The Impact of Rabeprazole-based Triple Therapy Plus Bismuth for First-line Helicobacter Pylori Eradication on the Vaginal Microecology Change: a Prospective, Randomized Controlled Trial
Conditions: Helicobacter Pylori Infection, Helicobacter Pylori Eradication Antibiotic
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study Protocol
Official Title ：The impact of rabeprazole-based triple therapy plus
bismuth for first-line Helicobacter pylori eradication on the vaginal
microecology change: a prospective, randomized controlled trial
NCT number：None
Version No.: V1.0
Version Date: March 24, 2023

1. Research Background
Helicobacter pylori (H. pylori) is closely associated with
chronic gastritis, peptic ulcer, gastric cancer, and gastric MALT
lymphoma, and is classified as a Class I carcinogen. Both the
6th National Consensus Conference on Helicobacter pylori in
China and the Maastricht ⅥConsensus Conference have
proposed that "H. pylori gastritis is an infectious disease, and H.
pylori-infected individuals should undergo H. pylori eradication
unless there are countervailing factors." Currently, guidelines in
China recommend bismuth-containing quadruple therapy as the
preferred treatment regimen, and selecting an antibiotic regimen
with a low resistance rate is conducive to improving the
eradication rate. In recent years, multiple studies have shown
that Hp eradication therapy has short-term or long-term effects
on
the
gastrointestinal
microecology.
Gastrointestinal
microorganisms and their metabolites affect human health by
participating in host endocrine, metabolism, inflammatory
responses,
and
other
pathways.
The
female
vaginal
microecosystem
is
part
of
the
human
microecosystem,
consisting of vaginal microbial flora, endocrine regulatory
system, vaginal anatomical structure, and local immune system.
The vaginal microbial flora is diverse, with mutual symbiosis

and antagonism, influenced by various internal and external
factors, and participates in forming a complex microecosystem.
When the vaginal microecological balance is disrupted, changes
characterized by abnormal vaginal flora and abnormal vaginal
pH value may occur, leading to decreased vaginal resistance to
pathogenic microorganisms and secondary infections. To date,
there have been no domestic or international research reports on
the impact of H. pylori eradication therapy on the female
vaginal microecology. Therefore, this study intends to conduct a
clinical controlled trial among women of childbearing age and
menopausal women to explore the effect of H. pylori eradication
therapy on the vaginal microecology.
1. Research Objectives
1) Clarify the impact of H. pylori eradication therapy on the
female vaginal microecology;
2) Analyze the safety of the research protocol.
2. Research Design and Methods
(I) Research Method This is a randomized, controlled clinical
study. The total research duration of the project is 12 months,
starting from the date of ethical approval and completion of
clinical
registration.
The
research
subjects
are
patients
diagnosed
with
H.
pylori-positive
chronic
gastritis
by

gastroscopy due to relevant symptoms. A total of 72 such
patients are planned to be enrolled for H. pylori eradication
therapy, divided into two groups: women of childbearing age
and menopausal women, with 36 cases in each group, to explore
the impact of H. pylori eradication therapy on the vaginal
microecology.
(II) Case Selection 1) Inclusion Criteria Randomly select
treatment-naive patients with chronic gastritis and positive H.
pylori
confirmed
by
gastroscopy.
According
to
a
computer-generated random number table, 72 patients meeting
the inclusion criteria are randomly assigned to the standard H.
pylori quadruple therapy group (36 cases in each subgroup). All
patients participating in the study voluntarily sign the informed
consent form. ①Female, aged 18-70 years; ②Positive for H.
pylori; ③No use of PPI, H2 receptor antagonists, antibiotics,
or bismuth agents within 4 weeks; ④No prior formal H. pylori
treatment. 2) Exclusion Criteria ①Use of antibiotics or
bismuth agents within 4 weeks before treatment, or use of PPI
or H2 receptor antagonists within 2 weeks before treatment; ②
History of gastroduodenal surgery; ③Concurrent presence of
other severe diseases such as cardiac, hepatic, or renal
insufficiency, malignant tumors, and other serious internal

