If the data
Medication will be compared using the Chi-square test. If the data safety monitoring board (DSMB) (see below) has concern regarding the incidence of serious adverse events, it can request unblinded data. The investigators will remain blinded for the groups until the study is completed. If complications occur significantly more often in the intervention group (P 0.05), the study is terminated due to harm.Statistical analysiswill be performed with SPSS version 18.1 (SPSS Inc., Chicago, IL, USA).Study organizationPatient characteristics will be compared and described by appropriate statistics. 3-(2-Bromo-5-hydroxyphenyl)acrylic acid Data will be analyzed on an intention-to-treat basis. Normally distributed variables will be expressed by their mean and standard deviation and non-normally distributed variables will be expressed by their medians and 95 confidence levels. Categorical variables will be expressed as N ( ). To test for normality, a D'Agostino and Pearson omnibus test will be performed [33]. Differences between groups will be tested by Student's t-test for normally distributed data and Mann hitney U-test for not normally distributed data. Categorical variables will be compared with the Chisquare test or Fisher's exact tests or when appropriate as relative risks. The difference of the primary effect variables will be analyzed using the Mann hitney U-test. The rate of freedom from ventilation will be analyzed according to the Kaplan-Meier method [34] and the results will be compared with the log-rank test hazard ratio's are reported with 95 confidence limits. To take into account the stratification factors, we will perform an adjusted analysis. TBSA levels are group level data that will be included as a second level covariate in a multilevel linear regression model to assess the adjusted effect of our randomized treatment. Also the treatment effect on coagulation markers is investigated. Because they are clustered within each patient (repeated measurements) we will also use a multilevel model to evaluate the influence of the cluster effect on the model fit, that PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/4155310 is we will PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/8627573 compare the model fit without a second level (the patient) with the model fit that includes the patient as a second level. When appropriate, statistical uncertainty will be expressed by the 95 confidence levels. Statistical significance is considered to be at a P of 0.05. AnalysisThe Steering Committee is composed of the principal investigators of the participating centers who contribute to the design and revisions of the study protocol. The national coordinators in the Netherlands and in Belgium ensure that all local necessary ethical and regulatory approvals are obtained before start of patient inclusion. In individual participating 1-(4-Bromo-2-pyridyl)piperazine centers, local coordinators provide scientific and structural leadership in their center. They guarantee the integrity of data collection and ensure timely completion of case report forms (CRFs). The trial coordinator trains and monitors the participating centers to ensure the study is conducted according to ICH-GCP guidelines [35], guarantees the integrity of data collection and ensures timely completion of CRFs. An independent monitor performs study monitoring. The independent DSMB is composed of four independent persons (Prof. Dr. Marcelo Gama de Abreu, Prof. Dr. Samir Jaber, Prof. Dr. Paolo Pelosi, and Prof. Dr. Antonio Artigas Ravent ). The DSMB reviews the overall status of the program (number of patients enrolled overall and in each center, adherence to the pro.