UMIN-CTR Clinical Trial

Public title

Reflux Symptom Development After Discontinuation of Acid suppressors in Reflux-Esophagitis

Acronym

Reflux Symptom Development After Discontinuation of Acid suppressors in Reflux-Esophagitis

Scientific Title

Reflux Symptom Development After Discontinuation of Acid suppressors in Reflux-Esophagitis

Scientific Title:Acronym

Reflux Symptom Development After Discontinuation of Acid suppressors in Reflux-Esophagitis

Region

Japan

Condition

reflux esophagitis

Classification by specialty

Gastroenterology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Change of frequency and grade of GERD symptom after discontinuation of a Proton Pump Inhibitor in Reflux-Esophagitis is exploratory investigated.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

Investigate the correlation between FSSG total score change and H. pylori infection, pepsinogen I / II ratio, bloody gastrin value, sex, age, BMI, smoking, esophageal hiatal hernia.

Key secondary outcomes

Number of days to symptom onset. (symptoms diary)
Investigate factors on affecting GSRS score including subscale, FSSG (reflux, motility) score, and HADS (depression) score value of change exploratory.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Numbered container method

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Intervention: For measurement of blood gastrin, blood H. pylori antibody, blood pepsinogen, 3 ml of blood is collected from subjects registered before drug withdrawal. Also, ask the subject to fill out GSRS, FSSG, HADS questionnaire as a symptom questionnaire, hand the patient's diary for symptomatic investigation to the subject, and ask the subject to fill in before bedtime everyday. Symptoms brought during visit 4 weeks after the questionnaire and symptom diary were collected from the subjects and 3 ml of blood was collected for each gastrin measurement from the subjects. After completing the survey of the subject, the researcher records the patient's background in the questionnaire and keeps it with the symptom questionnaire (GSRS, FSSG, HADS). Participating facilities other than our university will send blood specimens and survey forms to the secretariat.

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

Male and Female

Key inclusion criteria

(1) Reflux esophagitis of LA grade A or B.
(2) Patients undergoing treatment for more than 1 month at maintenance therapy for reflux esophagitis of Acid inhibitors (H2 receptor antagonist, proton pump inhibitor, potassium competitive acid blocker).
(3) Patient with FSSG total score less than 8 points.
(4) aged 20 years or older. Gender does not matter
(5) Patients agreeing to participate in this study

Key exclusion criteria

1.Refractory reflux esophagitis which resistant treatment for more than 4 weeks with PPI or P-cab
2.Patients with peptic ulcer
3.Patients in need of treatment due to functional dyspepsia, irritable bowel syndrome, inflammatory bowel disease complicated.
4.Patients with Zollinger-Ellison syndrome, advanced atrophic gastritis (Kimura Takemoto classification: O3) or malignant anemia.
5.Patients with a history of upper gastrointestinal resection or vagotomy.
6.Patients with warning findings such as vomiting, gastrointestinal bleeding (including findings of hematemesis, venous drainage, anemia, etc.), suddenly weight loss.
7.Patients with malignant finding confirmed or suspected
8.Patients in need of treatment (PPI, P-cab, H2RA, Gastrointestinal motility drug including Rikkunshito, Anticholinergic, Antidepressant, anxiolytic, Steroid excluding external preparations , Regular use of NSAID, aspirin preparation including low dose aspirin, bisphosphonate, calcium RA) during the study period.
9.Patients complicated with severe liver disease, kidney disease, heart disease etc.
10.Other patients who are considered inappropriate for study by investigaters

