- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04401384
Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy
March 31, 2022 updated by: Xiaoke Wu
Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy: A Randomized Controlled Two-by-two Factorial Trial
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
352
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Heilongjiang
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Harbin, Heilongjiang, China
- Heilongjiang Provincial Hospital
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Harbin, Heilongjiang, China
- First Affiliated Hospital of Heilongjiang Chinese Medicine University
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Hegang, Heilongjiang, China
- Hegang Maternal and Child Health Hospital
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Jiamusi, Heilongjiang, China
- Affiliated Hospital of Jiamusi Medical University
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Jiamusi, Heilongjiang, China
- Jiamusi Maternal and Child Health Hospital
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Jixi, Heilongjiang, China
- Jixi Maternal and Child Health Hospital
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Mudanjiang, Heilongjiang, China
- Mudanjaing Maternal and Child Health Hospital
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Shuangyashan, Heilongjiang, China
- Shuangyashan Maternal and Child Health Hospital
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Heilongjing
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Suihua, Heilongjing, China
- Suihua Maternal and Child Health Hospital
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Henan
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Luoyang, Henan, China
- Luoyang Hospital of TCM
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Jiangsu
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Xuzhou, Jiangsu, China
- Xuzhou Central Hospital
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Jiangxi
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Nanchang, Jiangxi, China
- Jiangxi Maternal and Child Health Hospital
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Ningxia Hui Autonomous Region
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Yinchuan, Ningxia Hui Autonomous Region, China
- Ningxia Hui Autonomous Region Hospital of TCM
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 43 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: 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).
|
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.
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).
|
Other: 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).
|
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.
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).
|
Other: Placebo plus active acupuncture
Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day)
|
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).
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.
|
Other: Placebo plus sham acupuncture
Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day)
|
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).
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15
Time Frame: Baseline to day 15; Scores ranged 3 to 15, with higher scores indicating more
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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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Score change of maternal weight from baseline to the last visit
Time Frame: Baseline to day 15; no range of variation
|
Score change of maternal weight from baseline to the last visit
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Baseline to day 15; no range of variation
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Change of electrolyte index (sodium)
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: mmol/L
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Baseline to day 15
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Change of electrolyte index (potassium)
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: mmol/L
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Baseline to day 15
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Change of electrolyte index (calcium)
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: mmol/L
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Baseline to day 15
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Change of electrolyte index (chlorine)
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: mmol/L
|
Baseline to day 15
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Change of electrolyte index (phosphorus)
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: mmol/L
|
Baseline to day 15
|
Change of electrolyte index (magnesium)
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: mmol/L
|
Baseline to day 15
|
Change of electrolyte index (iron)
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: μmol/L
|
Baseline to day 15
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Change of electrolyte index (zinc)
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: μmol/L
|
Baseline to day 15
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Change of AST
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: U/L
|
Baseline to day 15
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Change of ALT
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: U/L
|
Baseline to day 15
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Change of ALP
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: U/L
|
Baseline to day 15
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Change of creatinine
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: μmol/L
|
Baseline to day 15
|
Change of urea
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: mmol/L
|
Baseline to day 15
|
Change of TSH
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: mIU/L
|
Baseline to day 15
|
Change of free triiodothyronine
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: pmol/L
|
Baseline to day 15
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Change of free thyroxine
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: pmol/L
|
Baseline to day 15
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Change of vitamin b1
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: ng/ml
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Baseline to day 15
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Change of vitamin b6
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: ng/ml
|
Baseline to day 15
|
Change of vitamin b12
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: ng/ml
|
Baseline to day 15
|
Change of cortisol
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: ug/dL
|
Baseline to day 15
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Change of ghrelin
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: ng/ml
|
Baseline to day 15
|
Change of leptin
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: ng/ml
|
Baseline to day 15
|
Change of 5-hydroxytryptamine
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: ng/ml
|
Baseline to day 15
|
Change of substance P
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: pg/ml
|
Baseline to day 15
|
Change of arginine vasopressin plasma
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: pg/ml
|
Baseline to day 15
|
Change of GDF 15
Time Frame: Baseline to day 15
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Value changes from baseline to last Visit.
