UMIN-CTR Clinical Trial

Public title

A Retrospective Study on the Effectiveness and Safety of Macrogol 4000, Sodium Chloride, Sodium Bicarbonate, and Potassium Chloride in Pregnant Women with Chronic Constipation

Acronym

A Retrospective Study on the Effectiveness and Safety of Macrogol 4000, Sodium Chloride, Sodium Bicarbonate, and Potassium Chloride in Pregnant Women with Chronic Constipation

Scientific Title

A Retrospective Study on the Effectiveness and Safety of Macrogol 4000, Sodium Chloride, Sodium Bicarbonate, and Potassium Chloride in Pregnant Women with Chronic Constipation

Scientific Title:Acronym

A Retrospective Study on the Effectiveness and Safety of Macrogol 4000, Sodium Chloride, Sodium Bicarbonate, and Potassium Chloride in Pregnant Women with Chronic Constipation

Region

Japan

Condition

Chronic Constipation

Classification by specialty

Gastroenterology

Obstetrics and Gynecology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the Effectiveness and Safety of Macrogol preparations in Pregnant Women with Chronic Constipation.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Comparison of the frequency of bowel movements before and after 4 weeks of treatment by Macrogol

Key secondary outcomes

Change and Comparison of the frequency of bowel movements before, after 8 weeks and the end of treatment by Macrogol
Comparison of Bristol Stool Form Scale (BSFS) before, after 4 weeks, after 8 weeks and the end of treatment by Macrogol
Comparison of CSS before, after 4 weeks, after 8 weeks and the end of treatment by Macrogol
Comparison of straining before, after 4 weeks, after 8 weeks and the end of treatment by Macrogol
Responder rates
Subpopulation analysis by patient background

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Female

Key inclusion criteria

Pregnant women over 20 years old
Patients diagnosed with chronic constipation who have less than 3 bowel movements per week
Patients who were administered Macrogol preparations for the first time between October 1, 2020 and July 31, 2021 (Concomitant use of other drugs for the treatment of constipation should be allowed)
Patients whose therapeutic benefit outweighs the risk

Key exclusion criteria

Patients who have history of Macrogol allergies
Patiants who have presence or suspicion of Intestinal obstruction , Intestinal perforation, Severe Inflammatory bowel disease(Ulcerative colitis, Crohn's disease, toxic megacolon)
Patiants who have presence or suspicion of organic constipation
Patients who received the Macrogol preparation outside the approved dosage and administration

Target sample size

80

Name of lead principal investigator

1st name	Yojiro
Middle name
Last name	Maruyama

Organization

Juntendo University Nerima Hospital

Division name

Department of Obstetrics and Gynecology

Zip code

177-8521

Address

3-1-10,Takanodai,Nerima-ku,Tokyo

TEL

03-5923-3111

Email

ymaruya@juntendo.ac.jp

Name of contact person

1st name	Yojiro
Middle name
Last name	Maruyama

Organization

Juntendo University Nerima Hospital

Division name

Department of Obstetrics and Gynecology

Zip code

177-8521

Address

3-1-10,Takanodai,Nerima-ku,Tokyo

TEL

03-5923-3111

Homepage URL

Email

ymaruya@juntendo.ac.jp

Institute

Juntendo University Nerima Hospital
Department of Obstetrics and Gynecology

Institute

Department

Personal name

Organization

MOCHIDA PHARMACEUTICAL CO.,LTD.
EA Pharma Co.,Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Juntendo University Hospital

Address

3-1-3,Hongo,Bunkyo-ku,Tokyo,113-8431

Tel

03-3813-3111

Email

gcp@juntendo-nerima.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2021

Year

12

Month

28

Day

URL releasing protocol

none

Publication of results

Published

URL related to results and publications

none

Number of participants that the trial has enrolled

36

Results

The administration of macrogol preparations to pregnant women with chronic constipation resulted in a significant increase in the frequency of bowel movements 4 weeks after administration , and the effect continued until 8 weeks. In addition, chronic constipation symptoms such as straining and stool hardness improved after 4 weeks, and the effect continued until the end of treatment. Adverse events, side effects and safety issues were not confirmed.

