Study setting {9}
The study will be conducted in the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, a large Grade-A Tertiary Hospital in Guangzhou.
Eligibility criteria
Inclusion criteria
The following are the inclusion criteria:
- Patients 18–85 years of age;
- Patients with the signing of informed consent and confirming enrollment;
- ACLF was diagnosed according to guidelines for diagnosis and treatment of liver failure(2018)[13]: a presentation of extreme fatigue and severe gastrointestinal symptoms (anorexia, abdominal distension, nausea, and vomiting), progressive jaundice over a short period (total serum bilirubin≥10×ULN or a daily rise≥17μmol/L), a pronounced bleeding tendency (PTA≤40% or INR≥1.5) and any degree of potential complications(encephalopathy, clinical ascites, etc.) based on ongoing chronic liver diseases.
- IPA was diagnosed according to the latest EORTC/MGC consensus definition updated in 2020[14], including proven and probable IPA:
- Proven IPA: Histopathologic examination of a pulmonary specimen obtained by needle aspiration or biopsy in which hyphae or melanized yeast-like forms are seen accompanied by evidence of associated tissue damage, or recovery of the aspergillus by the culture of the alveolar lavage fluid obtained by a sterile fiberoptic bronchoscope lavage from a normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process.
- Probable IPA: Host factors+Clinical features(fever, cough, sputum, and other symptoms; signs such as rales in the lungs; pulmonary imaging in support of aspergillus infection)+Mycological evidence.
Exclusion criteria
The following are the exclusion criteria:
- Pregnant or lactating women;
- Patients with acute fatty liver in pregnancy;
- Patients with HIV co-infection;
- Patients accompany with severe underlying diseases;
- History of allergic to voriconazole.
Dropout criteria
The following are the dropout criteria:
- Patients with ALT or TBiL continuous elevation(more than 5 or 2 times higher than the baseline);
- Patients with central nervous system toxicity such as hallucinations and psychiatric abnormalities, and voriconazole concentrations persistently exceeding 6 mg/L, which cannot be relieved by reducing the dose to 50mg qd;
- Patients who withdraw their consent during the study.
Who will take informed consent? {26a}
Informed consent will be obtained by the investigators.
There will be an investigator on our team who will be specifically responsible for engaging with patients to participate in the study.
There will be an investigator on our team who will be specifically responsible for engaging with patients to participate in the study. The investigator will be responsible for providing each patient and family member with a Participant Information and Consent Form (PICF) describing the purpose and procedures of the study, foreseeable benefits and potential risks of participation, information on data protection procedures, and the option to withdraw from the study at any time, and no reason is required, which should be read by the patient. The investigator will answer any questions the patient and family members may have, and both the patient or his or her family and the investigator will sign the informed consent form to demonstrate the patient's and family's full understanding of the study. Written informed consent must be obtained from all participants prior to any trial-related procedures and prior confirmation that inclusion/exclusion criteria are met during the eligibility assessment is required before patient enrollment.
Additional consent provisions for collection and use of participant data and biological specimens {26b}
In the PICF, the participants will be informed about the use and storage of personal data and biological specimens collected during their participation in the trial. The PICF also contains information concerning the personnel who can access the data collected during this trial and the period that the data will be kept following the study’s completion. By signing the informed consent form, the participants agree to the terms addressed in the PICF.
Interventions
Explanation for the choice of comparators {6b}
Instruction of voriconazole shows no recommendation for patients with severe liver cirrhosis (Child-Pugh C) and liver failure, so the choice of comparators in this study is based on the recent research on related topics and the previous retrospective studies of our research group. The recommended protocol of voriconazole for Child-Pugh A or B liver cirrhosis was chosen as a control to best determine any effects of the interventions.
Intervention description {11a}
Eligible patients will be randomized to either the experimental group or the control group. According to the recent research on related topics and the previous retrospective studies of our research group, the experimental group will receive the optimized voriconazole regimen: first loading dose, 6mg/Kg, ivgtt, q12; second loading dose, 2mg/Kg, ivgtt, q12; maintenance dose, 2mg/Kg, ivgtt, q12. All enrolled patients will receive routine symptomatic treatment.
Criteria for discontinuing or modifying allocated interventions {11b}
Persistent high trough concentrations are an independent risk factor for hepatic and central toxicity of voriconazole. Therefore, if ALT or TBiL is persistently elevated(more than 5 or 2 times higher than the baseline) or central nervous system toxicity such as hallucinations and psychiatric abnormalities occur, and voriconazole concentrations persistently exceeding 6 mg/L, which cannot be relieved by reducing the dose to 50mg qd, voriconazole can be discontinued and replaced with echinocandins for antifungal treatment or even withdrawn from the trial. A patient may also be withdrawn from the study for the following reasons: (1) lost to follow-up; or (2) withdrawal of consent.
Strategies to improve adherence to interventions {11c}
The following measures will be, and or have been, taken to improve adherence to interventions and follow-up:
- All participants will be informed of the study procedures, as well as potential benefits and risks to make them fully understand the significance of their involvement in the study.
- All participants will receive two free voriconazole blood tests and will be able to use first-line therapeutic agents with closely monitored drug blood levels and adverse effects for better outcomes.
Relevant concomitant care permitted or prohibited during the trial {11d}
There will be no restrictions regarding concomitant care during the trial.
Provisions for post-trial care {30}
All patients will return to standard care after the trial.
Outcomes {12}
Primary outcome
The primary endpoint will be the antifungal efficacy of voriconazole. The responses to antifungal therapy in patients with IPA will refer to the EORTC consensus definitions on defining responses to therapy, including complete response and partial response[15].
Secondary outcomes
The secondary endpoints will include the following: the plasma voriconazole concentration; the laboratory examination(CRP, PCT, ESR, etc.); chest CT; adverse events; and the mortality at week 4 and 8.
Participant timeline {13}
The participant timeline is presented in Figs. 2.
Sample size {14}
We referred to a study about drug monitoring and safety of voriconazole therapy in patients with Child-Pugh class B and C cirrhosis, this study suggested that about 30% of patients in group B(loading dose, 0.2, ivgtt, q12×2; maintenance dose: 0.1, ivgtt, q12) had voriconazole Cmin> 5 mg/L on the third day of treatment[16].
Based on pharmacokinetic knowledge, we estimate that the rate of patients in the experimental group in this study with Cmin >5 mg/L after 3 days of treatment with voriconazole will not be lower than that in group B described above. The resulting sample size was calculated as follows:
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)
Substituting into the formula: NC≈42.16. By grouping 1:1, then at least 43 cases were taken from each group. Considering 10% dropout, the study will require recruiting approximately 96 participants for all the groups (n = 48 in each group) to adequately test the assumption.
Recruitment {15}
The subjects will be recruited from the inpatients in the Infectious Department of the Third Affiliated Hospital of Sun Yat-Sen University. Recruitment is expected to begin in August 2021 and end in December 2023.
Assignment of interventions: allocation
Sequence generation {16a}
After inclusion in the trial, the randomization adopts a simple randomization method, and random numbers are generated through computer software (SAS9.4) by the statistician.
Concealment mechanism {16b}
The method of allocation concealment is envelope concealment. Random numbers will be put into uniform envelopes. Then, subjects will be given uniform envelopes according to the order of inclusion and will be assigned random numbers in the envelopes.
Implementation {16c}
After the participant's eligibility has been confirmed and informed consent has been received, the participant will be randomized into the trial. A form will be provided to investigators and will be used to collate the necessary information prior to randomization. Only when all eligibility criteria and baseline data items have been provided, a trial number will be allocated. Participants will be randomized at the level of the individual in a 1:1 ratio to either the experimental group or the control group. The interventions will be implemented based on randomization by investigators.
Assignment of interventions: Blinding
Who will be blinded {17a}
This study is a non-double-blind trial.
Procedure for unblinding if needed {17b}
There should not be any need to unblind the participants.
Data collection and management
Plans for assessment and collection of outcomes {18a}
A predeveloped questionnaire will be completed with patients’ socio-demographic characteristics and required baseline clinical information.
The rest of the information required for the experiment will be collected and assessed as follows:
- Evaluation of plasma voriconazole concentration measurement: the measurement will be carried out half an hour before the second, third, fifth, seventh, and fifteenth doses, once a week after the fifteenth dose, and every two weeks after week 4.
- Evaluation of laboratory examination(including the following: blood routine test, CRP, PCT, ESR, FER, LDH, G test, GM test, hepatic and renal function, coagulation function, arterial blood gas analysis, and blood ammonia): week 1, 2, 3, 4, 6, 8 after the start of the study.
- Evaluation of imaging tests(including chest CT): once every 2 weeks
- Evaluation of Child-Pugh classification and MELD score: week 1, 2, 3, 4, 6, 8 after the start of the study.
Schedule of assessments is detailed in table 1.
