<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/NCT03785691</url>
  </required_header>
  <id_info>
    <org_study_id>VOMIT</org_study_id>
    <nct_id>NCT03785691</nct_id>
  </id_info>
  <brief_title>Validating the Effect og Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum</brief_title>
  <acronym>VOMIT</acronym>
  <official_title>Validating the Effect of Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum: A Double-Blind Randomised Placebo-Controlled Multicentre Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nordsjaellands Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bispebjerg Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Herlev and Gentofte Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hvidovre University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Regionernes Medicinpulje</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kolding Sygehus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nordsjaellands Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim is to investigate the efficacy of mirtazapine and ondansetron as treatment for&#xD;
      hyperemesis gravidarum(HG).&#xD;
&#xD;
      The setup is a double-blind multicenter trial where patients suffering from HG will be&#xD;
      randomized to treatment with either mirtazapine, ondansetron or placebo (1:1:1).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruiting difficulties&#xD;
  </why_stopped>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Actual">July 31, 2022</completion_date>
  <primary_completion_date type="Actual">July 31, 2022</primary_completion_date>
  <phase>Phase 2</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>Randomized placebo controlled multicenter trial testing already marketed drugs on a new indication.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All oral tablets will be encapsulated in gelatine to ensure identical look, smell and taste.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group.</measure>
    <time_frame>2 days</time_frame>
    <description>Change in Pregnancy Unique Quantification of Emesis 24 score (PUQE-24 score) (patient reported) from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group. PUQE-24 score ranges 3-15 with 3 being better and 15 being worse.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in nausea and vomiting from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.</measure>
    <time_frame>2 days</time_frame>
    <description>Change in PUQE-24 score (patient reported) from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the mirtazapine group versus the placebo group.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-) (long term) in the mirtazapine group versus the placebo group. Only tested if outcome 1 is significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the ondansetron group versus the placebo group.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-) (long term) in the ondansetron group versus the placebo group. Only tested if outcome 2 is significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group.</measure>
    <time_frame>2 days</time_frame>
    <description>Change in PUQE-24 score (patient reported) from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group. Only tested if outcome 1 is significant.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in nausea and vomiting from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall nausea and vomiting during the intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Area under the curve for PUQE-24 score (patient reported) during the intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in well-being during the intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in PUQE well-being score (patient reported) during the intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in nausea during the intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in daily nausea visual analog scale (VAS) (patient reported) during the intervention in the three different groups. VAS score ranges 0-100 with 0 being better and 100 being worse. Numbers are not visible to subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in vomiting during the intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in number of daily vomiting episodes (patient reported) during the intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of side effects in the three different groups.</measure>
    <time_frame>19 days</time_frame>
    <description>Occurrence of side effects (patient reported and registered by trial personnel) during and until 5 days after the intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life for nausea and vomiting during pregnancy from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in Health-Related Quality of Life for Nausea and Vomiting during Pregnancy (NVPQOL) score (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups. NVPQOL score ranges 30-210 with 30 being better and 210 being worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in severity of hyperemesis gravidarum from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in HyperEmesis Level Prediction (HELP) score (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups. HELP score ranges 0-50 with 0 being better and 50 being worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in health-related quality of life from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in health status (EQ-5D-5L) (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in sleep quality from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in modified Pittsburg Sleep Quality Index (PSQI) (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.Modified PSQI score ranges 0-12 with 0 being better and 12 being worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction with treatment Day 7(+/-1) and Day 14(+/-1) in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Patient satisfaction with treatment VAS (patient reported) on