Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy
- Conditions
- Nausea and Vomiting of Pregnancy
- Interventions
- Registration Number
- NCT04401384
- Lead Sponsor
- Xiaoke Wu
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 352
- Women with 20-45 years of age;
- PUQE score ≥6;
- 7-14 weeks of gestation with viable fetus inside the uterine cavity confirmed by ultrasound dating;
- Less than 20% weight loss.
- 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
- Having chronic medical conditions such as poorly controlled diabetes, coronary heart disease, uncontrolled hypertension, etc
- Coexistence of other diseases that cause vomiting such as infectious disease, gestational trophoblastic disease, etc
- Having asthma, increased intraocular pressure, narrow-angle glaucoma, narrow peptic ulcer, pyloric obstruction, bladder neck obstruction, etc
- Taking antiemetics such as vitamin B6, ondansetron, metoclopramide, prednisone, anti-vomiting Chinese medicine, etc., within the past week
- Receiving conservative treatment such as dietary and lifestyle modification
- 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)
- Having mental handicaps or psychological disorders
- Allergic to doxylamine, other ethanolamine-derived antihistamines, pyridoxine hydrochloride, or any inactive ingredient in diclectin
- Using monoamine oxidase inhibitors
- Driving or operating heavy machinery
- Using alcohol or other central nervous system inhibitors
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Diclectin plus active acupuncture Active acupuncture Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day) + active acupuncture (30 min /every day). Diclectin plus sham acupuncture Sham acupuncture Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), 2-4 tablets/day) + sham acupuncture (30 min /every day). Placebo plus active acupuncture Active acupuncture Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day) Placebo plus sham acupuncture Sham acupuncture Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day) Placebo plus active acupuncture Diclectin placebo Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day) Placebo plus sham acupuncture Diclectin placebo Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day) Diclectin plus active acupuncture Diclectin Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day) + active acupuncture (30 min /every day). Diclectin plus sham acupuncture Diclectin Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), 2-4 tablets/day) + sham acupuncture (30 min /every day).
- Primary Outcome Measures
Name Time Method Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15 Baseline to day 15; Scores ranged 3 to 15, with higher scores indicating more Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15
- Secondary Outcome Measures
Name Time Method Change of electrolyte index (potassium) Baseline to day 15 Value changes from baseline to last Visit. Unit: mmol/L
Change of electrolyte index (calcium) Baseline to day 15 Value changes from baseline to last Visit. Unit: mmol/L
Change of electrolyte index (zinc) Baseline to day 15 Value changes from baseline to last Visit. Unit: μmol/L
Change of AST Baseline to day 15 Value changes from baseline to last Visit. Unit: U/L
Change of ALT Baseline to day 15 Value changes from baseline to last Visit. Unit: U/L
Change of ALP Baseline to day 15 Value changes from baseline to last Visit. Unit: U/L
Change of creatinine Baseline to day 15 Value changes from baseline to last Visit. Unit: μmol/L
Change of urea Baseline to day 15 Value changes from baseline to last Visit. Unit: mmol/L
Score change of maternal weight from baseline to the last visit Baseline to day 15; no range of variation Score change of maternal weight from baseline to the last visit
Change of electrolyte index (sodium) Baseline to day 15 Value changes from baseline to last Visit. Unit: mmol/L
Change of electrolyte index (chlorine) Baseline to day 15 Value changes from baseline to last Visit. Unit: mmol/L
Change of electrolyte index (phosphorus) Baseline to day 15 Value changes from baseline to last Visit. Unit: mmol/L
Change of electrolyte index (magnesium) Baseline to day 15 Value changes from baseline to last Visit. Unit: mmol/L
Change of electrolyte index (iron) Baseline to day 15 Value changes from baseline to last Visit. Unit: μmol/L
Change of TSH Baseline to day 15 Value changes from baseline to last Visit. Unit: mIU/L
Change of free triiodothyronine Baseline to day 15 Value changes from baseline to last Visit. Unit: pmol/L
Change of free thyroxine Baseline to day 15 Value changes from baseline to last Visit. Unit: pmol/L
Change of vitamin b1 Baseline to day 15 Value changes from baseline to last Visit. Unit: ng/ml
Change of vitamin b6 Baseline to day 15 Value changes from baseline to last Visit. Unit: ng/ml
Change of vitamin b12 Baseline to day 15 Value changes from baseline to last Visit. Unit: ng/ml
Change of cortisol Baseline to day 15 Value changes from baseline to last Visit. Unit: ug/dL
Change of ghrelin Baseline to day 15 Value changes from baseline to last Visit. Unit: ng/ml
Change of leptin Baseline to day 15 Value changes from baseline to last Visit. Unit: ng/ml
Change of 5-hydroxytryptamine Baseline to day 15 Value changes from baseline to last Visit. Unit: ng/ml
Concomitant treatment Baseline to day 15 Concomitant treatment
Change of substance P Baseline to day 15 Value changes from baseline to last Visit. Unit: pg/ml
Change of arginine vasopressin plasma Baseline to day 15 Value changes from baseline to last Visit. Unit: pg/ml
Change of GDF 15 Baseline to day 15 Value changes from baseline to last Visit. Unit: pg/ml
Change of IGFBP 7 Baseline to day 15 Value changes from baseline to last Visit. Unit: ng/ml
Intravenous fluid treatment during treatment Baseline to day 15 Intravenous fluid treatment during treatment
Termination of pregnancy Data collected from baseline to the end of follow-up period (four weeks after the end of treatment). 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.
