Long-term Oral Esomeprazole for Prevention of Peptic Ulcer Rebleeding in High-risk Patients

NCT02456012 | Completed Phase 4 DMC

• 2 other identifiers: A-BR-104-007R6IIT
• Study Type: interventional
• Target: 268
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether a long-term prophylactic use of esomeprazole 20 mg twice daily or once daily has prevention effectiveness in reducing the recurrence of peptic ulcer bleeding after ulcer healed with 16-week oral esomeprazole therapy in high-risk patients whose Rockall score ≥ 6.

Conditions

Peptic Ulcer Hemorrhage

Keywords

peptic ulcer hemorrhage; comorbidity; clinical trial

Outcome Measures

Primary Outcomes (1)

• The recurrent peptic ulcer bleeding during the 1st year

  The recurrent bleeding is defined as 1) recurrent melena, haematochezia, the presence of bloody aspirates through a nasogastric tube and 2) relapse of haemodynamic instability, including systolic blood pressure \<90 mm Hg, heart rate \>120 bpm or a drop in haemoglobin concentration of \>2 g/dL, or sudden increase in transfusion requirements. For each patient with either suspected or active rebleeding, the hemoglobin level and gastroscopy are performed to confirm any blood or coffee-ground-like materials in the stomach, or the persistence of stigmata indicating recent haemorrhage. The gastroscopy also determines whether the source of rebleeding was a peptic ulcer or some other non-ulcer bleeding source, such as varices.

  52 weeks

Secondary Outcomes (2)

• The recurrence of peptic ulcer confirmed by follow-up endoscopy

  between the 17th and 52th weeks

• The recurrent peptic ulcer bleeding during the second year-and-thereafter

  Since the 2nd year to the study end

Other Outcomes (1)

• Medical events, including diarrhea and pneumonia, and bone fracture

  During the period of taking PPIs and until two weeks after discontinuing PPIs.

Study Arms (3)

The D group

EXPERIMENTAL

After 3-day intravenous 8 mg/h and 16-week oral 40 mg/day esomeprazole treatment, patients receive oral esomeprazole 20 mg twice daily for 36 weeks.

Drug: oral esomeprazole 20 mg twice daily

The S group

EXPERIMENTAL

After 3-day intravenous 8 mg/h and 16-week oral 40 mg/day esomeprazole treatment, patients receive oral esomeprazole 20 mg once daily for 36 weeks.

Drug: oral esomeprazole 20 mg once daily

The C group

NO INTERVENTION

The cohort control group includes patients from a previous study who had peptic ulcer bleeding and Rockall scores ≥ 6 but who did not receive esomeprazole or other proton pump inhibitors after 3-day intravenous 8 mg/h and 16-week oral 40 mg/day esomeprazole treatment.

Interventions

oral esomeprazole 20 mg twice daily DRUG

for 36 weeks

Also known as: Nexium®, 20 mg, AstraZeneca AB, Södertälje, Sweden

The D group

oral esomeprazole 20 mg once daily DRUG

for 36 weeks

Also known as: Nexium®, 20 mg, AstraZeneca AB, Södertälje, Sweden

The S group

Eligibility Criteria

• Age: 20 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible participants included patients ≥20 years who had undergone gastroscopy for melena, haematochezia, or haematemesis due to bleeding peptic ulcers with major stigmata of recent hemorrhage. The major stigmata of recent haemorrhage were classified as Forrest class Ia, Ib, IIa, and IIb. All of the stigmata are given one or a combination of endoscopic therapies, including local injection of diluted epinephrine 1:10000, bipolar heated probe, argon plasma coagulation, band ligation, or hemoclip therapy. Patients will undergo a follow-up endoscopy about 12 to 16 weeks later to confirm that the ulcer has healed to be less than 0.5 cm; otherwise, patients are not enrolled.

You may not qualify if:

• Patients are excluded if they had tumor bleeding or ulcer bleeding due to the presence of a Dieulafoy lesion or mechanical factors (e.g, gastrostomy tube induction), comorbid with reflux esophagitis grade C or D, Barrett's esophagus, or marginal ulcer bleeding, hypersensitivity to esomeprazole or any component of the formulation, or had previously participated in the study. Because of concern for patient safety with certain drug-drug interactions, patients who receive anti-platelet therapy, e.g., aspirin, clopidogrel, or others for prophylaxis of established cardiovascular or cerebrovascular diseases will be excluded.

