An Individualized Administration Research of Voriconazole Based on CYP2C19 Gene Polymorphism and TDM

NCT04004078 | Completed DMC FDA Device

• 1 other identifier: zhou750423
• Study Type: observational
• Target: 314
• Locations: 1 country
• Sites: 1

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.

Conditions

Invasive Fungal Infection

Outcome Measures

Primary Outcomes (1)

• 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 (Cmin) were determined by a high-performance liquid chromatography method as previously described. The detections were completed in Translational Medicine Center of Zhengzhou Central Hospital affiliated to Zhengzhou University.

  0.5 hour before voriconazole administration on the Thirdth or sixth day

Secondary Outcomes (4)

• The difference of average Cmin among group A, group B, group C and group D

  From March 2018 to April 2020

• The correlation between Cmin and CRP, IL-6 and PCT

  From March 2018 to April 2020

• The effect of voriconazole on liver injury biomarkers

  From March 2018 to April 2020

• Determination of Predictors of voriconazole Cmin

  From March 2018 to April 2020

Study Arms (4)

Group A

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）.

Device: other antifungal agents,breathing machine

Group B

Gene directed group（UMs and EMs）：The dosage of the drug was the same as that of the non-gene-directed group for patients with UMs，EMs.

Device: other antifungal agents,breathing machine

Group C

Gene directed group（IMs）：The dosage of the drug was the same as that of the non-gene-directed group for patients with IMs.

Device: other antifungal agents,breathing machine

Group D

Gene directed group（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.

Device: other antifungal agents,breathing machine

Interventions

other antifungal agents,breathing machine DEVICE

If treatment failure for patients in group A，group B，group C and group D，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.

Group A; Group B; Group C; Group D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• People's Hospital of Zhengzhou University: lead

Study Sites (1)

Zhengzhou Central Hospital affiliated to Zhengzhou University

Zhengzhou, Henan, 41, China

Location

MeSH Terms

Conditions

Invasive Fungal Infections

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: July 1, 2019
• Study Start: March 1, 2018
• Primary Completion: April 30, 2021
• Study Completion: May 1, 2021
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)