<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/NCT03785899</url>
  </required_header>
  <id_info>
    <org_study_id>optimalSPOC</org_study_id>
    <nct_id>NCT03785899</nct_id>
  </id_info>
  <brief_title>Automatic Oxygen Control (SPOC) in Preterm Infants</brief_title>
  <acronym>optimalSPOC</acronym>
  <official_title>Automatic Oxygen Control (SPOC) in Preterm Infants - Evaluation of a Revised Algorithm and Effect of Averaging Time of Pulse Oximetry Signal</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Tuebingen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fritz Stephan GmbH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital Tuebingen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Single-center, randomised controlled, cross-over clinical trial in preterm infants born at&#xD;
      gestational age below 34+1/7 weeks receiving supplemental oxygen and respiratory support&#xD;
      (continous positive airway pressure (CPAP) or non-invasive ventilation (NIV) or invasive&#xD;
      ventilation (IV)). Routine manual control (RMC) of the fraction of inspired oxygen (FiO2)&#xD;
      will be tested against RMC supported by automatic control (SPOC) with &quot;old&quot;-algorithm and RMC&#xD;
      supported by CLAC with &quot;new&quot;-algorithm.&#xD;
&#xD;
      The first primary hypothesis is, that the use of the &quot;new&quot; algorithm results in more time&#xD;
      within arterial oxygen saturation (SpO2) target range compared to RMC only. The a-priori&#xD;
      subordinate hypothesis is, that the new algorithm results in more time within SpO2 target&#xD;
      range compared to SPOCold.&#xD;
&#xD;
      The second primary hypothesis is, that the use of 2 seconds averaging time of the SpO2 Signal&#xD;
      results in more time within arterial oxygen saturation (SpO2) target range compared to the&#xD;
      use of 8 seconds averaging interval of the SpO2 signal.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND AND OBJECTIVE In preterm infants receiving supplemental oxygen, routine manual&#xD;
      control (RMC) of the fraction of inspired oxygen (FiO2) is often difficult and time&#xD;
      consuming. The investigators developed a system for closed-loop automatic control (SPOC) of&#xD;
      the FiO2. The objective of this study is to test a revised, &quot;new&quot; algorithm with 3 adaptions&#xD;
      against the former &quot;old&quot; algorithm and against RMC. The 3 adaptions are:&#xD;
&#xD;
        1. Faster re-adjustment to baseline-FiO2 (baseline FiO2: mean FiO2 during the previous&#xD;
           5min)&#xD;
&#xD;
        2. Delayed reduction of FiO2 below baseline FiO2&#xD;
&#xD;
        3. Maximum FiO2 adjustable by user&#xD;
&#xD;
      The first primary hypothesis is, that the application of SPOCnew in addition to RMC results&#xD;
      in more time within arterial oxygen saturation (SpO2) target range compared to RMC only. The&#xD;
      a-priori subordinate hypothesis is, that the revised algorithm is more effective as the old&#xD;
      algorithm to maintain the SpO2 in the target range.&#xD;
&#xD;
      The second primary hypothesis is, that the shortening of averaging time used for the SpO2&#xD;
      Signal from 8 seconds to 2 seconds results in more time within SpO2 target range for both,&#xD;
      SPOCnew and SPOCold.&#xD;
&#xD;
      Further hypotheses for exploratory testing are, that the SPOC new algorithm will achieve a&#xD;
      lower proportion of time with SpO2 above and below the target range, hyper- and hypoxia and&#xD;
      an improved stability of cerebral oxygenation (measured as rcStO2 and rcFtO2E determined by&#xD;
      Near-infrared spectroscopy) compared with SPOCold and RMC. Reduction of staff workload&#xD;
      (estimated by number of manual adjustments per hour) by SPOC. Validation of a clinical&#xD;
      scoring tool to monitor severity of apnea of prematurity.&#xD;
&#xD;
      STUDY DESIGN The Study is designed as a single-center, randomized controlled, cross-over&#xD;
      clinical trial in preterm infants receiving mechanical ventilation or nasal continuous&#xD;
      positive airway pressure or non-invasive ventilation and supplemental oxygen (FiO2 above&#xD;
      0.21). Within a 30-hour period the investigators will compare 6 hours of RMC with 12-hour&#xD;
      periods of RMC supported by SPOCnew algorithm or SPOCold algorithm, respectively. During&#xD;
      intervals with SPOC control the SpO2 Signal averaging time will be 2 second or 8seconds ,&#xD;
      respectively, for 6 hours each.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 3, 2018</start_date>
  <completion_date type="Anticipated">August 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of time with SpO2 within target range</measure>
    <time_frame>30 hours</time_frame>
    <description>Comparison of proportion of time with SpO2 within target range and time above target range if no supplemental oxygen was administered at that time and within the preceding 30sec between the five treatment modalities</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Time with SpO2 above target range</measure>
    <time_frame>30 hours</time_frame>
    <description>Comparison of proportion of time with SpO2 above target range if supplemental oxygen was administered at that time or within the preceding 30sec .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Time with SpO2 below target range</measure>
    <time_frame>30 hours</time_frame>
    <description>Comparison of proportion of time with SpO2 below target range.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Time with Hypoxia</measure>
    <time_frame>30 hours</time_frame>
    <description>Comparison of proportion of time with SpO2 below 80%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Time with Hyperoxia</measure>
    <time_frame>30 hours</time_frame>
    <description>Comparison of proportion of time with SpO2 above 97% if supplemental oxygen was administered at that time or at anytime during the previous 30 seconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stability of cerebral oxygenation</measure>
    <time_frame>30 hours</time_frame>
    <description>&quot;Area under the curve&quot; of cerebral tissue saturation or fraction of tissue oxygen extraction outside of the infants Median +- 5% or outside of the &quot;safe&quot; interval of 55-80% rcStO2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe hypoxemic episodes</measure>
    <time_frame>30 hours</time_frame>
