xml: <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/NCT06010238</url>
    </required_header>
    <id_info>
      <org_study_id>84591</org_study_id>
      <nct_id>NCT06010238</nct_id>
    </id_info>
    <brief_title>STV Analysis Versus Visual Evaluation of Cardiotocography in FGR</brief_title>
    <acronym>SAVEFGR</acronym>
    <official_title>Short Term Variation Analysis Versus Visual Evaluation of Cardiotocography in Fetal Growth Restriction</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</source>
    <oversight_info>
      <has_dmc>Yes</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>
        This stepped wedge cluster randomized clinical trial investigates whether in pregnant women&#xD;
        with severe, early-onset fetal growth restriction, the use of STV analysis in fetal&#xD;
        monitoring improves the chances of perinatal survival, compared with visual evaluation of the&#xD;
        cardiotocography.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Severe, early-onset fetal growth restriction (FGR, &lt;32 weeks gestation) is a condition in&#xD;
        which the fetus does not reach its growth potential due to placental insufficiency[. This&#xD;
        condition affects about 0.3% of pregnancies, accounting for an estimated 15,000 babies in&#xD;
        Europe being born premature below 32 weeks gestation. The main clinical dilemma of FGR lies&#xD;
        in the timing of birth, given the balance of risks of antenatal mortality and severe damage&#xD;
        to organs and the aggravated neonatal effects of prematurity: death or survival with severe&#xD;
        neurodevelopmental impairment. The mainstay of clinical management in these cases pivots&#xD;
        around the anticipation of the risk of fetal demise from placental oxygenation failure. The&#xD;
        monitoring variables that are currently available comprise assessment of the severity of&#xD;
        metabolic insufficiency (fetal size and growth, Doppler ultrasound, serum biomarkers) and the&#xD;
        early detection of progressive fetal hypoxia with cardiotocography (CTG). The common approach&#xD;
        is to deliver the fetus when signs of advanced hypoxia appear on CTG. A delicate balance&#xD;
        exists between having the fetus born (too) early and facing the risks of extreme prematurity&#xD;
        combined with a very low birthweight; and between delivering the fetus (too) late when the&#xD;
        fetus has the disadvantage of hypoxia at birth. The decision when to deliver the fetus, is&#xD;
        made mostly based on the CTG. The inter- and intra-observer variability could be overcome by&#xD;
        software analysis according to the original Dawes&amp;Redman algorithm. The software calculates&#xD;
        the short-term variation (STV) of the inter-beat interval expressed in milliseconds, and a&#xD;
        range of secondary calculations. In contrast with repeated decelerations, when fetal hypoxia&#xD;
        is considered evident, the place of the software analysis of the fetal heart rate variability&#xD;
        is less clear. Although the advantages of mathematized and uniform quantification of the&#xD;
        fetal heart rate variability appear self-evident, there are no studies with sufficient power&#xD;
        to detect an association of intervention based on STV at any threshold with the most&#xD;
        important outcomes: fetal death and long-term infant outcome.&#xD;
  &#xD;
        The purpose of this study is to assess the outcomes of monitoring the fetal condition with&#xD;
        STV in cCTG compared to visual interpretation of the CTG in order to time delivery in&#xD;
        pregnant women with severe, early-onset FGR.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">January 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">January 1, 2027</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>Parallel Assignment</intervention_model>
      <intervention_model_description>Stepped wedge cluster randomized clinical trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Proportion of pregnancies resulting in perinatal death</measure>
      <time_frame>Before discharge from NICU, up to 1 year</time_frame>
      <description>Perinatal death is defined as antenatal death or neonatal/infant death before discharge from NICU</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of children with major neonatal morbidity</measure>
      <time_frame>Before discharge from NICU, up to 1 year</time_frame>
      <description>Major neonatal morbidity is a composite outcome defined as intraventricular hemorrhage grade 3 or more, periventricular leukomalacia grade 2 or more, moderate or severe bronchopulmonary dysplasia, necrotizing enterocolitis Bell stage 2 or more, or retinopathy of prematurity requiring therapy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of children with neonatal morbidities</measure>