Plans to promote participant retention and complete follow-up {18b}
The purpose and importance of the trial will be explained through the research team and PICF during participant recruitment. Participants have the right to withdraw from the trial at any time and for any reason without compromising their medical care and routine treatment by the treatment team or institution. If a participant withdraws from the trial before the end of the study and because the data will be recorded anonymously, an intention-to-treat analysis will be performed on the data for such patients. If a patient withdraws consent during the conduct of the trial and does not wish to consent to the use of data already collected, and if these particular data are retrievable, the investigator will delete the data accordingly.
viewpoint
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V1
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V2
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V3
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V4
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V5
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V6
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V7
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V8
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V9
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V10
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V11
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time point
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0(baseline)
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12h
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24h
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48h
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72h
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week 1
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Week 2
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Week 3
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Week 4
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Week 6
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Week 8
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Use of
Voriconazole
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Before treatment
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Before the 2nd dose
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Before the 3rd dose
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Before the 5th dose
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Before the 7th dose
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week 1
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Week 2
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Week 3
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Week 4
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Week 6
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Week 8
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Time-window
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-7
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0
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0
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0
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0
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±1
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±2
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±2
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±2
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±3
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±3
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informed
consent
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√
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essential information
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√
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Inclusion/exclusion criteria
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√
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Previous treatments
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√
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Previous medicine
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√
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CYP2C19 gene
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√
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Blood routine
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inflammation indicators
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coagulation function
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Condition evaluation
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SAE
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Data management {19}
Data will be collected through a paper-based questionnaire, and the collected information will remain anonymous. All data recorded on paper forms will be safely stored in the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, following data protection procedures.
Confidentiality {27}
Participants will be assigned a subject's number for de-identification purposes and all the collected data tables will be identified by the subject's number only. All data in this study will be stored in a special filing cabinet in the Third Affiliated Hospital of Sun Yat-Sen University. At the same time, we will set access to the file to ensure the security and confidentiality of the data.
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
No biological specimens will be collected for future genetic or molecular analysis.
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
In this study, a separate statistical analysis plan will be developed to analyze the data of the treatment group and the control group. The analyses will be based on Consolidated Standards of Reporting Trials guidelines, and all analyses will be on the principle of intention-to-treat, that is, all participants will be analyzed even if some subjects will fail to follow the original plan during the study. This analysis method can better evaluate the effect of the intervention, reduce bias and be closer to the actual clinical situation. Our researchers are responsible for the follow-up to ensure that relatively complete data are obtained. Subjects who lacked data on the main results will be excluded in the study from the beginning.
PASW18.0 statistical software will be used to analyze the data. The counting data will be expressed by rate, and the rate will be compared by the chi-square test. Continuous normal distribution data will be expressed as mean±standard deviation, t-test will be used for comparison between the two groups, non-normal data will be expressed as median (quartile spacing), Mann-WhitneyTest method will be used for comparison between the two groups, and χ 2 test will be used for counting data. P < 0.05 indicates that the difference is statistically significant. GraphPadPrism5 software will be to draw.
Interim analyses {21b}
No interim analyses are planned.
Methods for additional analyses (e.g. subgroup analyses) {20b}
No interim analyses are planned.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
No imputation of missing data will be performed for statistical analysis.
Plans to give access to the full protocol, participant level-data and statistical code {31c}
The complete trial protocol will be shared upon reasonable request. Group-level anonymized data may be shared with external investigators at the end of the trial after obtaining institutional approval to release the data externally. The results of the trial will be published in peer-reviewed journals and presented at conferences. Study results will be released to participating patients.
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
The trial will be conducted by the study research team, including the Infectious Diseases Department staff and masters. The principal investigator takes responsibility for the supervision of the trial and ensures compliance with the study protocol. The statistical research plan and statistical analysis will be supervised by the Research and Ethics Unit, The Third Affiliated Hospital of Sun Yat-Sen University.
Composition of the data monitoring committee, its role and reporting structure {21a}
The data monitoring committee is unnecessary in this trial because this study will not involve participants with severe diseases and communication disabilities or interventions that can risk participants' lives. Instead, the oversight of data quality will be provided by the Research and Ethics Unit, The Third Affiliated Hospital of Sun Yat-Sen University.
Adverse event reporting and harms {22}
All participants will be monitored concerning any possible adverse events related to the administration of interventions, such as exacerbation of IPA, deterioration of liver function, the emergence of other infections, et al. As such, all adverse events (AEs) observed or reported by the patient are collected and evaluated for relatedness to trial intervention, seriousness, severity, expectedness, and outcome. AEs are defined in the Good Clinical Practice (GCP) guideline.
Frequency and plans for auditing trial conduct {23}
The study team will audit the data regularly. The audit may be performed by The Third Affiliated Hospital of Sun Yat-Sen University Research and Ethics Unit, its staff to evaluate the clinical study conduct and compliance with the protocol, standard operating procedures, GCP, and the applicable regulatory requirements.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}
The Principal Investigator will be responsible for any protocol amendments and their follow-up process. Protocol amendments will be submitted to the Ethics Committee and implemented upon approval. The principal investigator is responsible for disseminating changes to the protocol and all study team members will receive adequate training on protocol amendments.
Dissemination plans {31a}
The final data will be publicly disseminated. The results will be presented at relevant meetings and published in appropriate journals after the trial and analysis.