Results date posted

2023

Year

07

Month

28

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The average age of the patients was 35.9 years and the average gestational age of the patients was 21.4 weeks. Within 2 weeks prior to macrogol administration, 27.8% of patients had a history of treatment with constipation medicine , and 22.2% of patients were using constipation medicine.

Participant flow

The study was conducted using only existing information without obtaining new samples or information from patients.
Information on observation and examination was obtained from medical records and questionnaires for patients who were treated Macrogol during the investigation period, and the efficacy and safety of Macrogol were examined.

Adverse events

None

Outcome measures

The frequency of bowel movements before treatment was 1.98+-0.57(mean+-standard deviation, same for below), and the frequency of bowel movements after 4 weeks of treatment was 3.51+-1.58, and the change from before treatment was 1.45+-1.63(95% confidence interval:0.580 to 2.313). The frequency of bowel movements after 4 weeks of treatment significantly increased compared to before treatment (paired t-test/p=0.003).

The frequency of bowel movements after 8 weeks of treatment was 3.61+-2.06(mean+-standard deviation, same for below),and the change from before treatment was 1.81+-2.10(95% confidence interval:0.308 to 3.319). The frequency of bowel movements at the end of treatment was 3.69+-1.96 ,and the change from baseline was 1.77 +- 2.00(95% confidence interval: 0.831 to 2.703). The frequency of bowel movements after 8 weeks of treatment and at the end of treatment both increased significantly compared to before treatment.[paired t-test/ after 8 weeks of treatment:p = 0.047, at the end of treatment: p = 0.002(both of these are corrected values with Bonferroni correction.)]

Bristol Stool Form Scale was 2.07 +- 1.03 (mean +- standard deviation, same for below) before the start of treatment, 2.78+-1.13 after 4 weeks of treatment, 2.71+-1.16 after 8 weeks of treatment, and 2.77+-1.17 at the end of treatment.There was significant difference in Bristol Stool Form Scale after 4 weeks of treatment and at the end of treatment compared to before treatment[Wilcoxon signed-rank test/ after 4 weeks of treatment: p = 0.002, after 8 weeks of treatment: p = 0.064, at the end of treatment: p = 0.002 (both of these are corrected values with Bonferroni correction.)].

If the answer for each symptom score in the questionnaire is blank, the score was set to 0 and was totaled[CSS total score (lower missing data are set to 0)]. The CSS total score (lower missing data are set to 0) was 12.1 +- 3.7 (mean +- standard deviation, same for below) before treatment, and 9.4 +- 4.2 after 4 weeks of treatment. The change in the CSS total score at 4 weeks was -2.9 +- 4.8 (95% confidence interval : -5.362 to -0.402). The CSS total score (lower missing data are set to 0) after 8 weeks of treatment was 8.8 +- 3.9. The change in the CSS total score at 8 weeks was -4.0 +- 6.0 (95% confidence interval: -7.781 to -0.219). The CSS total score (lower missing data are set to 0) at the end of treatment was 8.8 +- 4.2. The change in the CSS total score until the end of treatment was -3.3+- 5.4 (95% confidence interval: -5.623 to -0.877).

There was significant difference in CSS total score at the end of treatment compared to before treatment [paired t-test/after 4 weeks of treatment: p = 0.076,after 8 weeks of treatment: p = 0.120, at the end of treatment: p = 0.029 (both of these are corrected values with Bonferroni correction.)].

The straining score was 2.7 +- 1.0 (mean +- standard deviation, same for below) before treatment, and 1.8 +- 1.0 after 4 weeks of treatment. The change of score at 4 weeks was -1.0 +- 1.5 (95% confidence interval: -2.74 to 15.00). The straining score after 8 weeks of treatment was 2.0 +- 1.0 . The change of score at 8 weeks was -0.8 +- 1.2 (95% confidence interval: -2.32 to 10.00). The straining score at the end of treatment was 1.9 +- 1.0. The change of score at the end of treatment was -0.8 +- 1.3(95% confidence interval: -2.97 to 20.00). There was significant difference in the straining score after 4 weeks of treatment and at the end of treatment compared to before treatment [paired t-test/after 4 weeks of treatment: p = 0.046,after 8 weeks of treatment: p = 0.127, at the end of treatment: p = 0.023 (both of these are corrected values with Bonferroni correction.)].

Responder rates of the frequency of bowel movements were 56.3% (9/16 patients) after 4 weeks of treatment (95% confidence interval: 29.9 to 80.2%), 50.0% (5/10 patients) after 8 weeks of treatment (95% confidence interval: 18.7% to 81.3%), and 55.0% (11/20 patients) at the end of treatment (95% confidence interval: 31.5% to 76.9%)("Responder"was defined as patients with at least 3 bowel movements per week and at least 1 bowel movements increase from baseline per week at each evaluation time point.).

As a result of subgroup analysis, in frequency of bowel movements after 4 weeks of treatment, which is the primary endpoint, the change in the frequency of bowel movements (mean +- standard deviation) from before the start of treatment was 1.31 +- 1.363 (n = 14) in patients not using constipation medicine,1.54 +- 1.640(n = 15) in patients using 2 packets of Macrogol, 1.08 +- 1.493(n = 10) in patients with middle of pregnancy (16-27 weeks), 1.67 +- 0.441 (n = 3) in patients with end of pregnancy (28 weeks or later), 1.41 +- 1.304 (n = 12) in patients at age 35 or older (elderly birth),1.33 +- 1.416 (n = 13)in patients not using constipation medicine other than Macrogol, 1.35 +- 1.454(n = 10) in patients with complications, 1.44 +- 1.683 (n = 15)in patients without hemorrhoids, 1.05 +- 0.749 (n = 9) in patients above median weight (55.95 kg), 1.39 +- 1.619(n = 10) in patients above median(3.0) straining before treatment,1.52 +- 1.653(n = 15) in patients with straining(1 or larger) before treatment,1.25+- 1.318 (n = 13) in patients with frequency of bowel movements above median(2.00/week),1.57 +- 1.858 (n = 12) in patients with Bristol Stool Form Scale of "1, 2" before treatment, 1.08 +- 0.568 (n = 4) in patients with Bristol Stool Form Scale of "3 , 4, 5" before treatment,1.00 +- 0.781 (n = 8) in patients with CSS below median(12.75) before treatment, and 1.90 +- 2.143 (n = 8) in patients with CSS above median(12.75) before treatment.
Significant increase in frequency of bowel movements was confirmed after 4 weeks of treatment in these subgroup. Overall, there was no obvious bias in the increase in the frequency of bowel movements due to patient background.

Adverse events and side effects were not confirmed.
The discontinuation rate of Macrogol was 11.1% (4/36), and none of the patients discontinued due to adverse events.
The reasons for discontinuation were insufficient effect (2.8%,1/36),hard to swallow(5.6%, 2/36),and bad taste (2.8%,1/36)

Plan to share IPD

None

IPD sharing Plan description

None

Recruitment status

Completed

Date of protocol fixation

2021

Year

09

Month

28

Day

Date of IRB

2021

Year

11

Month

01

Day

Anticipated trial start date

2021

Year

11

Month

20

Day

Last follow-up date

2022

Year

01

Month

31

Day

Date of closure to data entry

Date trial data considered complete

2022

Year

03

Month

31

Day

Date analysis concluded

Other related information

None

Registered date

2021

Year

12

Month

28

Day

Last modified on

2023

Year

09

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053057