Target sample size

150

Name of lead principal investigator

1st name	Kazuhide
Middle name
Last name	Higuchi

Organization

Osaka Medical College

Division name

Second Department of Internal Medicine

Zip code

569-8686

Address

2-7 Daigaku-machi, Takatsuki, Osaka, Japan

TEL

072-683-1221

Email

Higuchi@osaka-med.ac.jp

Name of contact person

1st name	Toshihisa
Middle name
Last name	Takeuchi

Organization

Osaka Medical College

Division name

Endoscopy Center

Zip code

569-8686

Address

2-7 Daigaku-machi, Takatsuki, Osaka, Japan

TEL

072-683-1221

Homepage URL

Email

in2097@osaka-med.ac.jp

Institute

Osaka Medical College

Institute

Department

Personal name

Organization

Astra Zeneca K.K

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Osaka Medical college Mishima Minami Hospital, Hirata city Hospital, Hokusetsu General Hospital, Daiichi Towakai Kai Hospital, Ishikiri-Seiki Hospital, Shitenno-ji Hospital, Aoyama Hospital, Hanwa Sumiyoshi General Hospital, Shiroyama Hospital, Seikeikai Hospital, Tatsumi Hospital, Sousei Hospital, Taisho Hospital, Keijinkai Moriguchi Hospital, Katsuragi Hospital, Midorigaoka Hospital, Osaka Kaisei Hospital, Kashiba-seiki Hospital, Rakusai Shimizu Hospital, Otowa Hospital

Name of secondary funder(s)

Organization

Osaka Medical College

Address

2-7 Daigaku-machi, Takatsuki, Osaka, Japan

Tel

072-683-1221

Email

rinri@osaka-med.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

大阪医科大学病院(大阪府)

Date of disclosure of the study information

2018

Year

01

Month

15

Day

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTs051180209

Publication of results

Partially published

URL related to results and publications

https://www.keiso-comm.com/giweek2022/index.html

Number of participants that the trial has enrolled

92

Results

Consideration of background factors is unlikely to be required in the discontinuation of
maintenance therapy for erosive GERD. There was no significant difference in the extent of disease or frequency of recurrence during the discontinuation period, regardless of whether the drug before discontinuation was a PPI or VPZ.

Results date posted

2022

Year

05

Month

19

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The inclusion criteria were:(1) GERD patients diagnosed as grade A/B minor mucosal injury by Los Angeles (LA) classification on upper gastrointestinal endoscopy, (2) patients treated with ASIDs at maintenance doses for more than 1 month, and (3) patients whose symptoms had improved to a total score of less than 8 in the subsequent retrospective questions on a patient self-completion questionnaire for the Frequency Scale for the Symptoms of GERD (FSSG)

Participant flow

This is a multicenter, open-label, interventional, exploratory study to determine the frequency and severity of recurrence of gastrointestinal symptoms after discontinuation of ASIDs for erosive GERD and to explore factors that may influence the symptoms. The Gastrointestinal Endoscopy Center at Osaka Medical and Pharmaceutical University Hospital lead to this study from November 2017 to November 2020. The ethics committee of each institution reviewed the protocol. Upon obtaining permission, the study was conducted in accordance with the Declaration of Helsinki and the Japanese Guidance on Clinical Trials, and the subjects were fully informed about the study in advance and provided written informed consent.

Adverse events

no adverse events

Outcome measures

Blood pepsinogen I and II levels including I/II ratio and blood H. pylori antibodies were measured at the time of withdrawal, and blood gastrin levels were measured at the initiation of withdrawal and Week 4
after withdrawal. The subjects were handed sheets of FSSG, Gastrointestinal Symptom Rating Scale (GSRS), and Hospital Anxiety and Depression Scale (HADS) at the withdrawal, and asked to complete the sheets at the initiation of withdrawal and Weeks 1, 2, 3, and 4. The symptom questionnaires were
collected at the visit after Week 4. The survey items in the questionnaires and case reports are those described in Table 1 in addition to types/dosage of ASIDs, gastrointestinal drugs other than ASIDs, concomitant drugs, antiplatelet drugs excluding low-dose aspirin, anticoagulants, steroids, and bisphosphonates. The intake of drugs including gastroprokinetic agents and antagonists of PPI, P-CAB, and H2 -receptor affecting the study results were prohibited.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

11

Month

01

Day

Date of IRB

2017

Year

12

Month

25

Day

Anticipated trial start date

2018

Year

01

Month

15

Day

Last follow-up date

2021

Year

01

Month

14

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

11

Month

13

Day

Last modified on

2022

Year

11

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034163