Day 7(+/-1) and Day 14(+/-1) in the three different groups. VAS score ranges 0-100 with 0 being better and 100 being worse. Numbers are not visible to subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in patient consideration of termination of pregnancy from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Change in patient consideration of termination of pregnancy (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Request for dosage increase in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Frequency of request for dosage increase in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Request for continuation of trial medication after end of intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Frequency of request for continuation of trial medication after end of intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of rescue medication during the intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Use of rescue medication during (patient reported) the intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days on sick leave during the intervention in the three different groups</measure>
    <time_frame>14 days</time_frame>
    <description>Number of days on sick leave (patient reported) during the intervention in the three different groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Necessity of i.v.-fluids during the intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Amount of treatments with i.v.-fluids during the intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need of hospitalisation during the intervention in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Number of days of hospitalisations during the intervention in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight change from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Weight change in kg from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcome: Live birth, loss or termination of pregnancy</measure>
    <time_frame>8 months</time_frame>
    <description>Live birth, loss or termination of pregnancy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delivery outcome: Mode of delivery</measure>
    <time_frame>8 months</time_frame>
    <description>Mode of delivery: Vaginal, cesarian, vacuum extraction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delivery outcome: Delivery complications</measure>
    <time_frame>8 months</time_frame>
    <description>Eg. postpartum hemorrhage, shoulder dystocia, sphincter rupture</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: birth weight.</measure>
    <time_frame>8 months</time_frame>
    <description>Birth weight in g.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: gestational age at birth.</measure>
    <time_frame>8 months</time_frame>
    <description>Gestational age at birth in weeks plus days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: APGAR score.</measure>
    <time_frame>8 months</time_frame>
    <description>APGAR score at 1, 5 and 10 minutes after birth. APGAR score ranges 0-10 with 0 being worse and 10 being better.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: umbilical cord pH.</measure>
    <time_frame>8 months</time_frame>
    <description>Umbilical cord pH at birth.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: placenta weight.</measure>
    <time_frame>8 months</time_frame>
    <description>placenta weight in g.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: sex.</measure>
    <time_frame>8 months</time_frame>
    <description>offsprings sex.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: hospitalizations on neonatal ward during the first month post-partum.</measure>
    <time_frame>9 months</time_frame>
    <description>Hospitalizations of the offspring in neonatal ward during the first month post-partum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Live birth outcome: congenital malformations (depending on gestational age also registered on early ended pregnancies).</measure>
    <time_frame>8 months</time_frame>
    <description>Congenital malformations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of treatment failure in the three different groups.</measure>
    <time_frame>14 days</time_frame>
    <description>Frequency of and time to treatment failure in the three different groups.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Hyperemesis Gravidarum</condition>
  <condition>Nausea Gravidarum</condition>
  <condition>Vomiting of Pregnancy</condition>
  <arm_group>
    <arm_group_label>Mirtazapine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mirtazapine 15 mg oral tablet (incapsulated in gelatine to provide blinding) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered once daily (morning).&#xD;
On Day 7 dosage increase is optional. If desired, mirtazapine 30 mg oral tablet (incapsulated in gelatine) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered three times daily (morning, noon and late afternoon). In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ondansetron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered twice daily (morning and bedtime) for 7 days.&#xD;
On Day 7 dosage increase is optional. If desired, ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral tablet (empty gelatine capsule) will be administered twice daily (morning and bedtime) for 7 days.&#xD;
On Day 7 dosage increase is optional. If desired, placebo oral tablet (empty gelatine capsule) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mirtazapine</intervention_name>
    <description>Mirtazapine 15 mg oral tablet (incapsulated in gelatine to provide blinding) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered once daily (morning).&#xD;
On Day 7 dosage increase is optional. If desired, mirtazapine 30 mg oral tablet (incapsulated in gelatine) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered three times daily (morning, noon and late afternoon). In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.</description>