      <time_frame>Before discharge from NICU, up to 1 year</time_frame>
      <description>Individual neonatal morbidities of the abovementioned composite outcome and additionally persisting ductus arteriosus, persistent pulmonary hypertension of the newborn (PPHN), respiratory distress syndrome (RDS), period of invasive mechanical ventilation in days, medication need, hypoglycaemia, neonatal jaundice, sepsis and cardiovascular function.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of children with neurodevelopmental impairment</measure>
      <time_frame>At two years of corrected age</time_frame>
      <description>Neurodevelopmental impairment is defined as an abnormal test on Bayley III Dutch version (or version IV if available) (composite cognitive score &lt; 85, composite motor score &lt; 85), cerebral palsy, with a Gross Motor Function Classification System (GMFCS) grade &gt; 1, hearing loss needing hearing aids, or severe visual loss (legally certifiable as blind or partially sighted) assessed at two years of corrected age</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">800</enrollment>
    <condition>Fetal Growth Retardation</condition>
    <arm_group>
      <arm_group_label>Visual interpretation of cardiotocography</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Monitoring by visual interpretation of cardiotocography</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Short term variation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Short term variation by computer software analysis</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Short term variation</intervention_name>
      <description>Short term variation in computer software analysis</description>
      <arm_group_label>Short term variation</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Visual interpretation</intervention_name>
      <description>Visual interpretation of cardiotocography</description>
      <arm_group_label>Visual interpretation of cardiotocography</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Pregnant women with a singleton pregnancy between 24 weeks and 0 days and 31 weeks and&#xD;
               6 days with severe, early-onset fetal growth restriction, admitted in hospital or&#xD;
               frequently evaluated ambulatory by CTG (according to local protocol) for fetal&#xD;
               monitoring.&#xD;
  &#xD;
            -  Fetal growth restriction is defined in line with the international Delphi consensus as&#xD;
               biometric ultrasound measurement of the abdominal circumference (AC) OR a combination&#xD;
               of measurements resulting in an estimated fetal weight (EFW) below the 3rd percentile&#xD;
               (&lt;p3) OR a combination of EFW &lt;p10 AND uterine artery pulsatility index (PI) &gt;p95 OR&#xD;
               umbilical artery Doppler PI &gt;p95.&#xD;
  &#xD;
            -  Maternal age ≥ 18 years.&#xD;
  &#xD;
            -  Able to provide written informed consent for collection and use of data on informed&#xD;
               consent form in available language.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Known congenital or chromosomal anomalies influencing perinatal outcome.&#xD;
  &#xD;
            -  Imminent labour or expected maternal indication for delivery &lt; 48 hours.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Wessel Ganzevoort, MD PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Wessel Ganzevoort, MD PhD</last_name>
      <phone>003120-5669111</phone>
      <email>j.w.ganzevoort@amsterdamumc.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Anouk Pels, MD PhD</last_name>
      <phone>003120-5669111</phone>
      <email>a.pels@amsterdamumc.nl</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</investigator_affiliation>
      <investigator_full_name>Wessel Ganzevoort</investigator_full_name>
      <investigator_title>Principal investigator</investigator_title>
    </responsible_party>
    <keyword>fetal growth restriction</keyword>
    <keyword>cardiotocography</keyword>
    <keyword>perinatal death</keyword>
    <keyword>short term variation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Fetal Growth Retardation</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>There is no current plan, but data will be available upon collaboration request</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06010238
  org study id: 84591
  nct id: NCT06010238
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This stepped wedge cluster randomized clinical trial investigates whether in pregnant women
        with severe, early-onset fetal growth restriction, the use of STV analysis in fetal
        monitoring improves the chances of perinatal survival, compared with visual evaluation of the
        cardiotocography.
