<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01669577</url>
  </required_header>
  <id_info>
    <org_study_id>1081/09</org_study_id>
    <nct_id>NCT01669577</nct_id>
  </id_info>
  <brief_title>Independent Predictors of Mortality in Polytrauma Patients</brief_title>
  <official_title>Independent Predictors of Mortality in Polytrauma Patients: a Prospective, Observational, Longitudinal Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundação de Amparo à Pesquisa do Estado de São Paulo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prospective observational trial searching for independent predictors of mortality. Data was&#xD;
      collected at trauma scene, ER, three and 24 hours of hospital stay.The patients will be&#xD;
      followed for 30 days after hospital admission.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study protocol was approved by the Institutional Medical Ethics Committee (CAPPesq&#xD;
      1081/09) and received financial support from the São Paulo State Research Foundation&#xD;
      (Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP) under no. 2010/03315-4.&#xD;
&#xD;
      At the end of data prospecting, 334 patients with severe trauma (Injury Severity Score, ISS,&#xD;
      &gt;15), assisted by the rescue system and taken to HCFMUSP-Hospital das Clínicas da Faculdade&#xD;
      de Medicina da Universidade de São Paulo- (by land and helicopter) were included in the&#xD;
      study. This screening strategy included trauma patients with severe confirmed bleeding,&#xD;
      patients with severe traumatic brain injury (TBI) and patients facing high-energy trauma (a&#xD;
      marked characteristic of this trauma center). Patients under 18 years of age were excluded (&#xD;
      Figure 1).&#xD;
&#xD;
      In total, 78 patients were excluded because they did not fit the above criteria, leaving 256&#xD;
      patients for analysis. Of this total, 34 patients died before arriving at the emergency room,&#xD;
      and 22 were removed from the analysis due to incomplete data, not signing the informed&#xD;
      consent form or due to any situation in which the data collection could compromise victim&#xD;
      care(care Figure(Figure 1).&#xD;
&#xD;
      All patients had data recorded at the following times: 1, at the trauma scene; 2, in the&#xD;
      emergency room; 3, at 3 hours after hospital admission; and 4, at 24 hours after&#xD;
      hospitalization.&#xD;
&#xD;
      Data regarding gender, age, trauma and trauma mechanism, medical procedures performed at all&#xD;
      stages, time until arrival at the hospital and comorbidities were recorded. The clinical data&#xD;
      collected were as follows: systolic blood pressure (SBP); diastolic blood pressure (DBP);&#xD;
      heart rate (HR); respiratory rate (RR); arterial hemoglobin oxygen saturation (SAT); Glasgow&#xD;
      Coma Scale (GCS) score; and pupil pattern. The following laboratory data were collected&#xD;
      through peripheral venipuncture at the hospital stages: pH(hydrogenic potential); base excess&#xD;
      (BE); bicarbonate (BIC); partial oxygen pressure (pO2); partial carbon dioxide pressure&#xD;
      (pCO2); arterial hemoglobin oxygen saturation; lactate; sodium (Na+); potassium (K+); ionized&#xD;
      calcium (Ca2+); glucose; hemoglobin (Hb); hematocrit (Ht); serum creatine phosphokinase&#xD;
      (CPK); platelets and leukocytes. Data regarding volume expansion [crystalloids (CRYSTAL),&#xD;
      colloids (COLO)], diuresis and water balance were also collected. The use of blood products&#xD;
      [packed red blood cells (PRBC), fresh frozen plasma (FFP), platelet concentrates (PLAT),&#xD;
      cryoprecipitate concentrates (concentrates (CRYO)] was computed, and the use of vasoactive&#xD;
      drugs (VAD) was scored at the respective times. Patient follow-up was conducted at the&#xD;
      intensive care unit (ICU), and time of ICU stay (days in the ICU), days under mechanic&#xD;
      ventilation (days under MV), the presence or absence of sepsis, coagulopathy and acute renal&#xD;
      failure (ARF) were recorded.&#xD;
&#xD;
      Blood coagulation data were collected as follows: time point 1, International Normalized&#xD;
      Ratio (INR) and prothrombin time (PT); and time points 2, 3 and 4, INR, PT, activated partial&#xD;
      thromboplastin time (aPTT), the respective ratio between aPTT of patients and controls (R)&#xD;
      and thrombin time (TT).&#xD;
&#xD;
      The following severity indexes were calculated: ISS, revised trauma score (RTS); trauma and&#xD;
      injury severity score (TRISS); and simplified acute physiology score (SAPS) 3 (the latter&#xD;
      when the patient was in the ICU).&#xD;
&#xD;
      At time point 1, blood tests were performed using the i-STAT® device (Abbott, USA; PT/INR and&#xD;
      CG4+ and CG8+ kits). At the hospital stages, the analyses used the clinical analysis&#xD;
      methodology of the HCFMUSP.&#xD;
&#xD;
      Clinical follow-up was conducted for 30 days after initial trauma.&#xD;
&#xD;
      Statistical analyses The sample power analysis was conducted with a significance level of&#xD;
      0.05, power of 0.80, moderate correlation of 0.5 between time periods and assumption that the&#xD;
      variability is equal within each factor (non-sphericity). Due to the effect size between 0.1&#xD;
      and 0.5, there was no need for samples larger than 140 patients. A total of 200 patients&#xD;
      waswere defined conservatively, with a margin for possible deaths. The software G*Power 3.1.7&#xD;
      was used for sample size calculation.&#xD;
&#xD;
      The data analysis was divided into three interconnected parts. The first part refers to the&#xD;
      descriptive data analysis and tests of association with death. The second part addressed the&#xD;
      profiles of the time-dependent measures and their relationship with death through analysis of&#xD;
