Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy: A Randomized Controlled Two-by-two Factorial Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 352
- 试验地点
- 13
- 主要终点
- Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Diclectin plus active acupuncture
Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day) + active acupuncture (30 min /every day).
干预措施: Diclectin (Drug)
Diclectin plus active acupuncture
Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day) + active acupuncture (30 min /every day).
干预措施: Active acupuncture (Device)
Diclectin plus sham acupuncture
Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), 2-4 tablets/day) + sham acupuncture (30 min /every day).
干预措施: Diclectin (Drug)
Diclectin plus sham acupuncture
Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), 2-4 tablets/day) + sham acupuncture (30 min /every day).
干预措施: Sham acupuncture (Device)
Placebo plus active acupuncture
Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day)
干预措施: Diclectin placebo (Drug)
Placebo plus active acupuncture
Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day)
干预措施: Active acupuncture (Device)
Placebo plus sham acupuncture
Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day)
干预措施: Diclectin placebo (Drug)
Placebo plus sham acupuncture
Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day)
干预措施: Sham acupuncture (Device)
结局指标
主要结局
Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15
时间窗: 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
次要结局
- Change of urea(Baseline to day 15)
- Change of electrolyte index (potassium)(Baseline to day 15)
- Change of electrolyte index (calcium)(Baseline to day 15)
- Change of electrolyte index (zinc)(Baseline to day 15)
- Change of AST(Baseline to day 15)
- Change of ALT(Baseline to day 15)
- Change of ALP(Baseline to day 15)
- Change of creatinine(Baseline to day 15)
- Score change of maternal weight from baseline to the last visit(Baseline to day 15; no range of variation)
- Change of electrolyte index (sodium)(Baseline to day 15)
- Change of electrolyte index (chlorine)(Baseline to day 15)
- Change of electrolyte index (phosphorus)(Baseline to day 15)
- Change of electrolyte index (magnesium)(Baseline to day 15)
- Change of electrolyte index (iron)(Baseline to day 15)
- Change of TSH(Baseline to day 15)
- Change of free triiodothyronine(Baseline to day 15)
- Change of free thyroxine(Baseline to day 15)
- Change of vitamin b1(Baseline to day 15)
- Change of vitamin b6(Baseline to day 15)
- Change of vitamin b12(Baseline to day 15)
- Change of cortisol(Baseline to day 15)
- Change of ghrelin(Baseline to day 15)
- Change of leptin(Baseline to day 15)
- Change of 5-hydroxytryptamine(Baseline to day 15)
- Concomitant treatment(Baseline to day 15)
- Change of substance P(Baseline to day 15)
- Change of arginine vasopressin plasma(Baseline to day 15)
- Change of GDF 15(Baseline to day 15)
- Change of IGFBP 7(Baseline to day 15)
- Intravenous fluid treatment during treatment(Baseline to day 15)
- Termination of pregnancy(Data collected from baseline to the end of follow-up period (four weeks after the end of treatment).)
- Maternal outcomes(Data collected from baseline to 42 days after postpartum.)
- Patient satisfaction with treatment(Baseline to day 15)
- Offspring outcomes(Data collected from baseline to to 42 days after postpartum.)
- Hospital admission during treatment(Baseline to day 15)
- Treatment compliance(Baseline to day 15)
- Area under the curve (AUC) of PUQE score over treatment(Baseline to day 15)
- PUQE score reduction based on different TCM patterns(Scores ranged 3 to 15, with higher reduction indicating the better)
- Adverse events and serious adverse events(Baseline to the end of follow-up (four weeks after the end of treatment))
- Quality of life: NVPQoL(Baseline to day 15)
- Quality of life: VAS(Baseline to day 15)
- Quality of life: SDS(Baseline to day 15)
- Quality of life: SAS(Baseline to day 15)
- Quality of life: global assessment of well-being(Baseline to day 15)
- PUQE score reduction at different levels of NVP(Scores ranged 3 to 15, with higher reduction indicating the better)
研究者
Xiaoke Wu
Director of obstetrics and Gynecology Department
Heilongjiang University of Chinese Medicine