    <description>Rate of episodes with SpO2 &lt;80% for at least 60seconds</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Staff workload</measure>
    <time_frame>30 hours</time_frame>
    <description>number of manual adjustments of inspired oxygen per time</description>
  </other_outcome>
  <other_outcome>
    <measure>Validation of clinical Apnea Score</measure>
    <time_frame>30 hours</time_frame>
    <description>Validation of a modified Apnea Score monitored by clinical staff by correlation between Score and other secondary outcomes. The modified Apnoea Score aims to quantify the burden from apnoea-bradycardia-syndrome by assigning 1-2-4 or 8 points according to event severity. Points are summed up during each treatment period in this study.</description>
  </other_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Infantile Respiratory Distress Syndrome</condition>
  <condition>Ventilator Lung; Newborn</condition>
  <arm_group>
    <arm_group_label>RMC only</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>routine manual control (RMC) of the fraction of inspired oxygen (FIO2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPOCnew and 2s SpO2 averaging</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>routine manual control (RMC) + automatic oxygen control (SPOC) with &quot;new&quot; algorithm of the fraction of inspired oxygen (FIO2).&#xD;
The SpO2 signal averaging time is 2s.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPOCnew and 8s SpO2 averaging</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>routine manual control (RMC) + automatic oxygen control (SPOC) with &quot;new&quot; algorithm of the fraction of inspired oxygen (FIO2).&#xD;
The SpO2 signal averaging time is 8s.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPOCold and 2s SpO2 averaging</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>routine manual control (RMC) + automatic oxygen control (SPOC) with &quot;old&quot; algorithm of the fraction of inspired oxygen (FIO2).&#xD;
The SpO2 signal averaging time is 2s.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPOCold and 8s SpO2 averaging</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>routine manual control (RMC) + automatic oxygen control (SPOC) with &quot;old&quot; algorithm of the fraction of inspired oxygen (FIO2).&#xD;
The SpO2 signal averaging time is 8s.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>SPOCnew</intervention_name>
    <description>SPOC is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (SPO2). The revised &quot;new&quot; algorithm is turned on.</description>
    <arm_group_label>SPOCnew and 2s SpO2 averaging</arm_group_label>
    <arm_group_label>SPOCnew and 8s SpO2 averaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>8s SpO2 averaging</intervention_name>
    <description>The arterial saturation (SPO2) will be averaged over 8s.</description>
    <arm_group_label>SPOCnew and 8s SpO2 averaging</arm_group_label>
    <arm_group_label>SPOCold and 8s SpO2 averaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>SPOCold</intervention_name>
    <description>SPOC is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (SPO2). The former &quot;old&quot; algorithm is turned on.</description>
    <arm_group_label>SPOCold and 2s SpO2 averaging</arm_group_label>
    <arm_group_label>SPOCold and 8s SpO2 averaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>2s SpO2 averaging</intervention_name>
    <description>The arterial saturation (SPO2) will be averaged over 2s.</description>
    <arm_group_label>SPOCnew and 2s SpO2 averaging</arm_group_label>
    <arm_group_label>SPOCold and 2s SpO2 averaging</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  gestational age at birth &lt;34+1/7weeks and&#xD;
&#xD;
          -  invasive mechanical ventilation OR noninvasive ventilation OR continous positive&#xD;
             airway pressure support and&#xD;
&#xD;
          -  Fraction of inspired oxygen above 0.21 before inclusion and&#xD;
&#xD;
          -  more than 2 hypoxaemic events (arterial oxygen saturation below 80%) within 8 hours&#xD;
             before inclusion and&#xD;
&#xD;
          -  parental written informed consent&#xD;
&#xD;
        Exclusion Criteria (any of the following):&#xD;
&#xD;
          -  congenital pulmonary anomalies&#xD;
&#xD;
          -  congenital heart defects influencing SpO2 (i.e. cyanotic heart defects)&#xD;
&#xD;
          -  right-to -left shunt through a PDA&#xD;
&#xD;
          -  Severe neonatal complications during study period (sepsis, necrotising enterocolitis)&#xD;
&#xD;
          -  diaphragmatic hernia or other diaphragmatic disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>34 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christoph E Schwarz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Tubingen, University Hospital, Dept. Neonatology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christoph E Schwarz, MD</last_name>
    <phone>+49707129-0</phone>
    <phone_ext>84742</phone_ext>
    <email>c.schwarz@med.uni-tuebingen.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Axel R Franz, MD</last_name>
    <phone>+49707129-0</phone>
    <phone_ext>83791</phone_ext>
    <email>axel.franz@med.uni-tuebingen.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Neonatology, University Children's Hospital</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christoph E Schwarz, MD</last_name>
      <phone>+49707129-0</phone>
      <phone_ext>80895</phone_ext>
      <email>c.schwarz@med.uni-tuebingen.de</email>
    </contact>
    <contact_backup>
      <last_name>Axel R Franz, MD</last_name>
      <phone>+49707129-0</phone>
      <phone_ext>83791</phone_ext>
      <email>axel.franz@med.uni-tuebingen.de</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
    <mesh_term>Hyaline Membrane Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03785899
org study id: optimalSPOC
nct id: NCT03785899
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Single-center, randomised controlled, cross-over clinical trial in preterm infants born at
      gestational age below 34+1/7 weeks receiving supplemental oxygen and respiratory support
      (continous positive airway pressure (CPAP) or non-invasive ventilation (NIV) or invasive
      ventilation (IV)). Routine manual control (RMC) of the fraction of inspired oxygen (FiO2)
      will be tested against RMC supported by automatic control (SPOC) with "old"-algorithm and RMC
      supported by CLAC with "new"-algorithm.

