Clinical trial NCT04004078: An Individualized Administration Research of Voriconazole Based on CYP2C19 Gene Polymorphism and TDM
Official title: An Individualized Administration Research of Voriconazole Based on CYP2C19 Gene Polymorphism and Therapeutic Drug Monitoring in Chinese Patients With Invasive Pulmonary Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Invasive Fungal Infection
Lead sponsor: People's Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2019-07-01
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All voriconazole-treated adult Chinese patients with invasive pulmonary infection were admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from March 2018 to April 2020.

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 March 2018 to April 2020.

Detailed description: 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 March 2018 to April 2020. Patients were included who met the following criteria:(1)age≥18 years old, (2)Diagnosis of invasive fungal infection,(3)written informed consent was obtained from each patients,(4)At least one steady trough concentration blood sample was taken from each patient.

Patients were excluded who fulfilled any of the following criteria:(1) patients who are allergic to voriconazole or have poor compliance, (2) use other antifungal drugs during the use of VCZ, (3) do not qualify for blood sampling monitored by blood concentration, (4) patients with severe liver function impairment (ALT and AST before VCZ treatment are greater than 5 times the normal upper limit, TBIL is greater than 3 times the normal upper limit), 5) pregnant or lactating women, (6) with incomplete clinical data collection, (7) have participated in other clinical trials in the past three months.

Grouping: 1) The patients were grouped according to CYP2C19 gene detection, they were divided into gene-directed group and non-gene-directed group; 2) According to the effect of treatment, the patients were divided into effective group and ineffective group; 3) According to whether patients had adverse reactions, they were divided into group A (adverse reactions) and group B (no adverse reactions). The clinical indicators and detection values of each group were recorded, respectively.

Loading Dosage of administration and treatment regimen : All the selected patients were treated with VCZ. Dose of administration is shown for gene-directed group and non-gene-directed group below. The maintenance dosage was increased or decreased appropriately up to target Cmin range (0.5μg/ml\~5.0μg/ml).

According to CYP2C19 gene detection, phenotypes were classified as ultrarapid metabolisers(UMs)，extensive metabolisers(EMs) ，intermediate metabolisers(IMs) and poor metabolisers(PMs).

Dose of administration and treatment regimen according to CYP2C19 gene detection:(1)Non- gene directed group：Voriconazole was intravenously administered 2 times at the loading dose of 6mg/Kg at 12h intervals , followed by maintenance dosing 4mg/Kg at 12h intervals . Voriconazole was oral administered 2 times at the loading dose of 400mg or 200mg（weight\>40Kg or \<40Kg）at 12h intervals , followed by maintenance dosing 200mg or 100mg（weight\>40Kg or \<40Kg）. Voriconazole was sequential therapy administered 2 times at the loading dose of 6mg/Kg at 12h intervals , followed by maintenance dosing 200mg or 100mg（weight\>40Kg or \<40Kg）. (2) Gene directed group: The dosage of the drug was the same as that of the non-gene-directed group for patients with UMs，EMs and IMs. For the patients with PMs，Voriconazole was intravenously administered 2 times at the loading dose of 4mg/Kg at 12h intervals , followed by maintenance dosing 3mg/Kg at 12h intervals . Voriconazole was oral administered 2 times at the loading dose of 200mg or 100mg（weight\>40Kg or \<40Kg） at 12h intervals , followed by maintenance dosing 100mg . Voriconazole was sequential therapy administered 2 times at the loading dose of 4mg/Kg at 12h intervals , followed by maintenance dosing 100mg.

Eligibility criteria: Inclusion Criteria:

* age≥18 years old
* Diagnosis of invasive fungal infection
* written informed consent was obtained from each patients
* At least one steady trough concentration blood sample was taken from each patient

Exclusion Criteria:

* patients who are allergic to voriconazole or have poor compliance
* use other antifungal drugs during the use of VCZ
* do not qualify for blood sampling monitored by blood concentration
* patients with severe liver function impairment (ALT and AST before VCZ treatment are greater than 5 times the normal upper limit, TBIL is greater than 3 times the normal upper limit)
* pregnant or lactating women,
* with incomplete clinical data collection
* have participated in other clinical trials in the past three months

Primary outcomes:
measure: Serum voriconazole trough concentrations
timeFrame: 0.5 hour before voriconazole administration on the Thirdth or sixth day
Secondary outcomes:
measure: The difference of average Cmin among group A, group B, group C and group D
timeFrame: From March 2018 to April 2020
measure: The correlation between Cmin and CRP, IL-6 and PCT
timeFrame: From March 2018 to April 2020
measure: The effect of voriconazole on liver injury biomarkers
timeFrame: From March 2018 to April 2020
measure: Determination of Predictors of voriconazole Cmin
timeFrame: From March 2018 to April 2020
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Zhengzhou Central Hospital affiliated to Zhengzhou University
state: Henan
Study officials:
References: