Clinical trial NCT04401384: Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nausea and Vomiting of Pregnancy
Keywords: Nausea and Vomiting of Pregnancy
PUQE
Acupuncture
Diclectin
Lead sponsor: Heilongjiang University of Chinese Medicine
Sponsor class: OTHER
Collaborators: name: Ningxia Hui Autonomous Region Hospital of TCM
name: Jiangxi Maternal and Child Health Hospital
name: Jixi Maternal and Child Health Hospital
name: Luoyang Hospital of TCM
name: Xuzhou Central Hospital
name: First Affiliated Hospital of Heilongjiang Chinese Medicine University
name: Shuangyashan Maternal and Child Health Hospital
name: Heilongjiang provincial hospital
name: Jiamusi Maternal and Child Health Hospital
name: Hegang Maternal and Child Health Hospital
name: Suihua Maternal and Child Health Hospital
name: Mudanjaing Maternal and Child Health Hospital
name: Affiliated Hospital of Jiamusi Medical University
First posted: 2020-05-26
Enrollment: 352
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Two by two factorial design
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Women with 20-45 years of age;
2. PUQE score ≥6;
3. 7-14 weeks of gestation with viable fetus inside the uterine cavity confirmed by ultrasound dating;
4. Less than 20% weight loss.

Exclusion Criteria:

1. Having major medical problems such as malignant tumor, acute or subacute severe hepatitis, severe aplastic anemia, idiopathic thrombocytopenic purpura, acute appendicitis, acute pancreatitis, TORCH syndrome, etc
2. Having chronic medical conditions such as poorly controlled diabetes, coronary heart disease, uncontrolled hypertension, etc
3. Coexistence of other diseases that cause vomiting such as infectious disease, gestational trophoblastic disease, etc
4. Having asthma, increased intraocular pressure, narrow-angle glaucoma, narrow peptic ulcer, pyloric obstruction, bladder neck obstruction, etc
5. Taking antiemetics such as vitamin B6, ondansetron, metoclopramide, prednisone, anti-vomiting Chinese medicine, etc., within the past week
6. Receiving conservative treatment such as dietary and lifestyle modification
7. Abnormal physical examination and laboratory tests (minor abnormalities in laboratory tests due to pregnancy vomiting, such as liver function and ions, are acceptable for inclusion)
8. Having mental handicaps or psychological disorders
9. Allergic to doxylamine, other ethanolamine-derived antihistamines, pyridoxine hydrochloride, or any inactive ingredient in diclectin
10. Using monoamine oxidase inhibitors
11. Driving or operating heavy machinery
12. Using alcohol or other central nervous system inhibitors

Primary outcomes:
measure: Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15
timeFrame: Baseline to day 15; Scores ranged 3 to 15, with higher scores indicating more
Secondary outcomes:
measure: Score change of maternal weight from baseline to the last visit
timeFrame: Baseline to day 15; no range of variation
measure: Change of electrolyte index (sodium)
timeFrame: Baseline to day 15
measure: Change of electrolyte index (potassium)
timeFrame: Baseline to day 15
measure: Change of electrolyte index (calcium)
timeFrame: Baseline to day 15
measure: Change of electrolyte index (chlorine)
timeFrame: Baseline to day 15
measure: Change of electrolyte index (phosphorus)
timeFrame: Baseline to day 15
measure: Change of electrolyte index (magnesium)
timeFrame: Baseline to day 15
measure: Change of electrolyte index (iron)
timeFrame: Baseline to day 15
measure: Change of electrolyte index (zinc)
timeFrame: Baseline to day 15
measure: Change of AST
timeFrame: Baseline to day 15
measure: Change of ALT
timeFrame: Baseline to day 15
measure: Change of ALP
timeFrame: Baseline to day 15
measure: Change of creatinine
timeFrame: Baseline to day 15
measure: Change of urea
timeFrame: Baseline to day 15
measure: Change of TSH
timeFrame: Baseline to day 15
measure: Change of free triiodothyronine
timeFrame: Baseline to day 15
measure: Change of free thyroxine
timeFrame: Baseline to day 15
measure: Change of vitamin b1
timeFrame: Baseline to day 15
measure: Change of vitamin b6
timeFrame: Baseline to day 15
measure: Change of vitamin b12
timeFrame: Baseline to day 15
measure: Change of cortisol
timeFrame: Baseline to day 15
measure: Change of ghrelin
timeFrame: Baseline to day 15
measure: Change of leptin
timeFrame: Baseline to day 15
measure: Change of 5-hydroxytryptamine
timeFrame: Baseline to day 15
measure: Change of substance P
timeFrame: Baseline to day 15
measure: Change of arginine vasopressin plasma
timeFrame: Baseline to day 15
measure: Change of GDF 15
timeFrame: Baseline to day 15
measure: Change of IGFBP 7
timeFrame: Baseline to day 15
measure: Intravenous fluid treatment during treatment
timeFrame: Baseline to day 15
measure: Concomitant treatment
timeFrame: Baseline to day 15
measure: Hospital admission during treatment
timeFrame: Baseline to day 15
measure: Termination of pregnancy
timeFrame: Data collected from baseline to the end of follow-up period (four weeks after the end of treatment).
measure: Maternal outcomes
timeFrame: Data collected from baseline to 42 days after postpartum.
measure: Patient satisfaction with treatment
timeFrame: Baseline to day 15
measure: Treatment compliance
timeFrame: Baseline to day 15
measure: Offspring outcomes
timeFrame: Data collected from baseline to to 42 days after postpartum.
measure: Area under the curve (AUC) of PUQE score over treatment
timeFrame: Baseline to day 15
measure: PUQE score reduction based on different TCM patterns
timeFrame: Scores ranged 3 to 15, with higher reduction indicating the better
measure: Adverse events and serious adverse events
timeFrame: Baseline to the end of follow-up (four weeks after the end of treatment)
measure: Quality of life: NVPQoL
timeFrame: Baseline to day 15
measure: Quality of life: VAS
timeFrame: Baseline to day 15
measure: Quality of life: SDS
timeFrame: Baseline to day 15
measure: Quality of life: SAS
timeFrame: Baseline to day 15
measure: Quality of life: global assessment of well-being
timeFrame: Baseline to day 15
measure: PUQE score reduction at different levels of NVP
timeFrame: Scores ranged 3 to 15, with higher reduction indicating the better
Other outcomes:
Locations:
city: Harbin
country: China
facility: First Affiliated Hospital of Heilongjiang Chinese Medicine University
state: Heilongjiang
city: Harbin
country: China
facility: Heilongjiang provincial hospital
state: Heilongjiang
city: Hegang
country: China
facility: Hegang Maternal and Child Health Hospital
state: Heilongjiang
city: Jiamusi
country: China
facility: Affiliated Hospital of Jiamusi Medical University
state: Heilongjiang
city: Jiamusi
country: China
facility: Jiamusi Maternal and Child Health Hospital
state: Heilongjiang
city: Jixi
country: China
facility: Jixi Maternal and Child Health Hospital
state: Heilongjiang
city: Mudanjiang
country: China
facility: Mudanjaing Maternal and Child Health Hospital
state: Heilongjiang
city: Shuangyashan
country: China
facility: Shuangyashan Maternal and Child Health Hospital
state: Heilongjiang
city: Suihua
country: China
facility: Suihua Maternal and Child Health Hospital
state: Heilongjing
city: Luoyang
country: China
facility: Luoyang Hospital of TCM
state: Henan
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Maternal and Child Health Hospital
state: Jiangxi
city: Yinchuan
country: China
facility: Ningxia Hui Autonomous Region Hospital of TCM
state: Ningxia Hui Autonomous Region
Study officials:
affiliation: First Affiliated Hospital of Heilongjiang University of Chinese Medicine
name: Xiaoke Wu, Ph.D
role: STUDY_CHAIR
References: