course ≥ 7 days.
Patients were excluded who fulfilled any of the following criteria: (1) Patients who allergic to VCZ, (2) use other anti-fungal drugs during the use of VCZ, (3) do not qualify for blood sampling monitored by blood concentration, (4) pregnant or lactating women, (5) patients who haven't completely and accurately efficacy and safety data, (6) patients who are treated with a combination of liver enzyme inducers and inhibitors (carbamazepine, phenobarbital, phenytoin, cimetidine, rifampin, rifapentine, rifabutin, and so on),(7) patients who are treated with a combination of Paxlovid or Azvudine.
Grouping: Patients were divided into the elderly group (group A, ≥ 60 years) and the non-elderly group (group B, < 60 years) according to ages. All the recruited patients were treated with voriconazole. Voriconazole was intravenously administered 2 times at the loading dose of 6 mg/Kg or orally administered 2 times at the loading dose of 400mg at 12h intervals, followed by a maintenance dose of 4 mg/Kg or 200 mg at 12 h intervals.
- Conditions
- Invasive Fungal Infection
- Being tested
- other antifungal agents,breathing machine
- Medical subject headings
- Invasive Fungal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
other antifungal agents,breathing machineDevice
If treatment failure for patients in group A and group B，change other antifungal agents (Amphotericin B for Injection, 25mg, North China Pharmaceutical Co., Ltd or Caspofungin Acetate for lnjection,50mg and 70mg Cancidas®). Mechanical ventilation (EVITA 4, Dräger Medical Equipment (Shanghai) Co.,Ltd) was adopte.Treatment failure was defined as no improvement or worse of clinical symptoms, laboratory data, requiring change of antifungal agents therapy.
| Study group | Role | What they receive |
|---|---|---|
| Group A | the elderly group , the age ≥ 60 years Receives: Device: other antifungal agents,breathing machine | |
| Group B | the non-elderly group , the age < 60 years Receives: Device: other antifungal agents,breathing machine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum voriconazole trough concentrations
If all patients were administrated by loading dose, voriconazole trough samples were taken immediately 30 minutes before voriconazole administration on the Third day. If all patients were not administrated by loading dose, voriconazole trough samples were taken immediately 30 minutes before voriconazole administration on the sixth day. Blood samples for 2-3 mL were collected in blood-collection tubes without any additives and centrifuged at 3500 rpm for 10min. Serum trough concentrations were determined by a high-performance liquid chromatography method as previously described. A initial steady-state trough concentration blood sample was obtained before dose adjustment for all patients. Each patient received at least one steady-state blood sample. The detections were completed in Translational Medicine Center of Zhengzhou Central Hospital affiliated to Zhengzhou University.
Measured: 0.5 hour before voriconazole administration on the Third or sixth day.
CYP2C19 Genotyping
CYP2C19 genotype was determined from peripheral blood, which was extracted and stored in an EDTA anticoagulant tube. Real-time fluorescence quantitative PCR (ThermoFisher Applied Biosystems 7500 fast PCR) was performed using a Human CYP2C19 gene detection kit (PCR-fluorescence probe method, Wuhan YZY Medical Science and Technology Co., Ltd, China) following the manufacturer's instructions. Genomic DNA was isolated from whole blood using QIAamp DNA blood kits (Qiagen, Hilden, Germany). According to nomenclature by the Clinical Pharmacogenetics Implementation Consortium (CPIC®), the CYP2C19 genotype was classified as ultrarapid metabolizer (*17/*17), rapid metabolizer (*1/*17), normal metabolizer (*1/*1), intermediate metabolizer (*1/*2, *1/*3, *2/*17, *3/*17), or poor metabolizer (*2/*2, *2/*3, *3/*3).
Measured: Unlimited blood drawing time.
The difference of average voriconazole serum trough concentration between group A and group B
The differences were counted between group A and group B by measuring each patient's voriconazole serum trough concentration.
