NCT04401384

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
352

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jun 2020

Geographic Reach
1 country

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 18, 2020

Completed
8 days until next milestone

First Posted

Study publicly available on registry

May 26, 2020

Completed
26 days until next milestone

Study Start

First participant enrolled

June 21, 2020

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 23, 2021

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2022

Completed
Last Updated

April 4, 2022

Status Verified

March 1, 2022

Enrollment Period

1 year

First QC Date

May 18, 2020

Last Update Submit

March 31, 2022

Conditions

Nausea and Vomiting of Pregnancy

Keywords

Nausea and Vomiting of PregnancyPUQEAcupunctureDiclectin

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (45)

  • 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 (potassium)

    Baseline to day 15

  • Change of electrolyte index (calcium)

    Baseline to day 15

  • Change of electrolyte index (chlorine)

    Baseline to day 15

  • +40 more secondary outcomes

Study Arms (4)

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).

Drug: DiclectinDevice: Active acupuncture

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).

Drug: DiclectinDevice: Sham acupuncture

Placebo plus active acupuncture

OTHER

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

Drug: Diclectin placeboDevice: Active acupuncture

Placebo plus sham acupuncture

OTHER

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

Drug: Diclectin placeboDevice: Sham acupuncture

Interventions

DiclectinDRUG

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.

Diclectin plus active acupunctureDiclectin plus sham acupuncture
Diclectin placeboDRUG

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.

Placebo plus active acupuncturePlacebo plus sham acupuncture
Active acupunctureDEVICE

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 active acupuncturePlacebo plus active acupuncture
Sham acupunctureDEVICE

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 plus sham acupuncturePlacebo plus sham acupuncture

Eligibility Criteria

Age20 Years - 45 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Women with 20-45 years of age;
  • PUQE score ≥6;
  • weeks of gestation with viable fetus inside the uterine cavity confirmed by ultrasound dating;
  • Less than 20% weight loss.

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

First Affiliated Hospital of Heilongjiang Chinese Medicine University

Harbin, Heilongjiang, China

Location

Heilongjiang provincial hospital

Harbin, Heilongjiang, China

Location

Hegang Maternal and Child Health Hospital

Hegang, Heilongjiang, China

Location

Affiliated Hospital of Jiamusi Medical University

Jiamusi, Heilongjiang, China

Location

Jiamusi Maternal and Child Health Hospital

Jiamusi, Heilongjiang, China

Location

Jixi Maternal and Child Health Hospital

Jixi, Heilongjiang, China

Location

Mudanjaing Maternal and Child Health Hospital

Mudanjiang, Heilongjiang, China

Location

Shuangyashan Maternal and Child Health Hospital

Shuangyashan, Heilongjiang, China

Location

Suihua Maternal and Child Health Hospital

Suihua, Heilongjing, China

Location

Luoyang Hospital of TCM

Luoyang, Henan, China

Location

Xuzhou Central Hospital

Xuzhou, Jiangsu, China

Location

Jiangxi Maternal and Child Health Hospital

Nanchang, Jiangxi, China

Location

Ningxia Hui Autonomous Region Hospital of TCM

Yinchuan, Ningxia, China

Location

Related Publications (1)

  • 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.

    PMID: 37335994DERIVED

MeSH Terms

Conditions

Nausea

Interventions

dicyclomine, doxylamine, pyridoxine drug combination

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Xiaoke Wu, Ph.D

    First Affiliated Hospital of Heilongjiang University of Chinese Medicine

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
FACTORIAL
Model Details: Two by two factorial design
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Director of obstetrics and Gynecology Department

Study Record Dates

First Submitted

May 18, 2020

First Posted

May 26, 2020

Study Start

June 21, 2020

Primary Completion

June 23, 2021

Study Completion

January 31, 2022

Last Updated

April 4, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will not share

Locations

CN(13)