      nonparametric variance for repeated measures. The third part includes the set of all previous&#xD;
      analyses that resulted in a Generalized Estimating Equation (GEE).&#xD;
&#xD;
      For the first part, the analyses were performed with the overall sample (n=200) subdivided&#xD;
      into two groups: deaths (n=52) and non-deaths (n=148). For qualitative variables, the&#xD;
      two-tailed Fisher's exact test was used, and for quantitative variables, the two-tailed t&#xD;
      test or the two-tailed Mann-Whitney test was used according to the normality of the variable,&#xD;
      which was verified by the Anderson-Darling test.&#xD;
&#xD;
      In the second part, the profiles of each measure over time were analyzed for groups of&#xD;
      survivors and non-survivors. Nonparametric analyses of variance (NPar ANOVA) were conducted.&#xD;
&#xD;
      Finally, in the third part, a GEE model was developed considering the family of binomial&#xD;
      distributions (dichotomous response variable) with logit link function. Only the main effects&#xD;
      of each measure were considered. The NPar ANOVA (p&gt;0.1) was the test used for inclusion in&#xD;
      the model. The variables for the final models were selected using the backward method, with&#xD;
      output alpha equal to 0.05. All part 3 results were interpreted by estimating odds ratios&#xD;
      (OR), their corresponding 95% confidence intervals and significance tests (p-value).&#xD;
&#xD;
      The significance level was set at 0.05, and the free software R 3.0.2 was used for performing&#xD;
      the statistical analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2010</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">June 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Death</measure>
    <time_frame>Within the first 30 days</time_frame>
    <description>30 days after trauma mortality evaluation</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">200</enrollment>
  <condition>Multiple Trauma</condition>
  <arm_group>
    <arm_group_label>severe trauma patients</arm_group_label>
    <description>analysis of blood samples and clinical features</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>analysis of blood samples and clinical features</intervention_name>
    <description>clinical follow up and biochemical analysis blood at 4 time points:1-prehospital; 2-emergency room; 3- surgical center; 4-intensive care unit . 30 days follow up</description>
    <arm_group_label>severe trauma patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Severe trauma patients evaluated at trauma scene&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  severe trauma (ISS - Injury Severity Score- &gt;15)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  under 18 years old patient,&#xD;
&#xD;
          -  technical problems during rescue maneuvers,&#xD;
&#xD;
          -  impossibility of blood sample draw during rescue&#xD;
&#xD;
          -  informed consent not provided&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luiz G Costa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital das Clínicas da Universidade de São Paulo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto Central do Hospital das Clínicas da Universidade de São Paulo</name>
      <address>
        <city>São Paulo</city>
        <zip>05403000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>December 24, 2014</results_first_submitted>
  <results_first_submitted_qc>January 8, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 9, 2015</results_first_posted>
  <last_update_submitted>January 8, 2015</last_update_submitted>
  <last_update_submitted_qc>January 8, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 9, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Luiz Guilherme Villares da Costa</investigator_full_name>
    <investigator_title>Anesthesia division clinical staff physician</investigator_title>
  </responsible_party>
  <keyword>predictors</keyword>
  <keyword>trauma</keyword>
  <keyword>mortality</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Trauma</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>334 patients were collected during São Paulo rescue system activities. Entry criteria was defined as hypotensive patients (SBP&lt;90mmHg at the scene, high-energy traumas, severe TBI); patients under 18 years old were excluded.&#xD;
If calculated ISS &lt; 16 or no informed consent, patients were excluded.</recruitment_details>
      <pre_assignment_details>Pre assignment were not performed, as patients were not known.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Severe Trauma Patients</title>
          <description>intervention : analysis of blood samples&#xD;
analysis of blood samples (0,2 ml): analysis of blood samples (0,2 ml)&#xD;
analysis of blood samples: analysis of blood samples regarding electrolytes, blood gases, glucose, PT/INR collection of vital signs, blood chemistry; severity scores and intensive care unit(ICU) LOS(length of stay) were recorded</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="334">calculated ISS&lt;16, no informed consent, not enough data(complete case analysis), were excluded</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="200">complete case analysis (data missing completely at random)</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="134"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>severe polytrauma patients</population>
      <group_list>
        <group group_id="B1">
          <title>Severe Trauma Patients</title>
          <description>Hypotensive Patients (SBP&lt;90mmHg), severe TBI, high energy traumas All patients must have calculated ISS &gt;15 to be included and a written informed consent should be available</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="200"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Continuous</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37" spread="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Brazil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Death</title>
