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| Name | Class |
|---|---|
| Ningxia Hui Autonomous Region Hospital of TCM | UNKNOWN |
| Jiangxi Maternal and Child Health Hospital | OTHER |
| Jixi Maternal and Child Health Hospital | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diclectin plus active acupuncture | Other | 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 | Other | 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 | Other | Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day) |
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| Placebo plus sham acupuncture | Other | Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Diclectin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Score change of maternal weight from baseline to the last visit | Score change of maternal weight from baseline to the last visit | Baseline to day 15; no range of variation |
| Change of electrolyte index (sodium) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiaoke Wu, Ph.D | First Affiliated Hospital of Heilongjiang University of Chinese Medicine | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| First Affiliated Hospital of Heilongjiang Chinese Medicine University | Harbin | Heilongjiang | China | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37335994 | Derived | Wu XK, Gao JS, Ma HL, Wang Y, Zhang B, Liu ZL, Li J, Cong J, Qin HC, Yang XM, Wu Q, Chen XY, Lu ZL, Feng YH, Qi X, Wang YX, Yu L, Cui YM, An CM, Zhou LL, Hu YH, Li L, Cao YJ, Yan Y, Liu L, Liu YX, Liu ZS, Painter RC, Ng EHY, Liu JP, Mol BWJ, Wang CC. Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 x 2 Factorial Trial. Ann Intern Med. 2023 Jul;176(7):922-933. doi: 10.7326/M22-2974. Epub 2023 Jun 20. |
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| Luoyang Hospital of TCM |
| UNKNOWN |
| Xuzhou Central Hospital | OTHER |
| First Affiliated Hospital of Heilongjiang Chinese Medicine University | OTHER |
| Shuangyashan Maternal and Child Health Hospital | UNKNOWN |
| Heilongjiang Provicial Hospital | OTHER |
| Jiamusi Maternal and Child Health Hospital | UNKNOWN |
| Hegang Maternal and Child Health Hospital | UNKNOWN |
| Suihua Maternal and Child Health Hospital | UNKNOWN |
| Mudanjaing Maternal and Child Health Hospital | UNKNOWN |
| Affiliated Hospital of Jiamusi Medical University | UNKNOWN |
Two by two factorial design
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| Diclectin placebo | Drug | 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. |
|
| Active acupuncture | Device | 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). |
|
| Sham acupuncture | Device | 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). |
|
Value changes from baseline to last Visit. Unit: mmol/L
| Baseline to day 15 |
| Change of electrolyte index (potassium) | Value changes from baseline to last Visit. Unit: mmol/L | Baseline to day 15 |
| Change of electrolyte index (calcium) | Value changes from baseline to last Visit. Unit: mmol/L | Baseline to day 15 |
| Change of electrolyte index (chlorine) | Value changes from baseline to last Visit. Unit: mmol/L | Baseline to day 15 |
| Change of electrolyte index (phosphorus) | Value changes from baseline to last Visit. Unit: mmol/L | Baseline to day 15 |
| Change of electrolyte index (magnesium) | Value changes from baseline to last Visit. Unit: mmol/L | Baseline to day 15 |
| Change of electrolyte index (iron) | Value changes from baseline to last Visit. Unit: μmol/L | Baseline to day 15 |
| Change of electrolyte index (zinc) | Value changes from baseline to last Visit. Unit: μmol/L | Baseline to day 15 |
| Change of AST | Value changes from baseline to last Visit. Unit: U/L | Baseline to day 15 |
| Change of ALT | Value changes from baseline to last Visit. Unit: U/L | Baseline to day 15 |
| Change of ALP | Value changes from baseline to last Visit. Unit: U/L | Baseline to day 15 |
| Change of creatinine | Value changes from baseline to last Visit. Unit: μmol/L | Baseline to day 15 |
| Change of urea | Value changes from baseline to last Visit. Unit: mmol/L | Baseline to day 15 |
| Change of TSH | Value changes from baseline to last Visit. Unit: mIU/L | Baseline to day 15 |
| Change of free triiodothyronine | Value changes from baseline to last Visit. Unit: pmol/L | Baseline to day 15 |
| Change of free thyroxine | Value changes from baseline to last Visit. Unit: pmol/L | Baseline to day 15 |
