Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy
Condition: Nausea and Vomiting of Pregnancy
MeSH terms: Nausea; Vomiting
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Diclectin; Diclectin placebo; Active acupuncture; Sham acupuncture
Intervention type(s): Drug; Drug; Device; Device
Intervention description(s): 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.; 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.; 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).; 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).
Intervention MeSH terms: Pyridoxine; Dicyclomine, doxylamine, pyridoxine drug combination; Doxylamine; Dicyclomine
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Two by two factorial design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Nausea and Vomiting of Pregnancy; PUQE; Acupuncture; Diclectin