Invasive Fungal InfectionNCT04004078
An Individualized Administration Research of Voriconazole Based on CYP2C19 Gene Polymorphism and TDM
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 March 2018 to April 2020. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Fungal Infection
- What is being tested?
- other antifungal agents,breathing machine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- How many people
- 314 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2018to 1 May 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Zhengzhou Central Hospital affiliated to Zhengzhou University
Zhengzhou, Henan, 41
About this study
Official title: An Individualized Administration Research of Voriconazole Based on CYP2C19 Gene Polymorphism and Therapeutic Drug Monitoring in Chinese Patients With Invasive Pulmonary Infection
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.
Read the 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.
- 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，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.
| Study group | Role | What they receive |
|---|---|---|
| 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）. Receives: 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. Receives: 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. Receives: 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. 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 (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.
Measured: 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
The differences were counted among group A, group B, group C and group D by measuring each person's Cmin.
Measured: From March 2018 to April 2020
The correlation between Cmin and CRP, IL-6 and PCT
The correlation between Cmin and CRP, IL-6 and PCT by Pear's correlation analysis .CRP,IL-6 and PCT were completed before initiation ,after voriconazole therapy on day 3,7 and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: From March 2018 to April 2020
The effect of voriconazole on liver injury biomarkers
The effects of different level of voriconazole-Cmin (<0.5,0.5-5,and>5μg/ml ) on liver injury biomarkers( ALT,AST,ALP and GGT ).The differences among 3groups were compared using one-way analysis of variance /post(Scheffe) test.They were determined before initiation ,after voriconazole therapy on day 3,7 and completion of voriconazole therapy in Zhengzhou city clinical inspection center.
Measured: From March 2018 to April 2020
Determination of Predictors of voriconazole Cmin
The voriconazole Cmin variation may be influenced by many factors. A backward multiple linear regression model was performed for determination of predictors of voriconazole Cmin.
Measured: From March 2018 to April 2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2019
- Study start1 Mar 2018
- Primary completion30 Apr 2021
- Study completion1 May 2021
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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 314 participants (actual)
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
- NCT04004078
- Sponsor's protocol ID
- zhou750423
- Status last verified
- Apr 2022
- First submitted
- 26 Jun 2019
- Last updated
- 20 Apr 2022
- 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 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Individualized Administration Research of Voriconazole Based on CYP2C19 Gene Polymorphism and Therapeutic Drug Monitoring in Chinese Patients With Invasive Pulmonary Infection
- ClinicalTrials.gov ID
- NCT04004078
- Acronym / sponsor ID
- zhou750423
- Conditions
- Invasive Fungal Infection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 314 participants (actual)
- Lead sponsor
- People's Hospital of Zhengzhou UniversityUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 1 May 2021 (actual)
- First posted
- 1 Jul 2019 (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 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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Device: other antifungal agents,breathing machineNon-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）. |
| Group B | – | Device: other antifungal agents,breathing machineGene 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. |
| Group C | – | Device: other antifungal agents,breathing machineGene directed group（IMs）：The dosage of the drug was the same as that of the non-gene-directed group for patients with IMs. |
| Group D | – | Device: other antifungal agents,breathing machineGene 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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,
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，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. | Device | Group A, Group B, Group C, Group D |
Primary outcome
Serum voriconazole trough concentrations
Time frame: 0.5 hour before voriconazole administration on the Thirdth 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 (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.
4 secondary outcomes
The difference of average Cmin among group A, group B, group C and group D
Time frame: From March 2018 to April 2020
The correlation between Cmin and CRP, IL-6 and PCT
Time frame: From March 2018 to April 2020
The effect of voriconazole on liver injury biomarkers
Time frame: From March 2018 to April 2020
Determination of Predictors of voriconazole Cmin
Time frame: From March 2018 to April 2020
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2022.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 4 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: finished, as of the sponsor's last update on 20 Apr 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. 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 Thirdth or sixth day). 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 20 Apr 2022.