| Change of vitamin b1 | Value changes from baseline to last Visit. Unit: ng/ml | Baseline to day 15 |
| Change of vitamin b6 | Value changes from baseline to last Visit. Unit: ng/ml | Baseline to day 15 |
| Change of vitamin b12 | Value changes from baseline to last Visit. Unit: ng/ml | Baseline to day 15 |
| Change of cortisol | Value changes from baseline to last Visit. Unit: ug/dL | Baseline to day 15 |
| Change of ghrelin | Value changes from baseline to last Visit. Unit: ng/ml | Baseline to day 15 |
| Change of leptin | Value changes from baseline to last Visit. Unit: ng/ml | Baseline to day 15 |
| Change of 5-hydroxytryptamine | Value changes from baseline to last Visit. Unit: ng/ml | Baseline to day 15 |
| Change of substance P | Value changes from baseline to last Visit. Unit: pg/ml | Baseline to day 15 |
| Change of arginine vasopressin plasma | Value changes from baseline to last Visit. Unit: pg/ml | Baseline to day 15 |
| Change of GDF 15 | Value changes from baseline to last Visit. Unit: pg/ml | Baseline to day 15 |
| Change of IGFBP 7 | Value changes from baseline to last Visit. Unit: ng/ml | Baseline to day 15 |
| Intravenous fluid treatment during treatment | Intravenous fluid treatment during treatment | Baseline to day 15 |
| Concomitant treatment | Concomitant treatment | Baseline to day 15 |
| Hospital admission during treatment | Hospital admission during treatment | Baseline to day 15 |
| Termination of pregnancy | 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. | Data collected from baseline to the end of follow-up period (four weeks after the end of treatment). |
| Maternal outcomes | 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. | Data collected from baseline to 42 days after postpartum. |
| Patient satisfaction with treatment | Such as loss of confidence or intolerance to daily acupuncture and so on | Baseline to day 15 |
| Treatment compliance | Such as the percentage of drug or needle used; or drug tablets or acupuncture sessions. | Baseline to day 15 |
| Offspring outcomes | Including fetal and neonatal congenital anomalies, fetal and neonatal mortality, neonatal hypoglycemia and NICU admission. | Data collected from baseline to to 42 days after postpartum. |
| Area under the curve (AUC) of PUQE score over treatment | Scores ranged 3 to 15, with higher scores indicating more severe NVP | Baseline to day 15 |
| PUQE score reduction based on different TCM patterns | 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 | The percentage of adverse events and serious adverse events | Baseline to the end of follow-up (four weeks after the end of treatment) |
| Quality of life: NVPQoL | Range 30-210, high being poor QoL | Baseline to day 15 |
| Quality of life: VAS | Ranged 0-10, high being more severe symptoms | Baseline to day 15 |
| Quality of life: SDS | Range 25-10, high being more severe | Baseline to day 15 |
| Quality of life: SAS | Range 25-100, high being more severe | Baseline to day 15 |
| Quality of life: global assessment of well-being | Range 0-10, low being more severe | Baseline to day 15 |
| PUQE score reduction at different levels of NVP | PUQE score reduction at different levels of NVP | Scores ranged 3 to 15, with higher reduction indicating the better |
| Heilongjiang provincial hospital |
| Harbin |
| Heilongjiang |
| China |
| Hegang Maternal and Child Health Hospital | Hegang | Heilongjiang | China |
| Affiliated Hospital of Jiamusi Medical University | Jiamusi | Heilongjiang | China |
| Jiamusi Maternal and Child Health Hospital | Jiamusi | Heilongjiang | China |
| Jixi Maternal and Child Health Hospital | Jixi | Heilongjiang | China |
| Mudanjaing Maternal and Child Health Hospital | Mudanjiang | Heilongjiang | China |
| Shuangyashan Maternal and Child Health Hospital | Shuangyashan | Heilongjiang | China |
| Suihua Maternal and Child Health Hospital | Suihua | Heilongjing | China |
| Luoyang Hospital of TCM | Luoyang | Henan | China |
| Xuzhou Central Hospital | Xuzhou | Jiangsu | China |
| Jiangxi Maternal and Child Health Hospital | Nanchang | Jiangxi | China |
| Ningxia Hui Autonomous Region Hospital of TCM | Yinchuan | Ningxia | China |
| ID | Term |
|---|---|
| D009325 | Nausea |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C004454 | dicyclomine, doxylamine, pyridoxine drug combination |
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