Invasive Pulmonary AspergillosisNCT02100761
CYP 2C19 Polymorphism and Voriconazole Trough Concentration in Chinese Adult Patients
An observational study of Invasive Pulmonary Aspergillosis, run by dingshifang at 1 site in China.
Trial summary
To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and the steady-state blood concentration of voriconazole in Chinese patients with invasive pulmonary aspergillosis (IPA), and to assess the effects of voriconazole trough concentration on the prognosis of IPA patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Invasive Pulmonary Aspergillosis
- What is being tested?
- Voriconazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- Jun 2014to Jun 2015
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision
Who may be able to join
- Proven, probable, or possible invasive pulmonary aspergillosis (IPA)
- Acute IPA defined as duration of clinical syndrome of <30 days.
- Treatment with voriconazole
- At least 18 years and older
- Weight >40 kg and ≤120 kg
- Given the informed consent
Who cannot join
- Patients allergic to azole(s)
- Patients who heve been prescribed voriconazole before
- Positive urine pregnancy test (if female)
- Patients with aspergilloma or chronic aspergillosis ( >1 month duration )
- Anticipated survival of less than 5 days or Karnofsky score <=20
Trial locations and contacts
1 site in 1 country.
China1 site
Qilu Hospital
Jinan, Shandong, 250012
Shifang Ding, Ph.D., 18560081003 ext. +86, dingshifang@sdu.edu.cn
Shifang Ding, Ph.D.
About this study
Official title: Impact of Cytochrome P450 2C19 Genotype Polymorphism on Voriconazole Trough Concentration in Chinese Adult Patients With Invasive Pulmonary Aspergillosis: a Prospective Multicenter Research
To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and the steady-state blood concentration of voriconazole in Chinese patients with invasive pulmonary aspergillosis (IPA), and to assess the effects of voriconazole trough concentration on the prognosis of IPA patients.
Read the detailed description
Each isolate of aspergillosis will be recovered from clinical specimens (sputum, bronchoalveolar lavage fluid, lung biopsy tissue) and the identification of species level will also be performed in Qilu Hospital by using conventional methods (both macroscopic and microscopic characteristics). The aspergillosis strains will be stored in 10 % glycerol broth at -80 °C. The in vitro antifungal susceptibility test of aspergillosis strains to voriconazole will be performed in the Centre for Medical Mycology and Mycoses, First Hospital, Peking University, and the performance will be according to the Clinical and Laboratory Standards Institute (CLSI) standard M38-A2 microdilution methods.
Serum galactomannan (GM) test will be performed twice per week for the first two weeks. A double-sandwich ELISA GM assay was used. A cut-off of optical density index (ODI) >0.5 was taken as positive.
Voriconazole serum levels will be measured on day 4, day 7, day 10, and day 14 (all trough levels). In brief, quantitative analysis of voriconazole was performed using high-performance liquid chromatography coupled with tandem mass spectrometry.
Genotyping of CYP2C19 will be performed using 3 ml of peripheral blood sampled into EDTA (ethylenediaminetetraacetic acid) tubes at day 4. Genomic DNA was extracted from blood leukocytes with the use of a DNA extraction kit. Genotyping was confirmed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. Individuals can be divided into three groups according to the CYP2C19 genotype. Those who inherit two mutant CYP2C19 alleles (*2 and/or *3) have a reduced capacity to metabolize CYP2C19 substrates and are defined as poor metabolizers (PMs). Individuals who are homozygous (*1/*1) for wild-type CYP2C19*1 or 1 wild-type allele and 1 CY¬P2C19*17 have efficient enzymes to metabolize CYP2C19 substrates and are defined as extensive metabolizers (EMs). Subjects who are heterozygous (*1/*2, *1/*3) for wild-type CYP2C19*1 are defined as intermediate metabolizers (IMs)
- Conditions
- Invasive Pulmonary Aspergillosis
- Being tested
- Voriconazole
- Keywords
- Voriconazole, Invasive pulmonary aspergillosis, Therapeutic drug monitoring, CYP genetic polymorphism, Efficacy, Safety
- Medical subject headings
- Invasive Pulmonary Aspergillosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VoriconazoleDrug
Also called Voriconazole Intravenous Solution 200 mg, Voriconazole Tablet 50 mg / Voriconazole Tablet 200 mg
Patients with creatinine clearance at least 50 ml/min will be treated with voriconazole by intravenous drip infusion at the dose of 6 mg/kg twice daily on the first day (Day 1) and 4 mg/kg twice daily from day 2 onward. The IV treatment is at least 7 days. Then switch to 200 mg orally twice daily between meals. The total treatment duration is at least 14 days Patients with creatinine clearance <50 ml/min will be treated with oral voriconazole (loading dose of 400 mg twice daily followed by maintenance dose of 200 mg twice daily between meals for at least 14.0 days).
