<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/NCT04401384</url>
  </required_header>
  <id_info>
    <org_study_id>NVPAct</org_study_id>
    <nct_id>NCT04401384</nct_id>
  </id_info>
  <brief_title>Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy</brief_title>
  <official_title>Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy: A Randomized Controlled Two-by-two Factorial Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xiaoke Wu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ningxia Hui Autonomous Region Hospital of TCM</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jiangxi Maternal and Child Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jixi Maternal and Child Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Luoyang Hospital of TCM</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xuzhou Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Heilongjiang Chinese Medicine University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shuangyashan Maternal and Child Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Heilongjiang provincial hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jiamusi Maternal and Child Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hegang Maternal and Child Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Suihua Maternal and Child Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mudanjaing Maternal and Child Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Affiliated Hospital of Jiamusi Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Heilongjiang University of Chinese Medicine</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>
      Nausea and vomiting in pregnancy (NVP) is one of the most common symptoms of pregnancy&#xD;
      affecting 50-85% of women during the first half of pregnancy. Maternal morbidity is common&#xD;
      and includes psychological effects, financial burden, clinical complications from nutritional&#xD;
      deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. As the main&#xD;
      means of alternative treatment, economical and easy to obtain; the clinical efficacy of&#xD;
      acupuncture treatment of this disease has low level of evidence and needs to be reconfirmed.&#xD;
      Doxylamine vitamin B6 sustained release tablets (Diclectin, combination of doxylamine&#xD;
      succinate (10mg) and pyridoxine hydrochloride (10mg) are The American College of&#xD;
      Obstetricians and Gynecologists recommends with Level A evidence the use of vitamin B6 in&#xD;
      combination with doxylamine as first-line pharmacotherapy for treatment of NVP. The efficacy&#xD;
      and safety of Diclectin has been confirmed in many years of research, but there is no&#xD;
      evidence of high-level evidence-based medicine for the Chinese population. The purpose of&#xD;
      this multicenter, randomized, double-blind, placebo-controlled trial was to investigate the&#xD;
      efficacy and safety of acupuncture versus Diclectin in the treatment of NVP. We hypothesis&#xD;
      that: (1)Sham acupuncture and Diclectin (Arm B) is more effective than sham acupuncture and&#xD;
      placebo (Arm D); (2)Active acupuncture and placebo (Arm C) is more effective than sham&#xD;
      acupuncture and placebo (Arm D); (3) There is no interaction (either synergistic or&#xD;
      antagonistic effects) between the two interventions of active acupuncture and Diclectin in&#xD;
      patients with NVP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will be randomized into one of the four treatment arms: A) active acupuncture (30&#xD;
      min /every day) + Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine&#xD;
      hydrochloride (10 mg) , 2-4 tablets/day); B) sham acupuncture (30 min /every day) + Diclectin&#xD;
      (2-4 tablets/day); C) active acupuncture (30 min / every day) + Diclectin placebo (2-4&#xD;
      tablets/day); D) sham acupuncture (30 min /every day) + Diclectin placebo (2-4 tablets/day).&#xD;
      Participants will receive active acupuncture or sham acupuncture treatment daily, 14 times in&#xD;
      total, and receive Diclectin or placebo treatment every day (2 tablets at bedtime for the&#xD;
      first two days, if the symptoms are unrelieved, add one tablet in the morning, if the&#xD;
      symptoms are still unrelieved, add another one tablet at three o 'clock in the afternoon) for&#xD;
      2 consecutive weeks, 28-56 tablets in total. Daily measurement PUQE score, Visual analog&#xD;
      scale (VAS), Adverse events and concomitant medications. Weekly visits will include global&#xD;
      assessment of well being, adverse events and concomitant medications. The visit after&#xD;
      treatment will assess NVP quality of life (NVPQoL), SAS, SDS and so on. Participants will be&#xD;
      followed up 30 days after treatment. Primary outcomes is difference of the mean change in&#xD;
      PUQE score from baseline to the last visit. Secondary outcomes were some core outcome set for&#xD;
      hyperemesis gravidarum, including weight difference, quality of life (change in Global&#xD;
      assessment of well-being, NVPQOL, VAS, SDS and SAS), pregnancy complication, treatment&#xD;
      compliance, neonatal outcomes; area under the curve of PUQE score, effect of intervention on&#xD;
      PUQE score reduction over treatment period and adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 21, 2020</start_date>
  <completion_date type="Actual">January 31, 2022</completion_date>
  <primary_completion_date type="Actual">June 23, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <intervention_model_description>Two by two factorial design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15</measure>
