Clinical trial NCT06137690: Factors on Therapeutic Drug Monitoring and Safety of Voriconazole in Critically Ill Elderly Patients
Official title: Factors on Therapeutic Drug Monitoring and Safety of Voriconazole in Critically Ill Elderly Patients: A Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Invasive Fungal Infection
Lead sponsor: People's Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Maximum age (years): 98
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* patients who met the criteria for diagnosis of IFI
* age ≥ 18 years
* The duration of VCZ treatment course ≥ 7 days.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Serum voriconazole trough concentrations
timeFrame: 0.5 hour before voriconazole administration on the Third or sixth day.
measure: CYP2C19 Genotyping
timeFrame: Unlimited blood drawing time.
measure: The difference of average voriconazole serum trough concentration between group A and group B
timeFrame: From July 2018 to June 2023
measure: Analysis of factors affecting voriconazole serum trough concentration
timeFrame: From July 2018 to June 2023
Secondary outcomes:
measure: C-reaction protein (CRP)
timeFrame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
measure: Alanine aminotransferase (ALT)
timeFrame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
measure: Aspartatrtransaminase (AST)
timeFrame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
measure: Gamma-glutamyl transferase(GGT)
timeFrame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
measure: Alkaline phosphatase (ALP)
timeFrame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
measure: Total bilirubin (TBIL)
timeFrame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
measure: procalcitonin(PCT)
timeFrame: Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
measure: interleukin- 6(IL-6)
timeFrame: before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Zhengzhou Central Hospital affiliated to Zhengzhou University
state: Henan
Study officials:
References: