Effect Comparison of Electro-acupuncture and Prucalopride for Severe Chronic Constipation: a Randomized Controlled Trial

• Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT02047045
• Collaborator: Ministry of Science and Technology of the People´s Republic of China (Other)
• Enrollment: 560
• Arms: 2
• Duration (Months): 37

Study Details

Study Description

Brief Summary

This trial is primarily aimed to compare the effect and safety of electro-acupuncture and prucalopride for severe chronic constipation: if the short-term effect of electro-acupuncture is no inferior to prucalopride? Besides, the investigators will also mainly confirm the superiority of electro-acupuncture: if the effect of electro-acupuncture can last for 3~6 months? Then, assess the patients' acceptance of electro-acupuncture.

Condition or Disease	Intervention/Treatment	Phase
Constipation	Procedure: acupuncture; Drug: Prucalopride	N/A

Detailed Description

Study design: this trial is a multi-central randomized controlled trial which contains 14 centers. Random sequences will be generated by the clinical evaluating center of China Academy of Chinese Medical Sciences. Subjects are patients who have severe chronic constipation.

Sample size evaluation: Sample size will be based on the proportion of patients having mean complete spontaneous bowel movements (CSBMs) no less than 3 times per week. The proportion is 31.67% in our phase I clinical trial by using electro-acupuncture, and 30.9% in another trial by using prucalopride.The total sample size is 560.

Periods and primary outcome: participants will be assessed at baseline for 2 weeks, treated for 8 weeks, and followed up for 24 weeks. Primary outcome is the proportion of patients having mean CSBMs/week no less than 3 times over the latter 6-week treatment.

Quality control: the study is a randomized controlled trial; participants were included strictly; evaluators and statisticians are blinded; quality control officers of 3 different levels will supervise this trial.

Data management: this trial will use the Remote Dara Capture (RDC) system for data entering and Data Verification Plan (DVP) for data examining.

Statistical analysis: Intention-To-Treat (ITT) analysis will be used in this study. One-sided test (non-inferiority) will be used for testing the primary outcomes; meanwhile, two-sided test will be used for evaluating other outcomes. A P value equal to or less than 0.05 is considered to indicate statistical significance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 560 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect Comparison of Electro-acupuncture and Prucalopride for Severe Chronic Constipation: a Multi-center Noninferiority Randomized Controlled Trial
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Electro-acupuncture Electro-acupuncture at bilateral ST25, SP14 ,and ST37. Patients will be treated once per day for 30 min, 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks.	Procedure: acupuncture; Electro-acupuncture at bilateral ST25, SP14 ,and ST37. Patients will be treated once per day for 30 minutes, 5 times/week for the first 2 weeks and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks.; Other Names: eletro-acupuncture
Active Comparator: Prucalopride Prucalopride Succinate taken orally, 2mg/day in the morning before breakfast	Drug: Prucalopride; Prucalopride Succinate will be taken orally at the dose of 2mg/day in the morning before breakfast. Each treatment cycle will be given for continuous 32 weeks.; Other Names: serotonin 5-HT(4) receptor agonist

Outcome Measures

Primary Outcome Measures

1. the Proportion of Participants With ≥3 Mean Weekly CSBMs Over Weeks 3-8 [over weeks 3-8 (the latter 6-week treatment)]

   Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the mean weekly CSBMs of each patient were calculated over weeks 3-8. Second, we got the number of patients with 3 or more mean weekly CSMBs. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: the latter 6 weeks of treatment (weeks 3-8).

Secondary Outcome Measures

1. the Proportion of Participants With ≥3 Mean Weekly CSBMs Over Weeks 1-2, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 11-12, 15-16, 19-20, 31-32.]

   Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the mean weekly CSBMs of each patient were calculated over weeks 1-2, 11-12, 15-16, 19-20, 31-32. Second, we got the number of patients with 3 or more mean weekly CSMBs. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: weeks 1-2, 11-12, 15-16, 19-20, 31-32.

2. the Proportion of Participants With ≥1 Increase in Mean Weekly CSBMs From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.]

   Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the increase in mean weekly CSBMs of each patient from baseline were calculated over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. Second, we got the number of patients with ≥1 increase in the mean weekly CSMBs from baseline. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

3. Mean Weekly CSBMs and Its Change From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.]

4. Mean Weekly SBMs and Its Change From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.]

5. the Change From Baseline in Mean Score of Stool Consistency for Each SBM Over Weeks 1-2 and 3-8. [over weeks 1-2, 3-8.]

   The change from baseline in the mean score of stool consistency of each SBM over weeks 1-2 and weeks 3-8. Assessing time: baseline, weeks 1-2 and weeks 3-8. Patients will self-report their stool consistency of each SBM according to the 7-type Bristol Stool Form Scale (scored by 1 to 7 respectively). Type 1: Separate hard lumps, like nuts (hard to pass); Type 2: Sausage-shaped, but lumpy; Type 3: Like a sausage but with cracks on its surface; Type 4: Like a sausage or snake, smooth and soft; Type 5: Soft blobs with clear cut edges (passed easily); Type 6: Fluffy pieces with ragged edges, a mushy stool; Type 7: Watery, no solid pieces. Entirely liquid. Type 3 and 4 were deemed as a normal stool.

6. the Change From Baseline in Mean Score of Straining for Each SBM Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.]

   The change from baseline in the mean score of straining of each SBM over weeks 1-2, 3-8, 9-12, 9-16, 9-20, 9-32. Assessing time: baseline, weeks 1-2, 3-8, 9-12, 9-16, 9-20, 9-32. Patients will self-report their straining degree of each SBM in the defecation diaries according to the following scale. 0 = not difficult; 1 = a little difficult, need some straining to defecate; 2 = difficult, need straining to defecate; 3 = very difficult, need hard straining to defecate. Higher scores mean a worse outcome.

7. Time to the First CSBMs [from the time of their first treatment to the time they having their first CSBMs]

   Abbreviation: CSBMs, complete spontaneous bowel movements. Time to the first CSBMs was counted by days. Rescue medicine or other measurements for constipation is not allowed to be used 48 hours before and after the first treatment for evaluating the time to the first complete spontaneous bowel movement. Participants were assessed after the first treatment until they having their first CSBMs.

8. Change From Baseline in Mean Score of Patient Assessment of Constipation Quality of Life [week 4 and week 8]

   The change from baseline of the score of Patient Assessment of Constipation Quality of Life (PAC-QOL) at week 4 and week 8. PAC-QOL is a self-report questionnaire to evaluate the quality of life in patients with constipation, which was distributed by Mapi Research Trust in France. This questionnaire contains 28 items including 4 basic parts of physical discomfort, worries and concerns, psychosocial discomfort, and satisfaction. We use the Chinese version in our trial. Assessing point: baseline, week 4 and week 8. The score of PAC-QOL ranged from 1 to 5 (1 indicates no discomfort or feeling very satisfied, 5 indicates extreme severity and always appears or feeling very dissatisfied).

Other Outcome Measures

1. Proportion of Patients Using Rescue Medicine Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.]

2. Average Dosage of Bisacodyl Used Weekly Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.]

3. Average Dosage of Glycerine Enema Used Weekly Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. [over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. meeting Rome Ⅲ criteria for diagnosing functional constipation;

2. severe chronic constipation (two or fewer CSBMs per week for more than 3 months）;

3. the weekly mean CSBMs are no more than 2 times during the 2-week baseline

4. aged from 18 to 75 years old

5. no use of drugs for constipation (emergency treatments should be excepted) during at least 2 weeks before enrollment; no acupuncture treatment for constipation in the previous 1 month; never joined any other trial in progress;

6. volunteered to join this research and signed the informed consent

Exclusion Criteria:

1. irritable bowel syndrome, organic constipation or secondary constipation caused by endocrine, metabolic, nervous, postoperative diseases, or by drugs;

2. mushy stool or watery stool are showed more than once during baseline when defecating spontaneously without any laxative (Bristol stool type 6 or 7);

3. history of pelvic floor dysfunction;

4. taking medicine in progress which can induce constipation;

5. severe hemorrhoid or anal fissure;

6. constipation with serious cardiovascular, hepatic or renal diseases, cognitive dysfunction, abdominal aortic aneurysm or hepatosplenomegaly, aphasia, mental disorders, or illness which affects the cooperation for examination and treatment;

7. women in gestation or lactation period;

8. blood coagulation disorders or using anticoagulants regularly such as Warfarin and Heparin;

9. cardiac pacemaker carrier.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Ministry of Science and Technology of the People´s Republic of China

Investigators

• Study Chair: Zhishun Liu, Ph.D, Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

• Liu B, Wang Y, Wu J, Mo Q, Wang W, He L, Yan S, Liu Z. Effect of electroacupuncture versus prucalopride for severe chronic constipation: protocol of a multi-centre, non-inferiority, randomised controlled trial. BMC Complement Altern Med. 2014 Jul 23;14:260. doi: 10.1186/1472-6882-14-260.

• Responsible Party: Liu Zhishun, Dean of Acupuncture Department of Guang'anmen Hospital, Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• ClinicalTrials.gov Identifier: NCT02047045
• Other Study ID Numbers: 2012BAI24B01SCC
• First Posted: Jan 28, 2014
• Last Update Posted: Mar 22, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Liu Zhishun, Dean of Acupuncture Department of Guang'anmen Hospital, Guang'anmen Hospital of China Academy of Chinese Medical Sciences: severe chronic constipation; randomized controlled; electro-acupuncture; prucalopride
• Additional relevant MeSH terms: Constipation; Prucalopride; Serotonin

Study Results

Participant Flow

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture at bilateral ST25, SP14 ,and ST37. Patients will be treated once per day for 30 min, 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. acupuncture: Electro-acupuncture at bilateral ST25, SP14 ,and ST37. Patients will be treated once per day for 30 minutes, 5 times/week for the first 2 weeks and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks.	Prucalopride Succinate taken orally, 2mg/day in the morning before breakfast Prucalopride: Prucalopride Succinate will be taken orally at the dose of 2mg/day in the morning before breakfast. Each treatment cycle will be given for continuous 8 weeks.
Period Title: Baseline
STARTED	280	280
COMPLETED	277	278
NOT COMPLETED	3	2
Period Title: Baseline
STARTED	277	278
COMPLETED	266	263
NOT COMPLETED	11	15
Period Title: Baseline
STARTED	266	263
COMPLETED	265	262
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Electro-acupuncture	Prucalopride	Total
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.	Total of all reporting groups
Overall Participants	277	278	555
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.06 (16.12)	45.79 (16.00)	45.93 (16.06)
Sex: Female, Male (Count of Participants)
Female	222 80.1%	224 80.6%	446 80.4%
Male	55 19.9%	54 19.4%	109 19.6%
Race/Ethnicity, Customized (participants) [Number]
Han	270 97.5%	275 98.9%	545 98.2%
Others	7 2.5%	3 1.1%	10 1.8%
Region of Enrollment (participants) [Number]
China	277 100%	278 100%	555 100%

Outcome Measures

1. Primary Outcome

Title	the Proportion of Participants With ≥3 Mean Weekly CSBMs Over Weeks 3-8
Description	Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the mean weekly CSBMs of each patient were calculated over weeks 3-8. Second, we got the number of patients with 3 or more mean weekly CSMBs. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: the latter 6 weeks of treatment (weeks 3-8).
Time Frame	over weeks 3-8 (the latter 6-week treatment)

Outcome Measure Data

Analysis Population Description

We recruited 560 participants (280 for each group) in total; however, 3 participants from EA group and 2 from prucalopride group withdrew their informed consents. Therefore, they were not included in the baseline analysis.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
Number [percentage of participants]	36.2 13.1%	37.8 13.6%

2. Secondary Outcome

Title	the Proportion of Participants With ≥3 Mean Weekly CSBMs Over Weeks 1-2, 11-12, 15-16, 19-20, 31-32.
Description	Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the mean weekly CSBMs of each patient were calculated over weeks 1-2, 11-12, 15-16, 19-20, 31-32. Second, we got the number of patients with 3 or more mean weekly CSMBs. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: weeks 1-2, 11-12, 15-16, 19-20, 31-32.
Time Frame	over weeks 1-2, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

We recruited 560 participants (280 for each group) in total; however, 3 participants from EA group and 2 from prucalopride group withdrew their informed consents. Therefore, they were not included in the analysis.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
weeks 1-2	27.1 9.8%	33.8 12.2%
weeks 11-12	38.3 13.8%	43.2 15.5%
weeks 15-16	38.0 13.7%	41.0 14.7%
weeks 19-20	35.7 12.9%	42.1 15.1%
weeks 31-32	37.6 13.6%	38.5 13.8%

3. Secondary Outcome

Title	the Proportion of Participants With ≥1 Increase in Mean Weekly CSBMs From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Description	Abbreviation: CSBMs, complete spontaneous bowel movements. Calculation method: First, the increase in mean weekly CSBMs of each patient from baseline were calculated over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32. Second, we got the number of patients with ≥1 increase in the mean weekly CSMBs from baseline. Third, we got the proportion of participants through dividing that number by the total cases at baseline, and multiplying by 100%. Assessing time frame: weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Time Frame	over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

We recruited 560 participants (280 for each group) in total; however, 3 participants from EA group and 2 from prucalopride group withdrew their informed consents. Therefore, they were not included in the analysis.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
weeks 1-2	49.5 17.9%	61.5 22.1%
weeks 3-8	66.4 24%	63.3 22.8%
weeks 11-12	63.5 22.9%	63.7 22.9%
weeks 15-16	65.7 23.7%	66.2 23.8%
weeks 19-20	61.4 22.2%	64.0 23%
weeks 31-32	61.0 22%	61.5 22.1%

4. Secondary Outcome

Title	Mean Weekly CSBMs and Its Change From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Time Frame	over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

We recruited 560 participants (280 for each group) in total; however, 3 participants from EA group and 2 from prucalopride group withdrew their informed consents. Therefore, they were not included in the analysis.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
weeks 1-2	1.27	1.78
weeks 3-8	1.96	1.97
weeks 11-12	2.00	2.01
weeks 15-16	1.93	2.07
weeks 19-20	1.90	2.00
weeks 31-32	1.94	1.99

5. Secondary Outcome

Title	Mean Weekly SBMs and Its Change From Baseline Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Time Frame	over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

We recruited 560 participants (280 for each group) in total; however, 3 participants from EA group and 2 from prucalopride group withdrew their informed consents. Therefore, they were not included in the analysis.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
weeks 1-2	1.85	2.91
weeks 3-8	2.13	2.60
weeks 11-12	1.87	2.43
weeks 15-16	1.65	2.38
weeks 19-20	1.59	2.33
weeks 31-32	1.50	2.24

6. Secondary Outcome

Title	the Change From Baseline in Mean Score of Stool Consistency for Each SBM Over Weeks 1-2 and 3-8.
Description	The change from baseline in the mean score of stool consistency of each SBM over weeks 1-2 and weeks 3-8. Assessing time: baseline, weeks 1-2 and weeks 3-8. Patients will self-report their stool consistency of each SBM according to the 7-type Bristol Stool Form Scale (scored by 1 to 7 respectively). Type 1: Separate hard lumps, like nuts (hard to pass); Type 2: Sausage-shaped, but lumpy; Type 3: Like a sausage but with cracks on its surface; Type 4: Like a sausage or snake, smooth and soft; Type 5: Soft blobs with clear cut edges (passed easily); Type 6: Fluffy pieces with ragged edges, a mushy stool; Type 7: Watery, no solid pieces. Entirely liquid. Type 3 and 4 were deemed as a normal stool.
Time Frame	over weeks 1-2, 3-8.

Outcome Measure Data

Analysis Population Description

The number of participants providing data of stool consistency was 270 in EA group and 266 in prucalopride group.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	270	266
weeks 1-2	0.48	0.67
weeks 3-8	0.78	0.74

7. Secondary Outcome

Title	the Change From Baseline in Mean Score of Straining for Each SBM Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Description	The change from baseline in the mean score of straining of each SBM over weeks 1-2, 3-8, 9-12, 9-16, 9-20, 9-32. Assessing time: baseline, weeks 1-2, 3-8, 9-12, 9-16, 9-20, 9-32. Patients will self-report their straining degree of each SBM in the defecation diaries according to the following scale. 0 = not difficult; 1 = a little difficult, need some straining to defecate; 2 = difficult, need straining to defecate; 3 = very difficult, need hard straining to defecate. Higher scores mean a worse outcome.
Time Frame	over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

The number of participants providing data of straining was 271 in EA group and 266 in prucalopride group over weeks 1-2/3-8; The number of participants providing data of straining was 264 in EA group and 261 in prucalopride group over weeks 11-12/15-16/19-20/31-32.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	271	266
weeks 1-2	-0.33	-0.52
week 3-8	-0.54	-0.63
weeks 11-12	-0.60	-0.58
weeks 15-16	-0.59	-0.57
weeks 19-20	-0.67	-0.67
weeks 31-32	-0.67	-0.67

8. Secondary Outcome

Title	Time to the First CSBMs
Description	Abbreviation: CSBMs, complete spontaneous bowel movements. Time to the first CSBMs was counted by days. Rescue medicine or other measurements for constipation is not allowed to be used 48 hours before and after the first treatment for evaluating the time to the first complete spontaneous bowel movement. Participants were assessed after the first treatment until they having their first CSBMs.
Time Frame	from the time of their first treatment to the time they having their first CSBMs

Outcome Measure Data

Analysis Population Description

The number of participants providing data of time to the first CSBMs was 272 in EA group and 266 in prucalopride group.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	272	266
Median (Inter-Quartile Range) [days]	4	5

9. Secondary Outcome

Title	Change From Baseline in Mean Score of Patient Assessment of Constipation Quality of Life
Description	The change from baseline of the score of Patient Assessment of Constipation Quality of Life (PAC-QOL) at week 4 and week 8. PAC-QOL is a self-report questionnaire to evaluate the quality of life in patients with constipation, which was distributed by Mapi Research Trust in France. This questionnaire contains 28 items including 4 basic parts of physical discomfort, worries and concerns, psychosocial discomfort, and satisfaction. We use the Chinese version in our trial. Assessing point: baseline, week 4 and week 8. The score of PAC-QOL ranged from 1 to 5 (1 indicates no discomfort or feeling very satisfied, 5 indicates extreme severity and always appears or feeling very dissatisfied).
Time Frame	week 4 and week 8

Outcome Measure Data

Analysis Population Description

The number of participants providing data of PAC-QOL was 261 in EA group and 260 in prucalopride group at week 4; The number of participants providing data of PAC-QOL was 261 in EA group and 257 in prucalopride group at week 8.

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	261	260
week 4	-0.71 (0.64)	-0.72 (0.69)
week 8	-1.09 (0.79)	-1.00 (0.78)

10. Other Pre-specified Outcome

Title	Proportion of Patients Using Rescue Medicine Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Time Frame	over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
weeks 1-2	13.72 5%	7.91 2.8%
weeks 3-8	19.49 7%	17.99 6.5%
weeks 11-12	9.75 3.5%	6.83 2.5%
weeks 15-16	10.47 3.8%	7.19 2.6%
weeks 19-20	10.83 3.9%	5.76 2.1%
weeks 31-32	10.11 3.6%	6.47 2.3%

11. Other Pre-specified Outcome

Title	Average Dosage of Bisacodyl Used Weekly Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Time Frame	over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
weeks 1-2	0.75	0.50
weeks 3-8	0.17	0.67
weeks 11-12	0.50	0.75
weeks 15-16	0.50	0.50
weeks 19-20	0.50	1.00
weeks 31-32	0.50	1.00

12. Other Pre-specified Outcome

Title	Average Dosage of Glycerine Enema Used Weekly Over Weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.
Time Frame	over weeks 1-2, 3-8, 11-12, 15-16, 19-20, 31-32.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
weeks 1-2	40.00	55.00
weeks 3-8	18.33	18.33
weeks 11-12	30.00	20.00
weeks 15-16	55.00	22.50
weeks 19-20	52.50	45.00
weeks 31-32	55.00	37.50

13. Post-Hoc Outcome

Title	the Proportion of Overall CSBM Responders Over Weeks 1-8
Description	A weekly CSBM responder was defined as a patient who had ≥3 CSBMs for a given week and an increase from baseline of ≥1 CSBM for that same week. An overall CSBM responder was a patient who was a weekly CSBM responder for at least 6 of the 8 treatment weeks (75%).
Time Frame	over weeks 1-8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
Number [percentage of participants]	24.91 9%	25.54 9.2%

14. Post-Hoc Outcome

Title	the Proportion of Sustained CSBM Responder Over Weeks 1-8
Time Frame	over weeks 1-8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Electro-acupuncture	Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.	Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
Measure Participants	277	278
Number [percentage of participants]	24.91 9%	24.46 8.8%