    <time_frame>Baseline to day 15; Scores ranged 3 to 15, with higher scores indicating more</time_frame>
    <description>Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Score change of maternal weight from baseline to the last visit</measure>
    <time_frame>Baseline to day 15; no range of variation</time_frame>
    <description>Score change of maternal weight from baseline to the last visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (sodium)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (potassium)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (calcium)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (chlorine)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (phosphorus)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (magnesium)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (iron)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: μmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of electrolyte index (zinc)</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: μmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of AST</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: U/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of ALT</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: U/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of ALP</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: U/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of creatinine</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: μmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of urea</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of TSH</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: mIU/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of free triiodothyronine</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: pmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of free thyroxine</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: pmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of vitamin b1</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of vitamin b6</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of vitamin b12</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of cortisol</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ug/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of ghrelin</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of leptin</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of 5-hydroxytryptamine</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of substance P</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: pg/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of arginine vasopressin plasma</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: pg/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of GDF 15</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: pg/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of IGFBP 7</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Value changes from baseline to last Visit. Unit: ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intravenous fluid treatment during treatment</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Intravenous fluid treatment during treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concomitant treatment</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Concomitant treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital admission during treatment</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Hospital admission during treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Termination of pregnancy</measure>
    <time_frame>Data collected from baseline to the end of follow-up period (four weeks after the end of treatment).</time_frame>
    <description>Termination of pregnancy. If the patient is suffering further aggravation of hyperemesis gravidarum, the termination of a wanted pregnancy will be done due to life in danger. Or congenital anomalies are found by ultrasound, the termination of a wanted pregnancy will be done.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal outcomes</measure>
    <time_frame>Data collected from baseline to 42 days after postpartum.</time_frame>
    <description>Including pregnancy complications, termination of pregnancy and birth outcomes. Pregnancy complications including miscarriage (in the first trimester and in the second trimester), hypertensive disorders, and gestational diabetes; birth outcomes including live birth, vaginal delivery, cesarean section, gestational age, preterm, birth weight and small for gestational age.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction with treatment</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Such as loss of confidence or intolerance to daily acupuncture and so on</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment compliance</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Such as the percentage of drug or needle used; or drug tablets or acupuncture sessions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Offspring outcomes</measure>
    <time_frame>Data collected from baseline to to 42 days after postpartum.</time_frame>
    <description>Including fetal and neonatal congenital anomalies, fetal and neonatal mortality, neonatal hypoglycemia and NICU admission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of PUQE score over treatment</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Scores ranged 3 to 15, with higher scores indicating more severe NVP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PUQE score reduction based on different TCM patterns</measure>
    <time_frame>Scores ranged 3 to 15, with higher reduction indicating the better</time_frame>
    <description>PUQE score reduction based on different TCM patterns</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events and serious adverse events</measure>
    <time_frame>Baseline to the end of follow-up (four weeks after the end of treatment)</time_frame>
    <description>The percentage of adverse events and serious adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: NVPQoL</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Range 30-210, high being poor QoL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: VAS</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Ranged 0-10, high being more severe symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: SDS</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Range 25-10, high being more severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: SAS</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Range 25-100, high being more severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: global assessment of well-being</measure>
    <time_frame>Baseline to day 15</time_frame>
    <description>Range 0-10, low being more severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PUQE score reduction at different levels of NVP</measure>
    <time_frame>Scores ranged 3 to 15, with higher reduction indicating the better</time_frame>
    <description>PUQE score reduction at different levels of NVP</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">352</enrollment>
  <condition>Nausea and Vomiting of Pregnancy</condition>
  <arm_group>
    <arm_group_label>Diclectin plus active acupuncture</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day) + active acupuncture (30 min /every day).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diclectin plus sham acupuncture</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), 2-4 tablets/day) + sham acupuncture (30 min /every day).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo plus active acupuncture</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo plus sham acupuncture</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diclectin</intervention_name>
    <description>Diclectin (combination of 10 mg doxylamine and 10 mg pyridoxine hydrochloride in a delayed release tablet) During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of Diclectin or placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.</description>
    <arm_group_label>Diclectin plus active acupuncture</arm_group_label>
    <arm_group_label>Diclectin plus sham acupuncture</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diclectin placebo</intervention_name>
    <description>Diclectin placebo will be packed and tested by a commercial pharmacy supply company specifically for this study. It have the same appearance, size, batch, odor, and taste compared with Diclectin. During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.</description>
    <arm_group_label>Placebo plus active acupuncture</arm_group_label>
    <arm_group_label>Placebo plus sham acupuncture</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active acupuncture</intervention_name>
    <description>Participants will receive active acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).</description>
    <arm_group_label>Diclectin plus active acupuncture</arm_group_label>
    <arm_group_label>Placebo plus active acupuncture</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham acupuncture</intervention_name>
    <description>Blunt-tipped placebo needles will be used. Participants will receive sham acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6). Then, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).</description>
    <arm_group_label>Diclectin plus sham acupuncture</arm_group_label>
    <arm_group_label>Placebo plus sham acupuncture</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women with 20-45 years of age;&#xD;
&#xD;
          2. PUQE score ≥6;&#xD;
&#xD;
          3. 7-14 weeks of gestation with viable fetus inside the uterine cavity confirmed by&#xD;
             ultrasound dating;&#xD;
&#xD;
          4. Less than 20% weight loss.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Having major medical problems such as malignant tumor, acute or subacute severe&#xD;
             hepatitis, severe aplastic anemia, idiopathic thrombocytopenic purpura, acute&#xD;
             appendicitis, acute pancreatitis, TORCH syndrome, etc&#xD;
&#xD;
          2. Having chronic medical conditions such as poorly controlled diabetes, coronary heart&#xD;
             disease, uncontrolled hypertension, etc&#xD;
&#xD;
          3. Coexistence of other diseases that cause vomiting such as infectious disease,&#xD;
             gestational trophoblastic disease, etc&#xD;
&#xD;
          4. Having asthma, increased intraocular pressure, narrow-angle glaucoma, narrow peptic&#xD;
             ulcer, pyloric obstruction, bladder neck obstruction, etc&#xD;
&#xD;
          5. Taking antiemetics such as vitamin B6, ondansetron, metoclopramide, prednisone,&#xD;
             anti-vomiting Chinese medicine, etc., within the past week&#xD;
&#xD;
          6. Receiving conservative treatment such as dietary and lifestyle modification&#xD;
&#xD;
          7. Abnormal physical examination and laboratory tests (minor abnormalities in laboratory&#xD;
             tests due to pregnancy vomiting, such as liver function and ions, are acceptable for&#xD;
             inclusion)&#xD;
&#xD;
          8. Having mental handicaps or psychological disorders&#xD;