      The first primary hypothesis is, that the use of the "new" algorithm results in more time
      within arterial oxygen saturation (SpO2) target range compared to RMC only. The a-priori
      subordinate hypothesis is, that the new algorithm results in more time within SpO2 target
      range compared to SPOCold.

      The second primary hypothesis is, that the use of 2 seconds averaging time of the SpO2 Signal
      results in more time within arterial oxygen saturation (SpO2) target range compared to the
      use of 8 seconds averaging interval of the SpO2 signal.
BACKGROUND AND OBJECTIVE In preterm infants receiving supplemental oxygen, routine manual
      control (RMC) of the fraction of inspired oxygen (FiO2) is often difficult and time
      consuming. The investigators developed a system for closed-loop automatic control (SPOC) of
      the FiO2. The objective of this study is to test a revised, "new" algorithm with 3 adaptions
      against the former "old" algorithm and against RMC. The 3 adaptions are:

        1. Faster re-adjustment to baseline-FiO2 (baseline FiO2: mean FiO2 during the previous
           5min)

        2. Delayed reduction of FiO2 below baseline FiO2

        3. Maximum FiO2 adjustable by user

      The first primary hypothesis is, that the application of SPOCnew in addition to RMC results
      in more time within arterial oxygen saturation (SpO2) target range compared to RMC only. The
      a-priori subordinate hypothesis is, that the revised algorithm is more effective as the old
      algorithm to maintain the SpO2 in the target range.

      The second primary hypothesis is, that the shortening of averaging time used for the SpO2
      Signal from 8 seconds to 2 seconds results in more time within SpO2 target range for both,
      SPOCnew and SPOCold.

      Further hypotheses for exploratory testing are, that the SPOC new algorithm will achieve a
      lower proportion of time with SpO2 above and below the target range, hyper- and hypoxia and
      an improved stability of cerebral oxygenation (measured as rcStO2 and rcFtO2E determined by
      Near-infrared spectroscopy) compared with SPOCold and RMC. Reduction of staff workload
      (estimated by number of manual adjustments per hour) by SPOC. Validation of a clinical
      scoring tool to monitor severity of apnea of prematurity.