Measured: From July 2018 to June 2023
Analysis of factors affecting voriconazole serum trough concentration
A multiple linear stepwise regression analysis was performed by using voriconazole serum trough concentration (Y) as the dependent variable, and sex (x1), age (x2), body weight (x3), VCZ route of administration (x4), CYP2C19 phenotype (x5), the average daily dose (x6), PPIs (x7), methylprednisolone (x8), CRP (x9) , PCT (x10), IL-6 (x11), Albumin (x12), ALP (x13), and TBIL (x14) as independent variables. Linear regression analysis reveals the regression equation and independent risk factors affecting voriconazole serum trough concentration.
Measured: From July 2018 to June 2023
Secondary outcomes (8)
C-reaction protein (CRP)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Alanine aminotransferase (ALT)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Aspartatrtransaminase (AST)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Gamma-glutamyl transferase(GGT)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Alkaline phosphatase (ALP)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Total bilirubin (TBIL)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
procalcitonin(PCT)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
interleukin- 6(IL-6)
It was completed before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start1 Jul 2018
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invasive Fungal InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 550 participants (estimated)
Sponsor and investigators
- Lead sponsor
- People's Hospital of Zhengzhou University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, LIjuan Zhou, People's Hospital of Zhengzhou University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06137690
- Sponsor's protocol ID
- LJzhou
- Status last verified
- Feb 2024
- First submitted
- 14 Nov 2023
- Last updated
- 16 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Factors on Therapeutic Drug Monitoring and Safety of Voriconazole in Critically Ill Elderly Patients: A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT06137690
- Acronym / sponsor ID
- LJzhou
- Conditions
- Invasive Fungal Infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 550 participants (estimated)
- Lead sponsor
- People's Hospital of Zhengzhou UniversityUniversity, hospital or other
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2024 (estimated)
- First posted
- 18 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a prospective clinical study that all voriconazole-treated adult Chinese patients with invasive pulmonary infection admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from July 2018 to June 2023. The initial voriconazole serum trough concentration, Correlation of various factors, and risk prediction factors for voriconazole serum trough concentration and hepatotoxicity were compared between elderly and non-elderly patients.
Detailed description
A prospective observational study was conducted from July 2018 to June 2023 in Zhengzhou Central Hospital Affiliated to Zhengzhou University. This study was carried out in accordance with the following criteria: (1) patients who met the criteria for diagnosis of IFI, (2) age ≥ 18 years, (3) The duration of VCZ treatment course ≥ 7 days.
Patients were excluded who fulfilled any of the following criteria: (1) Patients who allergic to VCZ, (2) use other anti-fungal drugs during the use of VCZ, (3) do not qualify for blood sampling monitored by blood concentration, (4) pregnant or lactating women, (5) patients who haven't completely and accurately efficacy and safety data, (6) patients who are treated with a combination of liver enzyme inducers and inhibitors (carbamazepine, phenobarbital, phenytoin, cimetidine, rifampin, rifapentine, rifabutin, and so on),(7) patients who are treated with a combination of Paxlovid or Azvudine.
Grouping: Patients were divided into the elderly group (group A, ≥ 60 years) and the non-elderly group (group B, < 60 years) according to ages. All the recruited patients were treated with voriconazole. Voriconazole was intravenously administered 2 times at the loading dose of 6 mg/Kg or orally administered 2 times at the loading dose of 400mg at 12h intervals, followed by a maintenance dose of 4 mg/Kg or 200 mg at 12 h intervals.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Device: other antifungal agents,breathing machinethe elderly group , the age ≥ 60 years |
| Group B | – | Device: other antifungal agents,breathing machinethe non-elderly group , the age < 60 years |
Who may qualify
- Ages
- 18 to 98 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All voriconazole-treated adult Henan Chinese Han patients with invasive pulmonary infection were admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from July 2018 to June 2023.
Key inclusion criteria (3 listed)
- patients who met the criteria for diagnosis of IFI
- age ≥ 18 years
- The duration of VCZ treatment course ≥ 7 days.