    <arm_group_label>Mirtazapine</arm_group_label>
    <other_name>KRKA Mirtazapine Oral Tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ondansetron</intervention_name>
    <description>Ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered twice daily (morning and bedtime) for 7 days.&#xD;
On Day 7 dosage increase is optional. If desired, ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.</description>
    <arm_group_label>Ondansetron</arm_group_label>
    <other_name>Bluefish Ondansetron Oral Tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo oral tablet (empty gelatine capsule) will be administered twice daily (morning and bedtime) for 7 days.&#xD;
On Day 7 dosage increase is optional. If desired, placebo oral tablet (empty gelatine capsule) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo Oral Tablet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent obtained before any trial related procedures are performed&#xD;
&#xD;
          -  Female age &gt;18 years&#xD;
&#xD;
          -  Pregnant woman with gestational age between 5+0 and 19+6&#xD;
&#xD;
          -  Nausea and vomiting without other obvious reason&#xD;
&#xD;
          -  PUQE-24 score ≥13 OR PUQE-24 score ≥7 AND&#xD;
&#xD;
               1. weight loss &gt;5% of pre-pregnancy weight and/or&#xD;
&#xD;
               2. hospitalisation due to nausea and vomiting of pregnancy&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
          -  The subject must be willing and able to comply with trial protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mola pregnancy, multiple gestation or non-vital pregnancy&#xD;
&#xD;
          -  Nausea and vomiting of other aetiology than NVP&#xD;
&#xD;
          -  Allergic to selective 5-HT3-receptor antagonists&#xD;
&#xD;
          -  Ongoing treatment with antidepressant medication&#xD;
&#xD;
          -  Pre-existing diagnosis of chronic kidney disease, diabetes type 1 or 2, significant&#xD;
             cardiac disease (incl. long QT syndrome), epilepsy, HIV. In case of other pre-existing&#xD;
             conditions subjects might be excluded based on individual assessment by an MD&#xD;
&#xD;
          -  Elevated liver enzymes (ALAT&gt;150 U/l)&#xD;
&#xD;
          -  Elevated creatinine (&gt;100 µmol/l)&#xD;
&#xD;
          -  ECG showing long QT-syndrome (QTc &gt;460msek)&#xD;
&#xD;
          -  Weekly alcohol intake &gt;2 units of alcohol&#xD;
&#xD;
          -  Not able to take medicine orally&#xD;
&#xD;
          -  Not able to understand spoken and/or written Danish&#xD;
&#xD;
          -  Participation in another investigational drug trial within current pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne Ostenfeld, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Obstetrics and gynecology, Nordsjællands Hospital Hillerød</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Gynaecology and Obstetrics, Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Gynaecology and Obstetrics, Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Gynaecology and Obstetrics, Herlev Hospital</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Gynaecology and Obstetrics, Nordsjællands Hospital</name>
      <address>
        <city>Hillerød</city>
        <zip>3400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Gynaecology and Obstetrics, Hvidovre Hospital</name>
      <address>
        <city>Hvidovre</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Gynaecology and Obstetrics, Kolding Sygehus</name>
      <address>
        <city>Kolding</city>
        <zip>6000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Gynaecology and Obstetrics, Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>November 13, 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 26, 2023</last_update_submitted>
  <last_update_submitted_qc>January 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nordsjaellands Hospital</investigator_affiliation>
    <investigator_full_name>Anne Ostenfeld</investigator_full_name>
    <investigator_title>MD, PhD student</investigator_title>
  </responsible_party>
  <keyword>Hyperemesis Gravidarum (HG)</keyword>
  <keyword>Mirtazapine</keyword>
  <keyword>Ondansetron</keyword>
  <keyword>Pregnancy</keyword>
  <keyword>Nausea and Vomiting of Pregnancy (NVP)</keyword>
  <keyword>Randomized Controlled Trial (RCT)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperemesis Gravidarum</mesh_term>
    <mesh_term>Nausea</mesh_term>
    <mesh_term>Vomiting</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ondansetron</mesh_term>
    <mesh_term>Mirtazapine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Access to patient level data and supporting clinical documents may be requested. Requests will be reviewed on the basis of methodological proposal. Patient data will be de-identified to protect the privacy of trial patients in line with applicable laws and regulations.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Following publication, no end date.</ipd_time_frame>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol: Current version</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 1, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03785691/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Original version</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03785691/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan: Current version</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 1, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03785691/SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan: Original version</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT03785691/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03785691
org study id: VOMIT
nct id: NCT03785691
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The aim is to investigate the efficacy of mirtazapine and ondansetron as treatment for
      hyperemesis gravidarum(HG).