&#xD;
          9. Allergic to doxylamine, other ethanolamine-derived antihistamines, pyridoxine&#xD;
             hydrochloride, or any inactive ingredient in diclectin&#xD;
&#xD;
         10. Using monoamine oxidase inhibitors&#xD;
&#xD;
         11. Driving or operating heavy machinery&#xD;
&#xD;
         12. Using alcohol or other central nervous system inhibitors&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiaoke Wu, Ph.D</last_name>
    <role>Study Chair</role>
    <affiliation>First Affiliated Hospital of Heilongjiang University of Chinese Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>First Affiliated Hospital of Heilongjiang Chinese Medicine University</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heilongjiang provincial hospital</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hegang Maternal and Child Health Hospital</name>
      <address>
        <city>Hegang</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Affiliated Hospital of Jiamusi Medical University</name>
      <address>
        <city>Jiamusi</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiamusi Maternal and Child Health Hospital</name>
      <address>
        <city>Jiamusi</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jixi Maternal and Child Health Hospital</name>
      <address>
        <city>Jixi</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mudanjaing Maternal and Child Health Hospital</name>
      <address>
        <city>Mudanjiang</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shuangyashan Maternal and Child Health Hospital</name>
      <address>
        <city>Shuangyashan</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suihua Maternal and Child Health Hospital</name>
      <address>
        <city>Suihua</city>
        <state>Heilongjing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Luoyang Hospital of TCM</name>
      <address>
        <city>Luoyang</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xuzhou Central Hospital</name>
      <address>
        <city>Xuzhou</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangxi Maternal and Child Health Hospital</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ningxia Hui Autonomous Region Hospital of TCM</name>
      <address>
        <city>Yinchuan</city>
        <state>Ningxia Hui Autonomous Region</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 18, 2020</study_first_submitted>
  <study_first_submitted_qc>May 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>March 31, 2022</last_update_submitted>
  <last_update_submitted_qc>March 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Heilongjiang University of Chinese Medicine</investigator_affiliation>
    <investigator_full_name>Xiaoke Wu</investigator_full_name>
    <investigator_title>Director of obstetrics and Gynecology Department</investigator_title>
  </responsible_party>
  <keyword>Nausea and Vomiting of Pregnancy</keyword>
  <keyword>PUQE</keyword>
  <keyword>Acupuncture</keyword>
  <keyword>Diclectin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Pyridoxine</mesh_term>
    <mesh_term>Dicyclomine, doxylamine, pyridoxine drug combination</mesh_term>
    <mesh_term>Doxylamine</mesh_term>
    <mesh_term>Dicyclomine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04401384
org study id: NVPAct
nct id: NCT04401384
lead sponsor: 
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has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Nausea and vomiting in pregnancy (NVP) is one of the most common symptoms of pregnancy
      affecting 50-85% of women during the first half of pregnancy. Maternal morbidity is common
      and includes psychological effects, financial burden, clinical complications from nutritional
      deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. As the main
      means of alternative treatment, economical and easy to obtain; the clinical efficacy of
      acupuncture treatment of this disease has low level of evidence and needs to be reconfirmed.
      Doxylamine vitamin B6 sustained release tablets (Diclectin, combination of doxylamine
      succinate (10mg) and pyridoxine hydrochloride (10mg) are The American College of
      Obstetricians and Gynecologists recommends with Level A evidence the use of vitamin B6 in
      combination with doxylamine as first-line pharmacotherapy for treatment of NVP. The efficacy
      and safety of Diclectin has been confirmed in many years of research, but there is no
      evidence of high-level evidence-based medicine for the Chinese population. The purpose of
      this multicenter, randomized, double-blind, placebo-controlled trial was to investigate the
      efficacy and safety of acupuncture versus Diclectin in the treatment of NVP. We hypothesis
      that: (1)Sham acupuncture and Diclectin (Arm B) is more effective than sham acupuncture and
      placebo (Arm D); (2)Active acupuncture and placebo (Arm C) is more effective than sham
      acupuncture and placebo (Arm D); (3) There is no interaction (either synergistic or
      antagonistic effects) between the two interventions of active acupuncture and Diclectin in
      patients with NVP.
Subjects will be randomized into one of the four treatment arms: A) active acupuncture (30
      min /every day) + Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine
      hydrochloride (10 mg) , 2-4 tablets/day); B) sham acupuncture (30 min /every day) + Diclectin
      (2-4 tablets/day); C) active acupuncture (30 min / every day) + Diclectin placebo (2-4
      tablets/day); D) sham acupuncture (30 min /every day) + Diclectin placebo (2-4 tablets/day).
