Long-term Oral Esomeprazole for Prevention of Peptic Ulcer Rebleeding in High-risk Patients
Condition: Peptic Ulcer Hemorrhage
MeSH terms: Peptic Ulcer; Peptic Ulcer Hemorrhage; Ulcer; Hemorrhage
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      This study is conducted at the inpatient wards of National Cheng Kung University Hospital, a
      tertiary health care center in Tainan, and Kaohsiung Medical University Hospital in Kaohsiung
      City, Taiwan. All participants give written informed consent before enrollment. Each enrolled
      patient receives an 80 mg loading dose of intravenous esomeprazole (Nexium®, AstraZeneca AB,
      Södertälje, Sweden) immediately after achieving haemostasis by gastroscopy. Patients then
      receive a 3-day continuous high-dose (8 mg/h) esomeprazole infusion and then receive 40 mg
      oral esomeprazole twice daily for 11 days and once daily for following 98 days. The total
      duration of intravenous and oral esomeprazole is 16 weeks. After gastroscopy to confirm
      enrollment eligibility and ulcer healed, all patients are assessed using the Rockall risk
      scoring system at the primary endoscopy. Patients with Rockall scores ≥ 6 are randomized into
      the double-dose (D) group or the single-dose (S) group following simple randomization
      procedures with a 1:1 allocation ratio according to the result by the investigator who draw
      an envelope from a large box of sealed envelopes each containing a written code designating
      the D group or the S group. Patients in the D group and S groups receive 20 mg oral
      esomeprazole twice daily or once daily for 36 weeks, respectively. 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 16-week proton
      pump inhibitor treatment.

      One investigator generates the random allocation sequence and enrolls the participants and a
      different investigator assigns participants to interventions. The endoscopists and staff who
      check hemoglobin levels, hemodynamic status, melena, hematochezia or the aspirates through a
      nasogastric tube are blinded to the study group allocation. All enrolled patients are
      included in the intention-to-treat (ITT) analysis, but patients who are lost to follow-up,
      discontinued intervention because of adverse events, have a protocol violation or die are
      excluded from the per-protocol (PP) analysis of the primary endpoint.

      The range of co-morbidities evaluated by the Rockall scores include disseminated malignant
      diseases, liver disease (liver cirrhosis, Child-Pugh A, B, or C), renal disease (end-stage
      renal disease, chronic kidney disease or acute kidney injury with estimated glomerular
      filtration rates <30 ml/min [a score of 3 for co-morbidity], or between 30 ml/min and 60
      ml/min [a score of 2 for co-morbidity]), heart disease (congestive heart failure, New York
      Heart Association Function I to IV or coronary artery disease). Other serious co-morbidities
      include lung disease (chronic obstructive pulmonary disease, pulmonary tuberculosis,
      pneumonia or empyema), rheumatoid arthritis, sepsis, new onset cerebrovascular accident or
      recent history of any major surgery (on the thorax, abdomen, central nervous system, long
      bones or spinal bones) requiring general anesthesia within 14 days before bleeding.

      The estimated rebleeding rate within 12 months in the cohort control group is about 15% based
      on the previous study. The investigators want to be able to detect a difference between the
      cohort control group and the D group, in which the rebleeding rate is proposed to be 2%,
      equal to patients with H. pylori ulcers after eradication. The ratio of the patient number in
      each experiment group (the D group and the S group) to the patient number in the control
      group is 2:5. With a two-side α value of 0.05 and power of 80% (β=0.20), the total number of
      patients required is 54 in each experiment group and 135 in the control to detect a
      difference between the two groups. Assuming the rate of loss follow-up is 10%, 60 patients in
      each experimental group are enrolled. The investigators use a nominal 0.05 rate of the p
      value. Data related to baseline characteristics and end points are evaluated using the
      Student t test, Pearson's χ2 test or Fisher's exact test and the Mann-Whitney U test. In the
      survival analysis, the log-rank test is used to compare the Kaplan-Meier curves among the
      three study groups. All tests are two-tailed and p values of less than 0.05 indicate
      significant differences.
    

Intervention name(s): oral esomeprazole 20 mg twice daily; oral esomeprazole 20 mg once daily
Intervention type(s): Drug; Drug
Intervention description(s): for 36 weeks; for 36 weeks
Other intervention name(s): Nexium®, 20 mg, AstraZeneca AB, Södertälje, Sweden; Nexium®, 20 mg, AstraZeneca AB, Södertälje, Sweden
Intervention MeSH terms: Esomeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: peptic ulcer hemorrhage; comorbidity; clinical trial