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Erosive EsophagitisPhase 4NCT02679508

Vonoprazan Study in Patients With Erosive Esophagitis to Evaluate Long-term Safety

A Phase 4 study testing Vonoprazan and Lansoprazole in people with Erosive Esophagitis, run by Takeda at 36 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration (260 weeks: 5 years) of vonoprazan 10 mg or 20 mg in patients receiving maintenance treatment after healed erosive esophagitis (EE), and the curative effect of vonoprazan 20 mg versus… Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Erosive Esophagitis
What is being tested?
Vonoprazan and Lansoprazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
208 participants
Where
36 sitesJapan
Study dates
20 Mar 2016to 5 Mar 2022
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Healing Phase:
  • Participants endoscopically diagnosed with EE of grades A to D by the LA Classification Grading System at the start of treatment (Week 0 of the healing phase)
  • Participants with H. pylori negative
  • Participants who, in the opinion of the principal investigator or investigator, are capable of understanding the content of the clinical research and complying with the research protocol requirements.
  • Participants who can sign and date an informed consent form and information sheet prior to the conduction of the clinical research procedures.
  • Male or female participants aged 20 years or older at the time of informed consent
Show all 11Show fewer
  • Therapeutic category: Ambulatory
  • Maintenance Phase:
  • Participants who have endoscopically confirmed EE healing* (mucous membrane disorder is not observed) at completion of the healing phase (Week 4 or 8 of the healing phase)
  • Participants who are classified as grade 0 according to severity classification of EE (See Table 9.b)
  • Participants who have been determined to be appropriate as subjects for maintenance treatment of EE by the principal investigator or investigator

Who cannot join

  • Healing Phase:
  • Participants with concurrent peptic ulcer (except scarred stage) or Zollinger-Ellison syndrome
  • Participants who received treatment with PPIs (including vonoprazan) within 4 weeks (Week -4 to Week 0) prior to the start of healing phase (Week 0 of the healing phase)
  • Participants with a history of H. pylori eradication.
  • Participants who have received surgery or treatment affecting gastroesophageal reflux (fundoplication or dilation for esophageal stenosis [excluding Schatzki's ring], etc.)
  • Participants with an esophagus-related complication (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal stenosis, etc.), a history of radiotherapy or cryotherapy of the esophagus, a caustic or physiochemical trauma (esophageal sclerotherapy, etc.). However, participants with Schatzki's ring (mucosal tissue ring around inferior esophageal sphincter) or Barrett's esophagus are allowed to be included.
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  • Participants with clinically apparent hepatic impairment (e.g., AST or ALT levels at the time of informed consent: >1.5 times the upper limit of normal (ULN).
  • Participants with renal impairment or renal failure [creatinine clearance (CCr) ˂30 mL/min, etc.]
  • Participants with a history of hypersensitivity or allergy for PPIs.
  • Participants with a history of gastrectomy, gastrointestinal resection, or vagotomy
  • Participants with a malignant tumor
  • Participants who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant
  • Participants with one of the diseases listed under administration contraindication in the vonoprazan or lansoprazole package insert
  • Participants planning to take prohibited concomitant medications during the research period
  • Participants participating in other clinical studies
  • Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator
  • Maintenance Phase:
  • Participants who have taken PPIs other than the study drug or the control drug during the healing phase
  • Participants who have been determined to be inappropriate as subjects in the study by the principal investigator or investigator

Trial locations and contacts

36 sites in 1 country.