Sponsors & Collaborators

• Hsiu-Chi Cheng: lead

Study Sites (1)

Helicobacter pylori study group, National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Related Publications (8)

• Chan HL, Wu JC, Chan FK, Choi CL, Ching JY, Lee YT, Leung WK, Lau JY, Chung SC, Sung JJ. Is non-Helicobacter pylori, non-NSAID peptic ulcer a common cause of upper GI bleeding? A prospective study of 977 patients. Gastrointest Endosc. 2001 Apr;53(4):438-42. doi: 10.1067/mge.2001.112840.

  PMID: 11275883 BACKGROUND

• Hung LC, Ching JY, Sung JJ, To KF, Hui AJ, Wong VW, Leong RW, Chan HL, Wu JC, Leung WK, Lee YT, Chung SC, Chan FK. Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study. Gastroenterology. 2005 Jun;128(7):1845-50. doi: 10.1053/j.gastro.2005.03.026.

  PMID: 15940620 BACKGROUND

• Chow DK, Sung JJ. Non-NSAID non-H. pylori ulcer disease. Best Pract Res Clin Gastroenterol. 2009;23(1):3-9. doi: 10.1016/j.bpg.2008.11.010.

  PMID: 19258182 BACKGROUND

• Wong GL, Wong VW, Chan Y, Ching JY, Au K, Hui AJ, Lai LH, Chow DK, Siu DK, Lui YN, Wu JC, To KF, Hung LC, Chan HL, Sung JJ, Chan FK. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009 Aug;137(2):525-31. doi: 10.1053/j.gastro.2009.05.006. Epub 2009 May 13.

  PMID: 19445937 BACKGROUND

• Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996 Mar;38(3):316-21. doi: 10.1136/gut.38.3.316.

  PMID: 8675081 BACKGROUND

• Cheng HC, Wu CT, Chang WL, Cheng WC, Chen WY, Sheu BS. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut. 2014 Dec;63(12):1864-72. doi: 10.1136/gutjnl-2013-306531. Epub 2014 Mar 21.

  PMID: 24658598 BACKGROUND

• Marmo R, Koch M, Cipolletta L, Capurso L, Grossi E, Cestari R, Bianco MA, Pandolfo N, Dezi A, Casetti T, Lorenzini I, Germani U, Imperiali G, Stroppa I, Barberani F, Boschetto S, Gigliozzi A, Gatto G, Peri V, Buzzi A, Della Casa D, Di Cicco M, Proietti M, Aragona G, Giangregorio F, Allegretta L, Tronci S, Michetti P, Romagnoli P, Piubello W, Ferri B, Fornari F, Del Piano M, Pagliarulo M, Di Mitri R, Trallori G, Bagnoli S, Frosini G, Macchiarelli R, Sorrentini I, Pietrini L, De Stefano S, Ceglia T, Chiozzini G, Salvagnini M, Di Muzio D, Rotondano G; Italian registry on upper gastrointestinal bleeding (Progetto Nazionale Emorragie Digestive--PNED 2). Predicting mortality in non-variceal upper gastrointestinal bleeders: validation of the Italian PNED Score and Prospective Comparison with the Rockall Score. Am J Gastroenterol. 2010 Jun;105(6):1284-91. doi: 10.1038/ajg.2009.687. Epub 2010 Jan 5.

  PMID: 20051943 BACKGROUND

• Chiang HC, Yang EH, Hu HM, Chen WY, Chang WL, Wu CT, Wu DC, Sheu BS, Cheng HC. An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding. BMC Gastroenterol. 2022 Oct 21;22(1):439. doi: 10.1186/s12876-022-02534-0.

  PMID: 36271335 DERIVED

MeSH Terms

Conditions

Peptic Ulcer Hemorrhage

Interventions

Esomeprazole

Condition Hierarchy (Ancestors)

Gastrointestinal Hemorrhage; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Bor-Shyang Sheu, MD

  National Cheng-Kung University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: May 25, 2015
• First Posted: May 28, 2015
• Study Start: April 1, 2015
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: February 22, 2022

Record last verified: 2022-02

Locations

TW (1)