  Severe, early-onset fetal growth restriction (FGR, <32 weeks gestation) is a condition in
        which the fetus does not reach its growth potential due to placental insufficiency[. This
        condition affects about 0.3% of pregnancies, accounting for an estimated 15,000 babies in
        Europe being born premature below 32 weeks gestation. The main clinical dilemma of FGR lies
        in the timing of birth, given the balance of risks of antenatal mortality and severe damage
        to organs and the aggravated neonatal effects of prematurity: death or survival with severe
        neurodevelopmental impairment. The mainstay of clinical management in these cases pivots
        around the anticipation of the risk of fetal demise from placental oxygenation failure. The
        monitoring variables that are currently available comprise assessment of the severity of
        metabolic insufficiency (fetal size and growth, Doppler ultrasound, serum biomarkers) and the
        early detection of progressive fetal hypoxia with cardiotocography (CTG). The common approach
        is to deliver the fetus when signs of advanced hypoxia appear on CTG. A delicate balance
        exists between having the fetus born (too) early and facing the risks of extreme prematurity
        combined with a very low birthweight; and between delivering the fetus (too) late when the
        fetus has the disadvantage of hypoxia at birth. The decision when to deliver the fetus, is
        made mostly based on the CTG. The inter- and intra-observer variability could be overcome by
        software analysis according to the original Dawes&Redman algorithm. The software calculates
        the short-term variation (STV) of the inter-beat interval expressed in milliseconds, and a
        range of secondary calculations. In contrast with repeated decelerations, when fetal hypoxia
        is considered evident, the place of the software analysis of the fetal heart rate variability
        is less clear. Although the advantages of mathematized and uniform quantification of the
        fetal heart rate variability appear self-evident, there are no studies with sufficient power
        to detect an association of intervention based on STV at any threshold with the most
        important outcomes: fetal death and long-term infant outcome.
  
        The purpose of this study is to assess the outcomes of monitoring the fetal condition with
        STV in cCTG compared to visual interpretation of the CTG in order to time delivery in
        pregnant women with severe, early-onset FGR.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Stepped wedge cluster randomized clinical trial
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Proportion of pregnancies resulting in perinatal death
  time frame: Before discharge from NICU, up to 1 year
  description: Perinatal death is defined as antenatal death or neonatal/infant death before discharge from NICU
  measure: Proportion of children with major neonatal morbidity
  time frame: Before discharge from NICU, up to 1 year
  description: Major neonatal morbidity is a composite outcome defined as intraventricular hemorrhage grade 3 or more, periventricular leukomalacia grade 2 or more, moderate or severe bronchopulmonary dysplasia, necrotizing enterocolitis Bell stage 2 or more, or retinopathy of prematurity requiring therapy.
  measure: Proportion of children with neonatal morbidities
  time frame: Before discharge from NICU, up to 1 year
  description: Individual neonatal morbidities of the abovementioned composite outcome and additionally persisting ductus arteriosus, persistent pulmonary hypertension of the newborn (PPHN), respiratory distress syndrome (RDS), period of invasive mechanical ventilation in days, medication need, hypoglycaemia, neonatal jaundice, sepsis and cardiovascular function.
  measure: Proportion of children with neurodevelopmental impairment
  time frame: At two years of corrected age
  description: Neurodevelopmental impairment is defined as an abnormal test on Bayley III Dutch version (or version IV if available) (composite cognitive score < 85, composite motor score < 85), cerebral palsy, with a Gross Motor Function Classification System (GMFCS) grade > 1, hearing loss needing hearing aids, or severe visual loss (legally certifiable as blind or partially sighted) assessed at two years of corrected age
  arm group label: Visual interpretation of cardiotocography
  arm group type: Active Comparator
  description: Monitoring by visual interpretation of cardiotocography
  arm group label: Short term variation
  arm group type: Experimental
  description: Short term variation by computer software analysis
  intervention type: Device
  intervention name: Short term variation
  description: Short term variation in computer software analysis
  arm group label: Short term variation
  intervention type: Device
  intervention name: Visual interpretation
  description: Visual interpretation of cardiotocography
  arm group label: Visual interpretation of cardiotocography
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: 99 Years
  healthy volunteers: No
  last name: Wessel Ganzevoort, MD PhD
  role: Principal Investigator
  affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  last name: Wessel Ganzevoort, MD PhD
  phone: 003120-5669111
  email: j.w.ganzevoort@amsterdamumc.nl
  last name: Anouk Pels, MD PhD
  phone: 003120-5669111
  email: a.pels@amsterdamumc.nl
  responsible party type: Principal Investigator
  investigator affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  investigator full name: Wessel Ganzevoort
  investigator title: Principal investigator
  mesh term: Fetal Growth Retardation
  sharing ipd: No
  ipd description: There is no current plan, but data will be available upon collaboration request