36 sites in 1 country

Japan36 sites

  • Tokatsu Tsujinaka Hospital

    Abiko, Chiba

  • Shin-Beppu Hospital

    Beppu, Oita Prefecture

  • Juntendo University Hospital

    Bunkyo-ku, Tokyo

  • Chihaya Hospital

    Fukuoka

  • Harada Hospital

    Fukuoka

  • Kimura Shiro Clinic

    Fukuoka

  • Kyushu University Hospital

    Fukuoka

  • Mori Clinic

    Fukuoka

  • Hakodate Hospital

    Hakodate, Hokkaido

  • Hohnodai Hospital National Center For Global Health and Medicine

    Ichikawa, Chiba

  • Shimane University Hospital

    Izumo, Shimane

  • Juntendo University Shizuoka Hospital

    Izunokuni, Shizuoka

  • Kawakubo Clinic

    Kama, Fukuoka

  • Aoyama Medical Clinic

    Kobe, Hyōgo

  • Hanabata Clinic

    Kumamoto

  • Morinaga Ueno Clinic

    Kumamoto

  • Kawasaki Medical University

    Kurashiki, Okayama-ken

  • Oki Hospital

    Kyoto

  • Red Cross Matsuyama Hospital

    Matsuyama, Ehime

  • Hyogo College Of Medicine

    Nishinomiya, Hyōgo

  • Arita Hospital

    Ōita

  • Asahigaoka Hospital

    Okayama

  • Kawasaki Hospital

    Okayama

  • Banno Clinic

    Ōta-ku, Tokyo

  • Masuyama Clinic

    Ōtawara, Tochigi

  • Shiga Hospital

    Ōtsu, Shiga

  • Shiga University Of Medical Science Hospital

    Ōtsu, Shiga

  • Shirane Clinic

    Sendai, Miyagi

  • Tohoku University Hospital

    Sendai, Miyagi

  • Shimokitazawa Tomo Clinic

    Setagaya-ku, Tokyo

  • National Center For Global Health and Medicine

    Shinjyuku-ku, Tokyo

  • Nippon Medical School Hospital

    Shinjyuku-ku, Tokyo

  • Matsuki Clinic

    Shizuoka

  • KKR Takamatsu Hospital

    Takamatsu, Kagawa-ken

  • Kohga Hospital

    Yaizu, Shizuoka

  • Oizumi Medical Clinic

    Yamagata

Other trials in Japan

About this study

Official title: Vonoprazan Study In Patients With Erosive Esophagitis to Evaluate Long-term Safety: A Study to Evaluate the Safety of Long-term Administration of Vonoprazan in Maintenance Treatment in Patients With Erosive Esophagitis (EE)

The purpose of this study is exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration (260 weeks: 5 years) of vonoprazan 10 mg or 20 mg in patients receiving maintenance treatment after healed erosive esophagitis (EE), and the curative effect of vonoprazan 20 mg versus lansoprazole in patients with EE.

Read the detailed description

This is a multicenter, open-label, randomized, parallel-group study to exploratorily evaluate the effect on gastric mucosal tissue and the safety of long-term administration of vonoprazan in maintenance treatment after healed EE, and the curative effect of vonoprazan versus lansoprazole in participants with EE.

Participants endoscopically diagnosed with EE of Los Angeles (LA) Classification Grades A to D at the start of treatment (Week 0 of the healing phase) will be randomly assigned to receive either vonoprazan 20 mg or lansoprazole 30 mg to be taken once daily for up to 8 weeks. Subjects with healed EE as confirmed endoscopically at Week 4 or 8 in the healing phase will enter the maintenance phase.

In the maintenance phase, the vonoprazan group and the lansoprazole group will be administered a starting dose of 10 mg and 15 mg, respectively, once daily up to 260 weeks.

If the principal investigator or investigator judged the effect of vonoprazan 10 mg or lansoprazole 15 mg to be insufficient as the maintenance treatment of EE, vonoprazan and lansoprazole may be increased to 20 mg and 30 mg, respectively.

The research period will consist of two subperiods: healing phase in which participants with EE will receive treatment (for 4 or 8 weeks) and maintenance phase in which participants will receive maintenance treatment (for 260 weeks), and thus, a total of up to 268 weeks. The number of visits will be a maximum of 18 visits. Planned number of research subjects, as the number of research subjects for entry to the maintenance phase, will be 130 participants in the vonoprazan group and 65 participants in the lansoprazole group.

Being tested
Vonoprazan, Lansoprazole
Keywords
Esophagitis
Medical subject headings
Esophagitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VonoprazanDrug

    Vonoprazan fumarate 10 mg or 20 mg capsules

  • LansoprazoleDrug

    Lansoprazole 15 mg or 30 mg capsules

Study groups in NCT02679508
Study groupRoleWhat they receive
Vonoprazan groupExperimentalVonoprazan 20 mg administered orally once daily in the healing phase + vonoprazan 10 mg (as the initial dose and adjusted to vonoprazan 10 mg or 20 mg) administered orally once daily in the maintenance phase
Receives: Drug: Vonoprazan
Lansoprazole groupActive comparatorLansoprazole 30 mg administered orally once daily in the healing phase + lansoprazole 15 mg (as the initial dose and adjusted to lansoprazole 15 mg or 30 mg) administered orally once daily in the maintenance phase
Receives: Drug: Lansoprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Malignant Alteration of Epithelial Cells

    Numbers of participants with malignant alteration of epithelial cells for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

    Measured: Time Frame: Up to Week 268 (Week 260 in Maintenance Phase)

  2. Number of Participants With Parietal Cell Protrusion/Hyperplasia

    Numbers of participants with parietal cell protrusion/hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  3. Number of Participants With Foveolar Hyperplasia