Unit: pg/ml
|
Baseline to day 15
|
Change of IGFBP 7
Time Frame: Baseline to day 15
|
Value changes from baseline to last Visit.
Unit: ng/ml
|
Baseline to day 15
|
Intravenous fluid treatment during treatment
Time Frame: Baseline to day 15
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Intravenous fluid treatment during treatment
|
Baseline to day 15
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Concomitant treatment
Time Frame: Baseline to day 15
|
Concomitant treatment
|
Baseline to day 15
|
Hospital admission during treatment
Time Frame: Baseline to day 15
|
Hospital admission during treatment
|
Baseline to day 15
|
Termination of pregnancy
Time Frame: Data collected from baseline to the end of follow-up period (four weeks after the end of treatment).
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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).
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Maternal outcomes
Time Frame: Data collected from baseline to 42 days after postpartum.
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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.
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Data collected from baseline to 42 days after postpartum.
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Patient satisfaction with treatment
Time Frame: Baseline to day 15
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Such as loss of confidence or intolerance to daily acupuncture and so on
|
Baseline to day 15
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Treatment compliance
Time Frame: Baseline to day 15
|
Such as the percentage of drug or needle used; or drug tablets or acupuncture sessions.
|
Baseline to day 15
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Offspring outcomes
Time Frame: 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.
|
Data collected from baseline to to 42 days after postpartum.
|
Area under the curve (AUC) of PUQE score over treatment
Time Frame: Baseline to day 15
|
Scores ranged 3 to 15, with higher scores indicating more severe NVP
|
Baseline to day 15
|
PUQE score reduction based on different TCM patterns
Time Frame: Scores ranged 3 to 15, with higher reduction indicating the better
|
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
Time Frame: Baseline to the end of follow-up (four weeks after the end of treatment)
|
The percentage of adverse events and serious adverse events
|
Baseline to the end of follow-up (four weeks after the end of treatment)
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Quality of life: NVPQoL
Time Frame: Baseline to day 15
|
Range 30-210, high being poor QoL
|
Baseline to day 15
|
Quality of life: VAS
Time Frame: Baseline to day 15
|
Ranged 0-10, high being more severe symptoms
|
Baseline to day 15
|
Quality of life: SDS
Time Frame: Baseline to day 15
|
Range 25-10, high being more severe
|
Baseline to day 15
|
Quality of life: SAS
Time Frame: Baseline to day 15
|
Range 25-100, high being more severe
|
Baseline to day 15
|
Quality of life: global assessment of well-being
Time Frame: Baseline to day 15
|
Range 0-10, low being more severe
|
Baseline to day 15
|
PUQE score reduction at different levels of NVP
Time Frame: Scores ranged 3 to 15, with higher reduction indicating the better
|
PUQE score reduction at different levels of NVP
|
Scores ranged 3 to 15, with higher reduction indicating the better
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Xiaoke Wu, Ph.D, First Affiliated Hospital of Heilongjiang University of Chinese Medicine
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 21, 2020
Primary Completion (Actual)
June 23, 2021
Study Completion (Actual)
January 31, 2022
Study Registration Dates
First Submitted
May 18, 2020
First Submitted That Met QC Criteria
May 20, 2020
First Posted (Actual)
May 26, 2020
Study Record Updates
Last Update Posted (Actual)
April 4, 2022
Last Update Submitted That Met QC Criteria
March 31, 2022
Last Verified
March 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Signs and Symptoms, Digestive
- Nausea
- Vomiting
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Antiemetics
- Gastrointestinal Agents
- Micronutrients
- Vitamins
- Vitamin B Complex
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Pyridoxine
- Doxylamine
- Dicyclomine, doxylamine, pyridoxine drug combination
- Dicyclomine
Other Study ID Numbers
- NVPAct
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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