Here is the design of a clinical trial:

Official Title: A Multicenter, Random Control Study: Early Use of Airway Pressure Release Ventilation Updated (APRVplus) Protocol in Acute Respiratory Disease Syndrome (ARDS)

Included conditions:
- Acute Respiratory Distress Syndrome

Study Armgroups:
- {'label': 'Early use of APRVplus protocol in ARDS', 'type': 'EXPERIMENTAL', 'description': 'physiology-driven APRVplus protocol', 'interventionNames': ['Procedure: APRVplus protocol']}
- {'label': 'Low tidal volume ventilation', 'type': 'OTHER', 'description': 'Low tidal volume lung protective ventilation', 'interventionNames': ['Procedure: Low tidal volume ventilation']}

Interventions:
- {'type': 'PROCEDURE', 'name': 'APRVplus protocol', 'description': 'Physiology-driven APRVplus protocol', 'armGroupLabels': ['Early use of APRVplus protocol in ARDS']}
- {'type': 'PROCEDURE', 'name': 'Low tidal volume ventilation', 'description': 'Low tidal volume lung protective ventilation', 'armGroupLabels': ['Low tidal volume ventilation']}

Primary Outcomes:
- {'measure': 'mortality', 'description': 'mortality at Day28', 'timeFrame': 'Day 28'}

Please estimate the sample size based on the assumption: 
90% power, two-sided significance level of 0.05, and approximately 10% loss in follow-up.
Sample size estimation and statistical analysis
        
          Sample size
          Based on previous research indicating a 37% mortality rate at ICU 28 days among moderate-severe ARDS patients receiving low tidal volume ventilation strategy [41], we postulated a 10% reduction in ICU 28-day mortality following the implementation of the early pathophysiology-directed APRV ventilation strategy compared to low tidal volume lung protective ventilation. Considering a hazard ratio of 0.66, a 90% power, and a two-sided significance level of 0.05, it is estimated that 762 patients are required to detect this difference. Accounting for approximately 10% loss in follow-up, enrollment of 840 patients (420 in each group) is necessary. An interim analysis will be conducted once 50% of the sample size is reached.
          
Table 2Overview of the schedule of enrolment, interventions and assessmentsAPRV airway pressure release ventilation, LTV low tital ventilation
        
        
          Statistics
          Continuous variables will be presented as mean and standard deviation, or median and interquartile ranges (IQR). Categorical data will be described with counts and percentages. Continuous variables with a normal distribution will be analyzed using the Studentâs t-test, while those with a non-normal distribution will be compared using the KruskalâWallis analysis of variance. Dichotomous or nominal categorical variables will be analyzed using either the Pearson Chi-square or Fisherâs exact test. The trend over time in oxygenation and respiratory mechanics will be compared between the LTV group and APRV group using repeated-measures analysis. A two-sided P value of <â0.05 is considered statistically significant.
          All analyses will adhere to the intention-to-treat principle (per protocol analysis). The primary outcome will be assessed using Kaplan-Meier curves and the ratio will be calculated with a 95% confidence interval using the Cox proportional hazard model. We plan to conduct a sensitivity analysis for the primary outcome using multiple imputation techniques only if follow-up data of 1% or more of the patients is lost. Interim analyses will be performed after recruiting half of the planned sample size to evaluate effects on clinical outcomes. The data monitoring committee would consider stopping the trial if there was evidence of harm with a one-sided P valueâ<â0.01.
          We will estimate the effects of the intervention using generalized linear models employing gamma distributions for lengths of ICU and hospital stay) or a truncated Poisson distribution (ventilator-free days). The treatment effect on 28-day mortality will be in subgroups based on PaO2:FIO2 (â¤â100 vs.â>â100 mmHg) and pulmonary vs. extrapulmonary ARDS.
          All analyses will be performed using the R software and subgroups will be evaluated using the chi-square test for homogeneity, we will employ the statistical software R Project Version 4.1.3 for Windows to carry out the analyses.
        
        
          Data monitoring committee
          A Data Monitoring Committee comprising independent epidemiologists and intensivists will be established to oversee the study. The committee will be responsible for assessing the potential risks and benefits associated with the research, and will provide recommendations on whether to continue with the planned study or cease recruitment. This decision will be based on evidence indicating a higher mortality rate in the experimental group compared to the control group. Any safety-related adverse events will be promptly reported to the siteâs Institutional Review Board (IRB). Site investigators will be informed of the event and will subsequently submit a comprehensive written report to the local IRB. Sites will notify the research team of any related adverse events within a week of their discovery and complete the appropriate eCRF. The research team will provide the Data Monitoring Committee with summaries of all reports at least biannually. The Committee will convene via teleconference or in-person meetings at 25%, 50%, and 75% of enrollment, or earlier if necessary, to review adverse events.
        
        
          Ethics and dissemination
          The protocol has received approval from the Ethics Committee of West China Hospital of Sichuan University (approval number 2019âââ337). Additionally, approvals for the protocol and informed consent documents are obtained from the Institutional Review Board of each participating institution before enrolling study participants. Written informed consent is required and obtained from legally authorized representatives at the respective study site. Trial methods and results will be reported according to the Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines [42]. The primary outcome of the study will be published as the first article and additional results extrapolated from the data could be published in separate articles. The findings of this study will be disseminated in peer-reviewed journals, presented at scientific conferences, and shared with the practice.
        
        
          Protocol amendments
          Any modifications to the study will prompt simultaneous protocol adjustments, which will be promptly submitted for approval to the institutional review board. The changes will only be executed following the endorsement of the ethical committee. Upon approval, the amendments will be disseminated to other participating sites, and ClinicalTrials.gov will be promptly updated regarding any significant changes. If required, the study team will provide protocol training for the amendments.