Factors on Therapeutic Drug Monitoring and Safety of Voriconazole in Critically Ill Elderly Patients

NCT06137690 | Recruiting DMC FDA Device

• 1 other identifier: LJzhou
• Study Type: observational
• Target: 550
• 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 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.

Conditions

Invasive Fungal Infection

Outcome Measures

Primary Outcomes (4)

• 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.

  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).

  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.

  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.

  From July 2018 to June 2023

Secondary Outcomes (8)

• C-reaction protein (CRP)

  Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy

• Alanine aminotransferase (ALT)

  Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy

• Aspartatrtransaminase (AST)

  Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy

• Gamma-glutamyl transferase(GGT)

  Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy

• Alkaline phosphatase (ALP)

  Before initiation, On the day of blood sample extraction with serum trough concentration, and completion of voriconazole therapy

Study Arms (2)

Group A

the elderly group , the age ≥ 60 years

Device: other antifungal agents,breathing machine

Group B

the non-elderly group , the age \< 60 years

Device: other antifungal agents,breathing machine

Interventions

other antifungal agents,breathing machine DEVICE

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.

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 98 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 Henan Chinese Han patients with invasive pulmonary infection were admitted to Zhengzhou Central Hospital affiliated to Zhengzhou University from July 2018 to June 2023.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• People's Hospital of Zhengzhou University: lead

Study Sites (1)

Zhengzhou Central Hospital affiliated to Zhengzhou University

Zhengzhou, Henan, 41, China

RECRUITING

MeSH Terms

Conditions

Invasive Fungal Infections

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Central Study Contacts

Zhou Li-juan Zhou Li-juan, master

CONTACT

13838014946; zhou750423@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 18, 2023
• Study Start: July 1, 2018
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: February 16, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)