| Study group | Role | What they receive |
|---|---|---|
| invasive pulmonary aspergillosis | Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision in five hospital, Jinan, China Receives: Drug: Voriconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
voriconazole trough level
Measured: one year
Secondary outcomes (1)
Overall mortality
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2014 (estimated)
- Study startJun 2014
- Primary completionJun 2015 (estimated)
- Study completionJun 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invasive Pulmonary AspergillosisStudies 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 only
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- dingshifang
- Sponsor type
- University, hospital or other
- Collaborators
- Shandong Provincial Hospital, Qianfoshan Hospital, Shandong thorax hospital, Jinan Military General Hospital, Jinan Central Hospital
- Responsible party
- Sponsor-investigator, dingshifang, Qilu Hospital of Shandong University
- Investigators
- Shifang Ding, Ph.D., Study chair, Qilu Hospital of Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100761
- Sponsor's protocol ID
- KYLL-2014(KS)-085
- Status last verified
- Mar 2014
- First submitted
- 3 Mar 2014
- Last updated
- 1 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Cytochrome P450 2C19 Genotype Polymorphism on Voriconazole Trough Concentration in Chinese Adult Patients With Invasive Pulmonary Aspergillosis: a Prospective Multicenter Research
- ClinicalTrials.gov ID
- NCT02100761
- Acronym / sponsor ID
- KYLL-2014(KS)-085
- Conditions
- Invasive Pulmonary Aspergillosis
- Keywords
- Voriconazole, Invasive pulmonary aspergillosis, Therapeutic drug monitoring, CYP genetic polymorphism, Efficacy, Safety
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- dingshifangUniversity, hospital or other
- Collaborators
- Shandong Provincial Hospital, Qianfoshan Hospital, Shandong thorax hospital, Jinan Military General Hospital, Jinan Central Hospital
- Study start
- Jun 2014
- Primary completion
- Jun 2015 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 1 Apr 2014 (estimated)
- 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.
To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and the steady-state blood concentration of voriconazole in Chinese patients with invasive pulmonary aspergillosis (IPA), and to assess the effects of voriconazole trough concentration on the prognosis of IPA patients.
Detailed description
Each isolate of aspergillosis will be recovered from clinical specimens (sputum, bronchoalveolar lavage fluid, lung biopsy tissue) and the identification of species level will also be performed in Qilu Hospital by using conventional methods (both macroscopic and microscopic characteristics). The aspergillosis strains will be stored in 10 % glycerol broth at -80 °C. The in vitro antifungal susceptibility test of aspergillosis strains to voriconazole will be performed in the Centre for Medical Mycology and Mycoses, First Hospital, Peking University, and the performance will be according to the Clinical and Laboratory Standards Institute (CLSI) standard M38-A2 microdilution methods.
Serum galactomannan (GM) test will be performed twice per week for the first two weeks. A double-sandwich ELISA GM assay was used. A cut-off of optical density index (ODI) >0.5 was taken as positive.
Voriconazole serum levels will be measured on day 4, day 7, day 10, and day 14 (all trough levels). In brief, quantitative analysis of voriconazole was performed using high-performance liquid chromatography coupled with tandem mass spectrometry.
Genotyping of CYP2C19 will be performed using 3 ml of peripheral blood sampled into EDTA (ethylenediaminetetraacetic acid) tubes at day 4. Genomic DNA was extracted from blood leukocytes with the use of a DNA extraction kit. Genotyping was confirmed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. Individuals can be divided into three groups according to the CYP2C19 genotype. Those who inherit two mutant CYP2C19 alleles (*2 and/or *3) have a reduced capacity to metabolize CYP2C19 substrates and are defined as poor metabolizers (PMs). Individuals who are homozygous (*1/*1) for wild-type CYP2C19*1 or 1 wild-type allele and 1 CY¬P2C19*17 have efficient enzymes to metabolize CYP2C19 substrates and are defined as extensive metabolizers (EMs). Subjects who are heterozygous (*1/*2, *1/*3) for wild-type CYP2C19*1 are defined as intermediate metabolizers (IMs)
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| invasive pulmonary aspergillosis | – | Drug: VoriconazolePatients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision in five hospital, Jinan, China |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision
Key inclusion criteria (6 listed)
- Proven, probable, or possible invasive pulmonary aspergillosis (IPA)
- Acute IPA defined as duration of clinical syndrome of <30 days.
- Treatment with voriconazole
- At least 18 years and older
- Weight >40 kg and ≤120 kg
Key exclusion criteria (5 listed)
- Patients allergic to azole(s)
- Patients who heve been prescribed voriconazole before
- Positive urine pregnancy test (if female)
- Patients with aspergilloma or chronic aspergillosis ( >1 month duration )
- Anticipated survival of less than 5 days or Karnofsky score <=20
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 |
|---|---|---|
| VoriconazoleAlso: Voriconazole Intravenous Solution 200 mg, Voriconazole Tablet 50 mg / Voriconazole Tablet 200 mgPatients with creatinine clearance at least 50 ml/min will be treated with voriconazole by intravenous drip infusion at the dose of 6 mg/kg twice daily on the first day (Day 1) and 4 mg/kg twice daily from day 2 onward. The IV treatment is at least 7 days. Then switch to 200 mg orally twice daily between meals. The total treatment duration is at least 14 days Patients with creatinine clearance <50 ml/min will be treated with oral voriconazole (loading dose of 400 mg twice daily followed by maintenance dose of 200 mg twice daily between meals for at least 14.0 days). | Drug | invasive pulmonary aspergillosis |
Primary outcome
voriconazole trough level
Time frame: one year
1 secondary outcome
Overall mortality
Time frame: one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2014.
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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.
Shifang Ding, Ph.D. study chair
Qilu Hospital of Shandong University
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 Pulmonary Aspergillosis, run by dingshifang 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 6 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 1 Apr 2014. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shifang Ding, Ph.D. (18560081003 ext. +86, dingshifang@sdu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
voriconazole trough level (time frame: one year). 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 1 Apr 2014.