      Participants will receive active acupuncture or sham acupuncture treatment daily, 14 times in
      total, and receive Diclectin or placebo treatment every day (2 tablets at bedtime for the
      first two days, if the symptoms are unrelieved, add one tablet in the morning, if the
      symptoms are still unrelieved, add another one tablet at three o 'clock in the afternoon) for
      2 consecutive weeks, 28-56 tablets in total. Daily measurement PUQE score, Visual analog
      scale (VAS), Adverse events and concomitant medications. Weekly visits will include global
      assessment of well being, adverse events and concomitant medications. The visit after
      treatment will assess NVP quality of life (NVPQoL), SAS, SDS and so on. Participants will be
      followed up 30 days after treatment. Primary outcomes is difference of the mean change in
      PUQE score from baseline to the last visit. Secondary outcomes were some core outcome set for
      hyperemesis gravidarum, including weight difference, quality of life (change in Global
      assessment of well-being, NVPQOL, VAS, SDS and SAS), pregnancy complication, treatment
      compliance, neonatal outcomes; area under the curve of PUQE score, effect of intervention on
      PUQE score reduction over treatment period and adverse events.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: Two by two factorial design
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15
time frame: Baseline to day 15; Scores ranged 3 to 15, with higher scores indicating more
description: Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15
measure: Score change of maternal weight from baseline to the last visit
time frame: Baseline to day 15; no range of variation
description: Score change of maternal weight from baseline to the last visit
measure: Change of electrolyte index (sodium)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mmol/L
measure: Change of electrolyte index (potassium)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mmol/L
measure: Change of electrolyte index (calcium)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mmol/L
measure: Change of electrolyte index (chlorine)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mmol/L
measure: Change of electrolyte index (phosphorus)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mmol/L
measure: Change of electrolyte index (magnesium)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mmol/L
measure: Change of electrolyte index (iron)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: μmol/L
measure: Change of electrolyte index (zinc)
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: μmol/L
measure: Change of AST
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: U/L
measure: Change of ALT
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: U/L
measure: Change of ALP
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: U/L
measure: Change of creatinine
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: μmol/L
measure: Change of urea
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mmol/L
measure: Change of TSH
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: mIU/L
measure: Change of free triiodothyronine
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: pmol/L
measure: Change of free thyroxine
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: pmol/L
measure: Change of vitamin b1
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ng/ml
measure: Change of vitamin b6
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ng/ml
measure: Change of vitamin b12
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ng/ml
measure: Change of cortisol
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ug/dL
measure: Change of ghrelin
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ng/ml
measure: Change of leptin
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ng/ml
measure: Change of 5-hydroxytryptamine
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ng/ml
measure: Change of substance P
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: pg/ml
measure: Change of arginine vasopressin plasma
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: pg/ml
measure: Change of GDF 15
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: pg/ml
measure: Change of IGFBP 7
time frame: Baseline to day 15
description: Value changes from baseline to last Visit. Unit: ng/ml
measure: Intravenous fluid treatment during treatment
time frame: Baseline to day 15
description: Intravenous fluid treatment during treatment
measure: Concomitant treatment
time frame: Baseline to day 15
description: Concomitant treatment
measure: Hospital admission during treatment
time frame: Baseline to day 15
description: Hospital admission during treatment
measure: Termination of pregnancy
time frame: Data collected from baseline to the end of follow-up period (four weeks after the end of treatment).
description: Termination of pregnancy. If the patient is suffering further aggravation of hyperemesis gravidarum, the termination of a wanted pregnancy will be done due to life in danger. Or congenital anomalies are found by ultrasound, the termination of a wanted pregnancy will be done.
measure: Maternal outcomes
time frame: Data collected from baseline to 42 days after postpartum.
description: Including pregnancy complications, termination of pregnancy and birth outcomes. Pregnancy complications including miscarriage (in the first trimester and in the second trimester), hypertensive disorders, and gestational diabetes; birth outcomes including live birth, vaginal delivery, cesarean section, gestational age, preterm, birth weight and small for gestational age.