Adverse Events

Time Frame	the whole study period (34 weeks, from week -2 to week 32)
Adverse Event Reporting Description	We recruited 560 participants (280 for each group) in total; however, 3 participants from EA group and 2 from prucalopride group withdrew their informed consents. Therefore, they were not included in the analysis.
Arm/Group Title	Electro-acupuncture		Prucalopride
Arm/Group Description	Electro-acupuncture (EA) at bilateral ST25, SP14 ,and ST37. Additionally, bilateral BL33 was used for severe straining if any; DU20 and DU24 were used for patients with anxiety and depression if any. EA treatment was lasted for 30 min, and EA treatment was taken 5 times/week for the first 2 weeks, and 3 times/week for the next 6 weeks. Each treatment cycle will include 28 sessions for continuous 8 weeks. After the EA treatment is stopped, the participants will be followed up for 24 weeks.		Prucalopride Succinate was taken orally, 2mg/day in the morning before breakfast for continuous 8 weeks. Participants took electrocardiograph (ECG) at day 7 of the 8th week. Participants would take prucalopride for additional 24 weeks if no significant ECG changes (such as prolonged QT intervals) showed.
All Cause Mortality
	Electro-acupuncture		Prucalopride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Electro-acupuncture		Prucalopride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/277 (0.4%)		0/278 (0%)
Cardiac disorders
Cardiac surgery due to myocardial infarction	1/277 (0.4%)		0/278 (0%)
Other (Not Including Serious) Adverse Events
	Electro-acupuncture		Prucalopride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/277 (17.7%)		123/278 (44.2%)
Cardiac disorders
Palpitation	0/277 (0%)		12/278 (4.3%)
Gastrointestinal disorders
Nausea	1/277 (0.4%)		22/278 (7.9%)
Abdominal Pain	4/277 (1.4%)		38/278 (13.7%)
Diarrhea	4/277 (1.4%)		36/278 (12.9%)
Bloating	1/277 (0.4%)		3/278 (1.1%)
Blood-stained stools due to diarrhea	0/277 (0%)		1/278 (0.4%)
Sense of hunger	0/277 (0%)		1/278 (0.4%)
Gastritis	0/277 (0%)		1/278 (0.4%)
Emesis	0/277 (0%)		2/278 (0.7%)
Stomachache	1/277 (0.4%)		4/278 (1.4%)
Dyspepsia	0/277 (0%)		3/278 (1.1%)
General disorders
Fever	2/277 (0.7%)		4/278 (1.4%)
Faint	1/277 (0.4%)		5/278 (1.8%)
Cold	10/277 (3.6%)		25/278 (9%)
Headache	4/277 (1.4%)		34/278 (12.2%)
Dizziness	2/277 (0.7%)		20/278 (7.2%)
Distention in head	0/277 (0%)		1/278 (0.4%)
Elevated blood pressure	1/277 (0.4%)		0/278 (0%)
Toothache	1/277 (0.4%)		1/278 (0.4%)
Hepatobiliary disorders
Fatty liver	1/277 (0.4%)		0/278 (0%)
Immune system disorders
Arthrolithisis	1/277 (0.4%)		0/278 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/277 (0%)		1/278 (0.4%)
Muscle Aches	0/277 (0%)		1/278 (0.4%)
Scapulohumeral periarthritis	1/277 (0.4%)		0/278 (0%)
Foot sprain	1/277 (0.4%)		1/278 (0.4%)
Neck and shoulder pain	1/277 (0.4%)		1/278 (0.4%)
Cervical spondylosis	1/277 (0.4%)		0/278 (0%)
Sprain	1/277 (0.4%)		1/278 (0.4%)
Leg Hurt	0/277 (0%)		1/278 (0.4%)
Knee Arthritis	0/277 (0%)		1/278 (0.4%)
Knee joint pain	1/277 (0.4%)		0/278 (0%)
Soreness of waist	0/277 (0%)		1/278 (0.4%)
Low back pain	1/277 (0.4%)		4/278 (1.4%)
Lumbar disc herniation	0/277 (0%)		1/278 (0.4%)
Wrist sprain	0/277 (0%)		1/278 (0.4%)
Nervous system disorders
Dry mouth	0/277 (0%)		1/278 (0.4%)
Upper limb numbness	1/277 (0.4%)		0/278 (0%)
Psychiatric disorders
Fear or nervous	1/277 (0.4%)		0/278 (0%)
Insomnia	1/277 (0.4%)		3/278 (1.1%)
Depression	1/277 (0.4%)		0/278 (0%)
Renal and urinary disorders
High uric acid	1/277 (0.4%)		0/278 (0%)
Urinary tract infection	0/277 (0%)		1/278 (0.4%)
Pyelonephritis	1/277 (0.4%)		0/278 (0%)
Reproductive system and breast disorders
Hyperplasia of mammary glands	1/277 (0.4%)		0/278 (0%)
Dysmenorrhea	1/277 (0.4%)		2/278 (0.7%)
Premature menstruation	2/277 (0.7%)		0/278 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/277 (0.7%)		7/278 (2.5%)
Upper respiratory infection	1/277 (0.4%)		1/278 (0.4%)
Chest distress and short of breath	0/277 (0%)		1/278 (0.4%)
Pharyngalgia	1/277 (0.4%)		0/278 (0%)
Skin and subcutaneous tissue disorders
Local hematoma	2/277 (0.7%)		0/278 (0%)
Eczema	0/277 (0%)		1/278 (0.4%)
Empyrosis	1/277 (0.4%)		1/278 (0.4%)
Urticaria	1/277 (0.4%)		0/278 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.