        <description>30 days after trauma mortality evaluation</description>
        <time_frame>Within the first 30 days</time_frame>
        <population>severe polytrauma patients (ISS&gt;15)</population>
        <group_list>
          <group group_id="O1">
            <title>Severe Trauma Patients</title>
            <description>intervention : analysis of blood samples; vital signs and clinical outcomes recorded&#xD;
analysis of blood samples (0,2 ml): analysis of blood samples (0,2 ml)&#xD;
analysis of blood samples: analysis of blood samples regarding electrolytes, blood gases, glucose, PT/INR</description>
          </group>
        </group_list>
        <measure>
          <title>Death</title>
          <description>30 days after trauma mortality evaluation</description>
          <population>severe polytrauma patients (ISS&gt;15)</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>significance level of 0.05, power of 0.80, moderate correlation of 0.5 between time periods and assumption that the variability is equal within each factor (non-sphericity). Due to the effect size between 0.1 and 0.5, there was no need for samples larger than 140 patients. A total of 200 patients was defined conservatively, with a margin for possible deaths. The software G*Power 3.1.7 was used for sample size calculation.&#xD;
Fischer's test, Mann-Whitney, t-test; Non parametric ANOVA and GEE</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <p_value_desc>arterial hemoglobin Oxygen saturation</p_value_desc>
            <method>ANOVA</method>
            <method_desc>Non parametric(NPar) ANOVA</method_desc>
            <param_type>GEE(Generalyzed Estimation Equation)</param_type>
            <param_value>0.989214</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.982855</ci_lower_limit>
            <ci_upper_limit>0.995613</ci_upper_limit>
            <estimate_desc>GEE model (dichotomous response variable)with logit link function. The NPar ANOVA (p&lt;0.1 for death) was the test used for inclusion in the model variables for the final models - backward method, with alpha equal to 0.05.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>diastolic arterial blood pressure</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <method>ANOVA</method>
            <param_type>GEE</param_type>
            <param_value>0.997280</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.995791</ci_lower_limit>
            <ci_upper_limit>0.998772</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>lactate</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.004</p_value>
            <method>ANOVA</method>
            <param_type>GEE</param_type>
            <param_value>1.046961</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.012521</ci_lower_limit>
            <ci_upper_limit>1.082572</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Glasgow coma score</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANOVA</method>
            <param_type>GEE</param_type>
            <param_value>0.973987</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.965308</ci_lower_limit>
            <ci_upper_limit>0.982744</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>amount of Infused crystalloids</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.023</p_value>
            <method>ANOVA</method>
            <param_type>GEE</param_type>
            <param_value>1.000013</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.000000</ci_lower_limit>
            <ci_upper_limit>1.000025</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days follow up</time_frame>
      <desc>Patients were monitored for adverse outcomes related to venipuncture, as this was the unique intervention.</desc>
      <group_list>
        <group group_id="E1">
          <title>Severe Trauma Patients</title>
          <description>intervention : analysis of blood samples&#xD;
analysis of blood samples (0,2 ml): analysis of blood samples (0,2 ml)&#xD;
analysis of blood samples: analysis of blood samples regarding electrolytes, blood gases, glucose, PT/INR</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <description>1 patient was diagnosed by ultrasound and persistent positive blood cultures. Another foci of infection were discarded and patient treated with antibiotics and systemic anticoagulation( iv non fractionated heparin) until resolution of septic state.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <description>2 patients had skin infection at the peripheral venous acess site (performed at the prehospital stage)</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="200"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>single center trial, majority of TBI and male patients</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Luiz Guilherme Villares da Costa, MD</name_or_title>
      <organization>University of São Paulo</organization>
      <phone>5511985584737</phone>
      <email>lgvc76@yahoo.com.br</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01669577
org study id: 1081/09
nct id: NCT01669577
lead sponsor: 
collaborator: 
has dmc: Yes
Prospective observational trial searching for independent predictors of mortality. Data was
      collected at trauma scene, ER, three and 24 hours of hospital stay.The patients will be
      followed for 30 days after hospital admission.
The study protocol was approved by the Institutional Medical Ethics Committee (CAPPesq
      1081/09) and received financial support from the São Paulo State Research Foundation
      (Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP) under no. 2010/03315-4.