measure: Patient satisfaction with treatment
time frame: Baseline to day 15
description: Such as loss of confidence or intolerance to daily acupuncture and so on
measure: Treatment compliance
time frame: Baseline to day 15
description: Such as the percentage of drug or needle used; or drug tablets or acupuncture sessions.
measure: Offspring outcomes
time frame: Data collected from baseline to to 42 days after postpartum.
description: Including fetal and neonatal congenital anomalies, fetal and neonatal mortality, neonatal hypoglycemia and NICU admission.
measure: Area under the curve (AUC) of PUQE score over treatment
time frame: Baseline to day 15
description: Scores ranged 3 to 15, with higher scores indicating more severe NVP
measure: PUQE score reduction based on different TCM patterns
time frame: Scores ranged 3 to 15, with higher reduction indicating the better
description: PUQE score reduction based on different TCM patterns
measure: Adverse events and serious adverse events
time frame: Baseline to the end of follow-up (four weeks after the end of treatment)
description: The percentage of adverse events and serious adverse events
measure: Quality of life: NVPQoL
time frame: Baseline to day 15
description: Range 30-210, high being poor QoL
measure: Quality of life: VAS
time frame: Baseline to day 15
description: Ranged 0-10, high being more severe symptoms
measure: Quality of life: SDS
time frame: Baseline to day 15
description: Range 25-10, high being more severe
measure: Quality of life: SAS
time frame: Baseline to day 15
description: Range 25-100, high being more severe
measure: Quality of life: global assessment of well-being
time frame: Baseline to day 15
description: Range 0-10, low being more severe
measure: PUQE score reduction at different levels of NVP
time frame: Scores ranged 3 to 15, with higher reduction indicating the better
description: PUQE score reduction at different levels of NVP
arm group label: Diclectin plus active acupuncture
arm group type: Other
description: Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day) + active acupuncture (30 min /every day).
arm group label: Diclectin plus sham acupuncture
arm group type: Other
description: Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), 2-4 tablets/day) + sham acupuncture (30 min /every day).
arm group label: Placebo plus active acupuncture
arm group type: Other
description: Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day)
arm group label: Placebo plus sham acupuncture
arm group type: Other
description: Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day)
intervention type: Drug
intervention name: Diclectin
description: Diclectin (combination of 10 mg doxylamine and 10 mg pyridoxine hydrochloride in a delayed release tablet) During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of Diclectin or placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.
arm group label: Diclectin plus active acupuncture
arm group label: Diclectin plus sham acupuncture
intervention type: Drug
intervention name: Diclectin placebo
description: Diclectin placebo will be packed and tested by a commercial pharmacy supply company specifically for this study. It have the same appearance, size, batch, odor, and taste compared with Diclectin. During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.
arm group label: Placebo plus active acupuncture
arm group label: Placebo plus sham acupuncture
intervention type: Device
intervention name: Active acupuncture
description: Participants will receive active acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).
arm group label: Diclectin plus active acupuncture
arm group label: Placebo plus active acupuncture
intervention type: Device
intervention name: Sham acupuncture
description: Blunt-tipped placebo needles will be used. Participants will receive sham acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6). Then, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).
arm group label: Diclectin plus sham acupuncture
arm group label: Placebo plus sham acupuncture
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: No
last name: Xiaoke Wu, Ph.D
role: Study Chair
affiliation: First Affiliated Hospital of Heilongjiang University of Chinese Medicine
facility: 
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country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Heilongjiang University of Chinese Medicine
investigator full name: Xiaoke Wu
investigator title: Director of obstetrics and Gynecology Department
mesh term: Nausea
mesh term: Vomiting
mesh term: Pyridoxine
mesh term: Dicyclomine, doxylamine, pyridoxine drug combination
mesh term: Doxylamine
mesh term: Dicyclomine
sharing ipd: No