      The setup is a double-blind multicenter trial where patients suffering from HG will be
      randomized to treatment with either mirtazapine, ondansetron or placebo (1:1:1).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized placebo controlled multicenter trial testing already marketed drugs on a new indication.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All oral tablets will be encapsulated in gelatine to ensure identical look, smell and taste.
measure: Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group.
time frame: 2 days
description: Change in Pregnancy Unique Quantification of Emesis 24 score (PUQE-24 score) (patient reported) from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group. PUQE-24 score ranges 3-15 with 3 being better and 15 being worse.
measure: Change in nausea and vomiting from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.
time frame: 2 days
description: Change in PUQE-24 score (patient reported) from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.
measure: Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the mirtazapine group versus the placebo group.
time frame: 14 days
description: Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-) (long term) in the mirtazapine group versus the placebo group. Only tested if outcome 1 is significant.
measure: Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the ondansetron group versus the placebo group.
time frame: 14 days
description: Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-) (long term) in the ondansetron group versus the placebo group. Only tested if outcome 2 is significant.
measure: Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group.
time frame: 2 days
description: Change in PUQE-24 score (patient reported) from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group. Only tested if outcome 1 is significant.
measure: Change in nausea and vomiting from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.
time frame: 14 days
description: Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.
measure: Overall nausea and vomiting during the intervention in the three different groups.
time frame: 14 days
description: Area under the curve for PUQE-24 score (patient reported) during the intervention in the three different groups.
measure: Change in well-being during the intervention in the three different groups.
time frame: 14 days
description: Change in PUQE well-being score (patient reported) during the intervention in the three different groups.
measure: Change in nausea during the intervention in the three different groups.
time frame: 14 days
description: Change in daily nausea visual analog scale (VAS) (patient reported) during the intervention in the three different groups. VAS score ranges 0-100 with 0 being better and 100 being worse. Numbers are not visible to subjects.
measure: Change in vomiting during the intervention in the three different groups.
time frame: 14 days
description: Change in number of daily vomiting episodes (patient reported) during the intervention in the three different groups.
measure: Occurrence of side effects in the three different groups.
time frame: 19 days
description: Occurrence of side effects (patient reported and registered by trial personnel) during and until 5 days after the intervention in the three different groups.
measure: Change in quality of life for nausea and vomiting during pregnancy from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
time frame: 14 days
description: Change in Health-Related Quality of Life for Nausea and Vomiting during Pregnancy (NVPQOL) score (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups. NVPQOL score ranges 30-210 with 30 being better and 210 being worse.
measure: Change in severity of hyperemesis gravidarum from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
time frame: 14 days
description: Change in HyperEmesis Level Prediction (HELP) score (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups. HELP score ranges 0-50 with 0 being better and 50 being worse.
measure: Change in health-related quality of life from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
time frame: 14 days
description: Change in health status (EQ-5D-5L) (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
measure: Change in sleep quality from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
time frame: 14 days
description: Change in modified Pittsburg Sleep Quality Index (PSQI) (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.Modified PSQI score ranges 0-12 with 0 being better and 12 being worse.
measure: Patient satisfaction with treatment Day 7(+/-1) and Day 14(+/-1) in the three different groups.
time frame: 14 days
description: Patient satisfaction with treatment VAS (patient reported) on Day 7(+/-1) and Day 14(+/-1) in the three different groups. VAS score ranges 0-100 with 0 being better and 100 being worse. Numbers are not visible to subjects.
measure: Change in patient consideration of termination of pregnancy from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
time frame: 14 days
description: Change in patient consideration of termination of pregnancy (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
measure: Request for dosage increase in the three different groups.
time frame: 14 days
description: Frequency of request for dosage increase in the three different groups.
measure: Request for continuation of trial medication after end of intervention in the three different groups.
time frame: 14 days
description: Frequency of request for continuation of trial medication after end of intervention in the three different groups.
measure: Use of rescue medication during the intervention in the three different groups.
time frame: 14 days
description: Use of rescue medication during (patient reported) the intervention in the three different groups.
measure: Number of days on sick leave during the intervention in the three different groups
time frame: 14 days
description: Number of days on sick leave (patient reported) during the intervention in the three different groups
measure: Necessity of i.v.-fluids during the intervention in the three different groups.
time frame: 14 days
description: Amount of treatments with i.v.-fluids during the intervention in the three different groups.
measure: Need of hospitalisation during the intervention in the three different groups.
time frame: 14 days
description: Number of days of hospitalisations during the intervention in the three different groups.