      At the end of data prospecting, 334 patients with severe trauma (Injury Severity Score, ISS,
      >15), assisted by the rescue system and taken to HCFMUSP-Hospital das Clínicas da Faculdade
      de Medicina da Universidade de São Paulo- (by land and helicopter) were included in the
      study. This screening strategy included trauma patients with severe confirmed bleeding,
      patients with severe traumatic brain injury (TBI) and patients facing high-energy trauma (a
      marked characteristic of this trauma center). Patients under 18 years of age were excluded (
      Figure 1).

      In total, 78 patients were excluded because they did not fit the above criteria, leaving 256
      patients for analysis. Of this total, 34 patients died before arriving at the emergency room,
      and 22 were removed from the analysis due to incomplete data, not signing the informed
      consent form or due to any situation in which the data collection could compromise victim
      care(care Figure(Figure 1).

      All patients had data recorded at the following times: 1, at the trauma scene; 2, in the
      emergency room; 3, at 3 hours after hospital admission; and 4, at 24 hours after
      hospitalization.

      Data regarding gender, age, trauma and trauma mechanism, medical procedures performed at all
      stages, time until arrival at the hospital and comorbidities were recorded. The clinical data
      collected were as follows: systolic blood pressure (SBP); diastolic blood pressure (DBP);
      heart rate (HR); respiratory rate (RR); arterial hemoglobin oxygen saturation (SAT); Glasgow
      Coma Scale (GCS) score; and pupil pattern. The following laboratory data were collected
      through peripheral venipuncture at the hospital stages: pH(hydrogenic potential); base excess
      (BE); bicarbonate (BIC); partial oxygen pressure (pO2); partial carbon dioxide pressure
      (pCO2); arterial hemoglobin oxygen saturation; lactate; sodium (Na+); potassium (K+); ionized
      calcium (Ca2+); glucose; hemoglobin (Hb); hematocrit (Ht); serum creatine phosphokinase
      (CPK); platelets and leukocytes. Data regarding volume expansion [crystalloids (CRYSTAL),
      colloids (COLO)], diuresis and water balance were also collected. The use of blood products
      [packed red blood cells (PRBC), fresh frozen plasma (FFP), platelet concentrates (PLAT),
      cryoprecipitate concentrates (concentrates (CRYO)] was computed, and the use of vasoactive
      drugs (VAD) was scored at the respective times. Patient follow-up was conducted at the
      intensive care unit (ICU), and time of ICU stay (days in the ICU), days under mechanic
      ventilation (days under MV), the presence or absence of sepsis, coagulopathy and acute renal
      failure (ARF) were recorded.