Maternal outcomes Data collected from baseline to 42 days after postpartum. 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.
Patient satisfaction with treatment Baseline to day 15 Such as loss of confidence or intolerance to daily acupuncture and so on
Offspring outcomes Data collected from baseline to to 42 days after postpartum. Including fetal and neonatal congenital anomalies, fetal and neonatal mortality, neonatal hypoglycemia and NICU admission.
Hospital admission during treatment Baseline to day 15 Hospital admission during treatment
Treatment compliance Baseline to day 15 Such as the percentage of drug or needle used; or drug tablets or acupuncture sessions.
Area under the curve (AUC) of PUQE score over treatment Baseline to day 15 Scores ranged 3 to 15, with higher scores indicating more severe NVP
PUQE score reduction based on different TCM patterns Scores ranged 3 to 15, with higher reduction indicating the better PUQE score reduction based on different TCM patterns
Adverse events and serious adverse events Baseline to the end of follow-up (four weeks after the end of treatment) The percentage of adverse events and serious adverse events
Quality of life: NVPQoL Baseline to day 15 Range 30-210, high being poor QoL
Quality of life: VAS Baseline to day 15 Ranged 0-10, high being more severe symptoms
Quality of life: SDS Baseline to day 15 Range 25-10, high being more severe
Quality of life: SAS Baseline to day 15 Range 25-100, high being more severe
Quality of life: global assessment of well-being Baseline to day 15 Range 0-10, low being more severe
PUQE score reduction at different levels of NVP Scores ranged 3 to 15, with higher reduction indicating the better PUQE score reduction at different levels of NVP
Trial Locations
- Locations (13)
Heilongjiang provincial hospital
🇨🇳Harbin, Heilongjiang, China
First Affiliated Hospital of Heilongjiang Chinese Medicine University
🇨🇳Harbin, Heilongjiang, China
Mudanjaing Maternal and Child Health Hospital
🇨🇳Mudanjiang, Heilongjiang, China
Hegang Maternal and Child Health Hospital
🇨🇳Hegang, Heilongjiang, China
Luoyang Hospital of TCM
🇨🇳Luoyang, Henan, China
Jiamusi Maternal and Child Health Hospital
🇨🇳Jiamusi, Heilongjiang, China
Suihua Maternal and Child Health Hospital
🇨🇳Suihua, Heilongjing, China
Ningxia Hui Autonomous Region Hospital of TCM
🇨🇳Yinchuan, Ningxia Hui Autonomous Region, China
Jixi Maternal and Child Health Hospital
🇨🇳Jixi, Heilongjiang, China
Xuzhou Central Hospital
🇨🇳Xuzhou, Jiangsu, China
Affiliated Hospital of Jiamusi Medical University
🇨🇳Jiamusi, Heilongjiang, China
Shuangyashan Maternal and Child Health Hospital
🇨🇳Shuangyashan, Heilongjiang, China
Jiangxi Maternal and Child Health Hospital
🇨🇳Nanchang, Jiangxi, China