measure: Weight change from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
time frame: 14 days
description: Weight change in kg from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
measure: Pregnancy outcome: Live birth, loss or termination of pregnancy
time frame: 8 months
description: Live birth, loss or termination of pregnancy.
measure: Delivery outcome: Mode of delivery
time frame: 8 months
description: Mode of delivery: Vaginal, cesarian, vacuum extraction.
measure: Delivery outcome: Delivery complications
time frame: 8 months
description: Eg. postpartum hemorrhage, shoulder dystocia, sphincter rupture
measure: Live birth outcome: birth weight.
time frame: 8 months
description: Birth weight in g.
measure: Live birth outcome: gestational age at birth.
time frame: 8 months
description: Gestational age at birth in weeks plus days.
measure: Live birth outcome: APGAR score.
time frame: 8 months
description: APGAR score at 1, 5 and 10 minutes after birth. APGAR score ranges 0-10 with 0 being worse and 10 being better.
measure: Live birth outcome: umbilical cord pH.
time frame: 8 months
description: Umbilical cord pH at birth.
measure: Live birth outcome: placenta weight.
time frame: 8 months
description: placenta weight in g.
measure: Live birth outcome: sex.
time frame: 8 months
description: offsprings sex.
measure: Live birth outcome: hospitalizations on neonatal ward during the first month post-partum.
time frame: 9 months
description: Hospitalizations of the offspring in neonatal ward during the first month post-partum.
measure: Live birth outcome: congenital malformations (depending on gestational age also registered on early ended pregnancies).
time frame: 8 months
description: Congenital malformations.
measure: Occurrence of treatment failure in the three different groups.
time frame: 14 days
description: Frequency of and time to treatment failure in the three different groups.
arm group label: Mirtazapine
arm group type: Experimental
description: Mirtazapine 15 mg oral tablet (incapsulated in gelatine to provide blinding) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered once daily (morning).
On Day 7 dosage increase is optional. If desired, mirtazapine 30 mg oral tablet (incapsulated in gelatine) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered three times daily (morning, noon and late afternoon). In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
arm group label: Ondansetron
arm group type: Experimental
description: Ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered twice daily (morning and bedtime) for 7 days.
On Day 7 dosage increase is optional. If desired, ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo oral tablet (empty gelatine capsule) will be administered twice daily (morning and bedtime) for 7 days.
On Day 7 dosage increase is optional. If desired, placebo oral tablet (empty gelatine capsule) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
intervention type: Drug
intervention name: Mirtazapine
description: Mirtazapine 15 mg oral tablet (incapsulated in gelatine to provide blinding) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered once daily (morning).
On Day 7 dosage increase is optional. If desired, mirtazapine 30 mg oral tablet (incapsulated in gelatine) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered three times daily (morning, noon and late afternoon). In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
arm group label: Mirtazapine
other name: KRKA Mirtazapine Oral Tablet
intervention type: Drug
intervention name: Ondansetron
description: Ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered twice daily (morning and bedtime) for 7 days.
On Day 7 dosage increase is optional. If desired, ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
arm group label: Ondansetron
other name: Bluefish Ondansetron Oral Tablet
intervention type: Drug
intervention name: Placebo
description: Placebo oral tablet (empty gelatine capsule) will be administered twice daily (morning and bedtime) for 7 days.
On Day 7 dosage increase is optional. If desired, placebo oral tablet (empty gelatine capsule) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
arm group label: Placebo
other name: Placebo Oral Tablet
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Anne Ostenfeld, MD
role: Principal Investigator
affiliation: Department of Obstetrics and gynecology, Nordsjællands Hospital Hillerød
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Nordsjaellands Hospital
investigator full name: Anne Ostenfeld
investigator title: MD, PhD student
mesh term: Hyperemesis Gravidarum
mesh term: Nausea
mesh term: Vomiting
mesh term: Ondansetron
mesh term: Mirtazapine
sharing ipd: Yes
ipd description: Access to patient level data and supporting clinical documents may be requested. Requests will be reviewed on the basis of methodological proposal. Patient data will be de-identified to protect the privacy of trial patients in line with applicable laws and regulations.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Following publication, no end date.
provided document: 
provided document: 
provided document: 
provided document: 