      STUDY DESIGN The Study is designed as a single-center, randomized controlled, cross-over
      clinical trial in preterm infants receiving mechanical ventilation or nasal continuous
      positive airway pressure or non-invasive ventilation and supplemental oxygen (FiO2 above
      0.21). Within a 30-hour period the investigators will compare 6 hours of RMC with 12-hour
      periods of RMC supported by SPOCnew algorithm or SPOCold algorithm, respectively. During
      intervals with SPOC control the SpO2 Signal averaging time will be 2 second or 8seconds ,
      respectively, for 6 hours each.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of time with SpO2 within target range
time frame: 30 hours
description: Comparison of proportion of time with SpO2 within target range and time above target range if no supplemental oxygen was administered at that time and within the preceding 30sec between the five treatment modalities
measure: Proportion of Time with SpO2 above target range
time frame: 30 hours
description: Comparison of proportion of time with SpO2 above target range if supplemental oxygen was administered at that time or within the preceding 30sec .
measure: Proportion of Time with SpO2 below target range
time frame: 30 hours
description: Comparison of proportion of time with SpO2 below target range.
measure: Proportion of Time with Hypoxia
time frame: 30 hours
description: Comparison of proportion of time with SpO2 below 80%.
measure: Proportion of Time with Hyperoxia
time frame: 30 hours
description: Comparison of proportion of time with SpO2 above 97% if supplemental oxygen was administered at that time or at anytime during the previous 30 seconds.
measure: Stability of cerebral oxygenation
time frame: 30 hours
description: "Area under the curve" of cerebral tissue saturation or fraction of tissue oxygen extraction outside of the infants Median +- 5% or outside of the "safe" interval of 55-80% rcStO2.
measure: Severe hypoxemic episodes
time frame: 30 hours
description: Rate of episodes with SpO2 <80% for at least 60seconds
measure: Staff workload
time frame: 30 hours
description: number of manual adjustments of inspired oxygen per time
measure: Validation of clinical Apnea Score
time frame: 30 hours
description: Validation of a modified Apnea Score monitored by clinical staff by correlation between Score and other secondary outcomes. The modified Apnoea Score aims to quantify the burden from apnoea-bradycardia-syndrome by assigning 1-2-4 or 8 points according to event severity. Points are summed up during each treatment period in this study.
arm group label: RMC only
arm group type: No Intervention
description: routine manual control (RMC) of the fraction of inspired oxygen (FIO2)
arm group label: SPOCnew and 2s SpO2 averaging
arm group type: Experimental
description: routine manual control (RMC) + automatic oxygen control (SPOC) with "new" algorithm of the fraction of inspired oxygen (FIO2).
The SpO2 signal averaging time is 2s.
arm group label: SPOCnew and 8s SpO2 averaging
arm group type: Experimental
description: routine manual control (RMC) + automatic oxygen control (SPOC) with "new" algorithm of the fraction of inspired oxygen (FIO2).
The SpO2 signal averaging time is 8s.
arm group label: SPOCold and 2s SpO2 averaging
arm group type: Active Comparator
description: routine manual control (RMC) + automatic oxygen control (SPOC) with "old" algorithm of the fraction of inspired oxygen (FIO2).
The SpO2 signal averaging time is 2s.
arm group label: SPOCold and 8s SpO2 averaging
arm group type: Active Comparator
description: routine manual control (RMC) + automatic oxygen control (SPOC) with "old" algorithm of the fraction of inspired oxygen (FIO2).
The SpO2 signal averaging time is 8s.
intervention type: Device
intervention name: SPOCnew
description: SPOC is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (SPO2). The revised "new" algorithm is turned on.
arm group label: SPOCnew and 2s SpO2 averaging
arm group label: SPOCnew and 8s SpO2 averaging
intervention type: Device
intervention name: 8s SpO2 averaging
description: The arterial saturation (SPO2) will be averaged over 8s.
arm group label: SPOCnew and 8s SpO2 averaging
arm group label: SPOCold and 8s SpO2 averaging
intervention type: Device
intervention name: SPOCold
description: SPOC is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (SPO2). The former "old" algorithm is turned on.
arm group label: SPOCold and 2s SpO2 averaging
arm group label: SPOCold and 8s SpO2 averaging
intervention type: Device
intervention name: 2s SpO2 averaging
description: The arterial saturation (SPO2) will be averaged over 2s.
arm group label: SPOCnew and 2s SpO2 averaging
arm group label: SPOCold and 2s SpO2 averaging
criteria: 
gender: All
minimum age: N/A
maximum age: 34 Weeks
healthy volunteers: No
last name: Christoph E Schwarz, MD
role: Principal Investigator
affiliation: University of Tubingen, University Hospital, Dept. Neonatology
last name: Christoph E Schwarz, MD
phone: +49707129-0
phone ext: 84742
email: c.schwarz@med.uni-tuebingen.de
last name: Axel R Franz, MD
phone: +49707129-0
phone ext: 83791
email: axel.franz@med.uni-tuebingen.de
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Bronchopulmonary Dysplasia
mesh term: Hyaline Membrane Disease