Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy

NCT ID: NCT04401384

Last Updated: 2022-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-21
• Study Completion Date: 2022-01-31

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.

Conditions

Nausea and Vomiting of Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: OTHER

Diclectin

Intervention Type: 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.

Active acupuncture

Intervention Type: 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).

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).

Group Type: OTHER

Diclectin

Intervention Type: 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.

Sham acupuncture

Intervention Type: 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).

Placebo plus active acupuncture

Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day)

Group Type: OTHER

Diclectin placebo

Intervention Type: 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

Intervention Type: 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).

Placebo plus sham acupuncture

Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day)

Group Type: OTHER

Diclectin placebo

Intervention Type: 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.

Sham acupuncture

Intervention Type: 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).

Interventions

Diclectin

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.

Intervention Type: DRUG

Diclectin placebo

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.

Intervention Type: DRUG

Active acupuncture

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).

Intervention Type: DEVICE

Sham acupuncture

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).

Intervention Type: DEVICE

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ningxia Hui Autonomous Region Hospital of TCM

UNKNOWN

Sponsor Role: collaborator

Jiangxi Maternal and Child Health Hospital

OTHER

Sponsor Role: collaborator

Jixi Maternal and Child Health Hospital

UNKNOWN

Sponsor Role: collaborator

Luoyang Hospital of TCM

UNKNOWN

Sponsor Role: collaborator

Xuzhou Central Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Heilongjiang Chinese Medicine University

OTHER

Sponsor Role: collaborator

Shuangyashan Maternal and Child Health Hospital

UNKNOWN

Sponsor Role: collaborator

Heilongjiang provincial hospital

UNKNOWN

Sponsor Role: collaborator

Jiamusi Maternal and Child Health Hospital

UNKNOWN

Sponsor Role: collaborator

Hegang Maternal and Child Health Hospital

UNKNOWN

Sponsor Role: collaborator

Suihua Maternal and Child Health Hospital

UNKNOWN

Sponsor Role: collaborator

Mudanjaing Maternal and Child Health Hospital

UNKNOWN

Sponsor Role: collaborator

Affiliated Hospital of Jiamusi Medical University

UNKNOWN

Sponsor Role: collaborator

Xiaoke Wu

OTHER

Sponsor Role: lead

Responsible Party

Xiaoke Wu

Director of obstetrics and Gynecology Department

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Xiaoke Wu, Ph.D

Role: STUDY_CHAIR

First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Locations

First Affiliated Hospital of Heilongjiang Chinese Medicine University

Harbin, Heilongjiang, China

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

Countries

China

References

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.

Reference Type: DERIVED

PMID: 37335994 (View on PubMed)

Other Identifiers

NVPAct

Identifier Type: -

Identifier Source: org_study_id