      Blood coagulation data were collected as follows: time point 1, International Normalized
      Ratio (INR) and prothrombin time (PT); and time points 2, 3 and 4, INR, PT, activated partial
      thromboplastin time (aPTT), the respective ratio between aPTT of patients and controls (R)
      and thrombin time (TT).

      The following severity indexes were calculated: ISS, revised trauma score (RTS); trauma and
      injury severity score (TRISS); and simplified acute physiology score (SAPS) 3 (the latter
      when the patient was in the ICU).

      At time point 1, blood tests were performed using the i-STAT® device (Abbott, USA; PT/INR and
      CG4+ and CG8+ kits). At the hospital stages, the analyses used the clinical analysis
      methodology of the HCFMUSP.

      Clinical follow-up was conducted for 30 days after initial trauma.

      Statistical analyses The sample power analysis was conducted with a significance level of
      0.05, power of 0.80, moderate correlation of 0.5 between time periods and assumption that the
      variability is equal within each factor (non-sphericity). Due to the effect size between 0.1
      and 0.5, there was no need for samples larger than 140 patients. A total of 200 patients
      waswere defined conservatively, with a margin for possible deaths. The software G*Power 3.1.7
      was used for sample size calculation.

      The data analysis was divided into three interconnected parts. The first part refers to the
      descriptive data analysis and tests of association with death. The second part addressed the
      profiles of the time-dependent measures and their relationship with death through analysis of
      nonparametric variance for repeated measures. The third part includes the set of all previous
      analyses that resulted in a Generalized Estimating Equation (GEE).

      For the first part, the analyses were performed with the overall sample (n=200) subdivided
      into two groups: deaths (n=52) and non-deaths (n=148). For qualitative variables, the
      two-tailed Fisher's exact test was used, and for quantitative variables, the two-tailed t
      test or the two-tailed Mann-Whitney test was used according to the normality of the variable,
      which was verified by the Anderson-Darling test.

      In the second part, the profiles of each measure over time were analyzed for groups of
      survivors and non-survivors. Nonparametric analyses of variance (NPar ANOVA) were conducted.

      Finally, in the third part, a GEE model was developed considering the family of binomial
      distributions (dichotomous response variable) with logit link function. Only the main effects
      of each measure were considered. The NPar ANOVA (p>0.1) was the test used for inclusion in
      the model. The variables for the final models were selected using the backward method, with
      output alpha equal to 0.05. All part 3 results were interpreted by estimating odds ratios
      (OR), their corresponding 95% confidence intervals and significance tests (p-value).

      The significance level was set at 0.05, and the free software R 3.0.2 was used for performing
      the statistical analyses.
observational model: Cohort
time perspective: Prospective
measure: Death
time frame: Within the first 30 days
description: 30 days after trauma mortality evaluation
arm group label: severe trauma patients
description: analysis of blood samples and clinical features
intervention type: Procedure
intervention name: analysis of blood samples and clinical features
description: clinical follow up and biochemical analysis blood at 4 time points:1-prehospital; 2-emergency room; 3- surgical center; 4-intensive care unit . 30 days follow up
arm group label: severe trauma patients
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Luiz G Costa, MD
role: Principal Investigator
affiliation: Hospital das Clínicas da Universidade de São Paulo
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Luiz Guilherme Villares da Costa
investigator title: Anesthesia division clinical staff physician
mesh term: Multiple Trauma
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: single center trial, majority of TBI and male patients
point of contact: 