    Numbers of participants with foveolar hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  4. Number of Participants With Enterochromaffin-like-cell Hyperplasia

    Numbers of participants with enterochromaffin-like-cell hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  5. Number of Participants With G-cell Hyperplasia

    Numbers of participants with G-cell hyperplasia for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for gastric mucosa histopathology. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

Secondary outcomes (19)

  1. Percentage of Participants With Recurrence of Erosive Esophagitis (EE)

    Erosive esophagitis recurrence is defined as endoscopically confirmed to have erosive esophagitis (LA classification grades O and A to D) during the Maintenance Phase. The LA classification graded as follows- Grade O: normal mucosa; Grade A: nonconfluent mucosal breaks <5 mm in length; Grade B: nonconfluent mucosal breaks ≥ 5mm in length; Grade C: confluent mucosal breaks <75% circumferential; Grade D: confluent mucosal breaks >75% circumferential.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  2. Percentage of Participants Who Healed EE at the End of Healing Phase

    Percentage of participants who healed EE at the end of healing phase was reported.

    Measured: Up to Week 8

  3. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) in Maintenance Phase

    Number of participants reporting one or more TEAEs in Maintenance Phase was reported. An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

    Measured: 260 weeks (Baseline, up to the end of Maintenance Phase)

  4. Number of Participants With Fundic Gland Polyp

    Numbers of participants with fundic gland polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  5. Number of Participants With Hyperplastic Polyp

    Numbers of participants with hyperplastic polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  6. Number of Participants With Cobblestone Mucosa

    Numbers of participants with cobblestone mucosa for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  7. Number of Participants With Multiple White and Flat Elevated Lesions

    Numbers of participants with multiple white and flat elevated lesions for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  8. Number of Participants With Black Spots

    Numbers of participants with black spots for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as the endpoint for endoscopic findings. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  9. Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Middle Gastric Body

    Numbers of participants with inflammation (mononuclear infiltration) in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  10. Number of Participants With Inflammation (Mononuclear Infiltration) in Greater Curvature of Antrum

    Numbers of participants with inflammation (mononuclear infiltration) in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  11. Number of Participants With Neutrophilic Infiltration in Greater Curvature of Middle Gastric Body

    Numbers of participants with neutrophilic infiltration in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  12. Number of Participants With Neutrophilic Infiltration in Greater Curvature of Antrum

    Numbers of participants with neutrophilic infiltration in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  13. Number of Participants With Atrophy in Greater Curvature of Middle Gastric Body

    Numbers of participants with atrophy in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  14. Number of Participants With Atrophy in Greater Curvature of Antrum

    Numbers of participants with atrophy in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  15. Number of Participants With Intestinal Metaplasia in Greater Curvature of Middle Gastric Body

    Numbers of participants with intestinal metaplasia in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  16. Number of Participants With Intestinal Metaplasia in Greater Curvature of Antrum

    Numbers of participants with intestinal metaplasia in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  17. Number of Participants With Presence of H.Pylori in Greater Curvature of Middle Gastric Body

    Numbers of participants with presence of H.pylori in greater curvature of the middle gastric body for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  18. Number of Participants With Presence of H.Pylori in Greater Curvature of Antrum

    Numbers of participants with presence of H.pylori in greater curvature of the antrum for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported as histological assessment of gastritis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

  19. Number of Participants With Gastric Polyp

    Numbers of participants with gastric polyp for Vonoprazan group and Lansoprazole group at Week 268 (Week 260 in Maintenance Phase) were reported. The number analyzed is the number of participants with data available for analysis.

    Measured: Up to Week 268 (Week 260 in Maintenance Phase)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2016 (estimated)
  2. Study start20 Mar 2016
  3. Primary completion5 Mar 2022
  4. Study completion5 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
208 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02679508
Sponsor's protocol ID
Vonoprazan-4003
Other IDs
U1111-1178-8948, JapicCTI-163153
Status last verified
Dec 2023
First submitted
8 Feb 2016
Last updated
13 Dec 2023
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

  • Uemura N, Kinoshita Y, Haruma K, Kushima R, Yao T, Akiyama J, Aoyama N, Baba Y, Suzuki C, Ishiguro K. Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study. Clin Gastroenterol Hepatol. 2025 Apr;23(5):748-757.e5. doi: 10.1016/j.cgh.2024.08.004. Epub 2024 Aug 27.

    PubMed 39209187

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vonoprazan and Lansoprazole in people with Erosive Esophagitis, run by Takeda at 36 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Malignant Alteration of Epithelial Cells (time frame: Time Frame: Up to Week 268 (Week 260 in Maintenance Phase)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02679508, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.

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