diseases; ④Allergy to any component of the study drugs; ⑤
Pregnant or lactating women; ⑥Participation in other drug
studies within 3 months before treatment; ⑦Inability of the
patient to clearly express their main complaints or cooperate
with the study. 3) Diagnostic Method for H. pylori Infection
Before treatment, urea breath test or histological examination of
gastric antrum mucosa is performed to assess the H. pylori
infection status. Patients with a positive result in either test are
diagnosed
as
Hp-infected.
(III)
Treatment
Protocol
1)
Treatment Groups: Total enrolled cases: 72 Treatment regimen:
Rabeprazole 10mg BID, course of treatment: 14 days Colloidal
Bismuth
Pectin
220mg
BID
Amoxicillin
1.0g
BID
Clarithromycin 0.5g BID Remarks: All drugs used in the study
are
guaranteed
to
be
from
the
same
manufacturer.
-
Clarithromycin: Klacid, Abbott Laboratories (Shanghai) Co.,
Ltd. - Amoxicillin: Nomoling, CSPC Zhongnuo Pharmaceutical
(Shijiazhuang)
Co.,
Ltd.
-
Rabeprazole:
Pariet,
Eisai
Pharmaceutical Co., Ltd. - Colloidal Bismuth Pectin: Bismuth
Pectin, Shanxi Ant Biological Pharmaceutical Co., Ltd. 2)
Research Flowchart Hp-positive chronic gastritis patients →H.
pylori
quadruple
eradication
therapy
→
Postmenopausal
women / Women of childbearing age →Vaginal microecology

testing (before treatment, 2 weeks after treatment, 8 weeks after
treatment; 6-8 weeks after the end of treatment)
3. Sample Size Calculation
Reference parameters for sample size calculation in this study: δ
(non-inferiority margin): -10%, α (significance level) = 0.025
(one-sided), statistical power (1-β) = 0.80 This study is designed
with a 1:1 sample ratio between the two groups. Combined with
references, SAS 9.2 software (SAS Institute Inc., Cary, NC) is
used to calculate that each group requires at least 33 cases.
Considering a dropout rate not exceeding 8%, n = 33 / 0.92 ≈36.
Therefore, at least 72 eligible subjects need to be enrolled.
4. Data Management and Confidentiality
Design and description related to data entry and management:
Researchers collect relevant patient information and fill in CRF
forms. After data aggregation, a designated person reviews and
verifies the data before entering it into the research database.
Confidentiality measures for patient data: All records related to
the
identity of
subjects
are
kept
confidential, and
such
information will not be disclosed to the public beyond the scope
permitted by relevant laws and/or regulations.
5. Informed Consent

The informed consent form is signed in writing by the
researcher when the patient visits and before planning to
participate in the clinical study. The informed consent form and
its explanation process shall use language and characters
understandable to the subject or their legal representative.
During the informed consent process, the researcher shall
provide detailed explanations for any content that the subject
does not understand or any questions raised about the study, and
allow the subject sufficient time to consider whether to
participate in the clinical study. After the candidate subject has
fully read and understood the content of the informed consent
form, if he/she agrees to participate in the clinical study, the
subject or their legal representative shall sign and date the
informed
consent
form,
and
the
researcher
or
their
representative who conducts the informed consent process shall
also sign and date the form. If neither the subject nor their legal
representative is literate, a witness shall be present during the
entire informed consent process. After detailed explanation of
the
informed
consent
form,
the
subject
or
their
legal
representative gives verbal consent, and the witness signs and
dates the form.
6. Adverse Event Reporting

Various adverse events: Timely measures shall be taken for
handling, and the events shall be recorded in the case report
form. Serious Adverse Events (SAE): Timely measures shall be
taken for handling, and the events shall be recorded in the case
report form. The researcher decides whether to discontinue or
reduce the dosage of the drug, and immediately reports to the
Ethics Committee, the drug clinical trial institution, and the
sponsor. A report shall be submitted to the national and
provincial food and drug regulatory authorities within 24 hours.
SAEs must be reported through the "Hospital Intranet Adverse
Event and Near-Miss Non-Punitive Reporting System". Specific
process: see the figure below. [Figure Description: Occurrence
of a serious adverse event (events requiring hospitalization,
prolonged
hospitalization,
disability,
impairment
of
work
capacity,
life-threatening
conditions,
death,
congenital
malformation, etc.) →If no emergency treatment is needed / If
emergency treatment is needed, report immediately →Report
within 24 hours to the Hospital Medical Affairs Department (Tel:
3880, 3881; for night calls, dial the general duty phone: 660000)
→Responsible for proper handling →Report to the State Drug
Administration's
Safety
Supervision
Department
for
Drug
Research Supervision (Tel: 010-88363228), Provincial Food and

Drug Administration Registration Department (Tel: 88903275),
Ethics Committee, and Sponsor/CRO (Tel: 87783969) →
Report to the Adverse Event and Near-Miss Non-Punitive
Reporting System via the hospital intranet →Follow up and
summarize handling opinions →Report to the hospital's senior
management]