Key exclusion criteria (7 listed)
- Patients who allergic to VCZ
- use other anti-fungal drugs during the use of VCZ
- do not qualify for blood sampling monitored by blood concentration
- pregnant or lactating women
- patients who haven't completely and accurately efficacy and safety data
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| other antifungal agents,breathing machineIf treatment failure for patients in group A and group B，change other antifungal agents (Amphotericin B for Injection, 25mg, North China Pharmaceutical Co., Ltd or Caspofungin Acetate for lnjection,50mg and 70mg Cancidas®). Mechanical ventilation (EVITA 4, Dräger Medical Equipment (Shanghai) Co.,Ltd) was adopte.Treatment failure was defined as no improvement or worse of clinical symptoms, laboratory data, requiring change of antifungal agents therapy. | Device | Group A, Group B |
Primary outcome
Serum voriconazole trough concentrations
Time frame: 0.5 hour before voriconazole administration on the Third or sixth day.
If all patients were administrated by loading dose, voriconazole trough samples were taken immediately 30 minutes before voriconazole administration on the Third day. If all patients were not administrated by loading dose, voriconazole trough samples were taken immediately 30 minutes before voriconazole administration on the sixth day. Blood samples for 2-3 mL were collected in blood-collection tubes without any additives and centrifuged at 3500 rpm for 10min. Serum trough concentrations were determined by a high-performance liquid chromatography method as previously described. A initial steady-state trough concentration blood sample was obtained before dose adjustment for all patients. Each patient received at least one steady-state blood sample. The detections were completed in Translational Medicine Center of Zhengzhou Central Hospital affiliated to Zhengzhou University.
CYP2C19 Genotyping
Time frame: Unlimited blood drawing time.
CYP2C19 genotype was determined from peripheral blood, which was extracted and stored in an EDTA anticoagulant tube. Real-time fluorescence quantitative PCR (ThermoFisher Applied Biosystems 7500 fast PCR) was performed using a Human CYP2C19 gene detection kit (PCR-fluorescence probe method, Wuhan YZY Medical Science and Technology Co., Ltd, China) following the manufacturer's instructions. Genomic DNA was isolated from whole blood using QIAamp DNA blood kits (Qiagen, Hilden, Germany). According to nomenclature by the Clinical Pharmacogenetics Implementation Consortium (CPIC®), the CYP2C19 genotype was classified as ultrarapid metabolizer (*17/*17), rapid metabolizer (*1/*17), normal metabolizer (*1/*1), intermediate metabolizer (*1/*2, *1/*3, *2/*17, *3/*17), or poor metabolizer (*2/*2, *2/*3, *3/*3).
The difference of average voriconazole serum trough concentration between group A and group B
Time frame: From July 2018 to June 2023
The differences were counted between group A and group B by measuring each patient's voriconazole serum trough concentration.
Analysis of factors affecting voriconazole serum trough concentration
Time frame: From July 2018 to June 2023
A multiple linear stepwise regression analysis was performed by using voriconazole serum trough concentration (Y) as the dependent variable, and sex (x1), age (x2), body weight (x3), VCZ route of administration (x4), CYP2C19 phenotype (x5), the average daily dose (x6), PPIs (x7), methylprednisolone (x8), CRP (x9) , PCT (x10), IL-6 (x11), Albumin (x12), ALP (x13), and TBIL (x14) as independent variables. Linear regression analysis reveals the regression equation and independent risk factors affecting voriconazole serum trough concentration.
8 secondary outcomes
C-reaction protein (CRP)
Time frame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Alanine aminotransferase (ALT)
Time frame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Aspartatrtransaminase (AST)
Time frame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Gamma-glutamyl transferase(GGT)
Time frame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Alkaline phosphatase (ALP)
Time frame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Total bilirubin (TBIL)
Time frame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
procalcitonin(PCT)
Time frame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
interleukin- 6(IL-6)
Time frame: before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Invasive Fungal Infection, run by People's Hospital of Zhengzhou University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhou Li-juan Zhou Li-juan, master (13838014946, zhou750423@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum voriconazole trough concentrations (time frame: 0.5 hour before voriconazole administration on the Third or sixth day.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2024.