The Efficacy of Double Doses of Oral Esomeprazole in Preventing Rebleeding for Patients With Bleeding Peptic Ulcers
Condition: Peptic Ulcer Bleeding
MeSH terms: Peptic Ulcer; Peptic Ulcer Hemorrhage; Ulcer; Hemorrhage
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients with comorbidities have an increased risk of ulcer re-bleeding, especially within
      the 14 days after first bleeding event. Three-day high dose esomeprazole infusion can prevent
      peptic ulcer rebleeding after endoscopic therapy. However, the optimal dose of oral
      esomeprazole is uncertain, especially for high risky patients. This study is to test whether
      a double dose of oral esomprazole could reduce peptic ulcer rebleeding for patients with
      Rockall score ≥ 6. Additionally, the second aim of this prospective study was to identify the
      selection criteria to predict poor fading and residual major stigmata of recent hemorrhage
      (SRH) or early recurrent bleeding after successful endoscopic hemostasis and high-dose PPI
      infusion.
    

Detailed description: 
      Peptic ulcer bleeding is a common and lethal disease, and the recurrent bleeding is an
      independent risk factor leading to the mortality. The recurrent bleeding of peptic ulcers is
      related to the presence of the stigmata of recent hemorrhage (SRH). The fading time of SRH is
      around 3 to 6 days, therefore, the recurrent bleeding develops within 2-3 days after first
      bleeding episode. The aim of acute treatment of peptic ulcer bleeding is to reduce recurrent
      bleeding by using anti-secretory drugs. Accordingly, the common duration of omeprazole
      infusion is applied as 3 days after the endoscopic therapy. Moreover, recurrent bleeding is
      also positively linked with the presence of co-morbidities. In general, patients with
      underlying medical co-morbidities have increased rates of recurrent bleeding and longer
      duration in risk of recurrent bleeding than those without co-morbidity.

      Nonetheless, even with continuous infusion of omeprazole for 3 days, recurrent bleeding rates
      remain high in certain patients such as those with the presence of underlying medical
      co-morbidities. Moreover, the duration of peptic ulcer recurrent bleeding is elongated up to
      the 14th day after the first bleeding episode in patients with co-morbidities. To prevent
      recurrent bleeding in such high risk patients, we showed therapeutic benefit for the
      prolonged course of 7-day low-dose intravenous omeprazole, which exerts better recurrent
      bleeding control than just 3-day high-dose infusion.

      The intragastric 24-h median pH is 4.9 in patients with oral 40 mg omeprazole once daily,
      which is significantly higher than baseline pH in healthy subjects. However, gastric acid
      secretion is not suppressed completely during 24 hours with oral omeprazole 40 mg once daily.
      Several studies have shown that oral high-dose PPI is equally effective in raising the
      intragastric pH more than 6 and reducing recurrent bleeding as the intravenous route.

      Hence, this study aims to test whether a higher dose of oral esomeprazole, which is more
      effective in maintaining favorable intragastric pH, could effectively reduce ulcer rebleeding
      in patients with comorbidities. This data will show the originality and clinical importance
      of a higher dose of oral esomeprazole for such high-risk patients with comorbidities with
      peptic ulcer bleeding.

      Additionally, endoscopic treatment plus a 3-day intravenous proton pump inhibitor infusion is
      the standard protocol for treatment of peptic ulcer bleeding. Moreover, several studies have
      shown that PPI treatment prior to endoscopy could decrease the presentation of SRH and the
      need of endoscopic hemostasis. However, there are insufficient data to validate the efficacy
      of such standard treatment to fade the SRH. Therefore, several studies looked at the efficacy
      of routine second-look endoscopy, defined as scheduled repeat endoscopy after primary
      endoscopic hemostasis in patients at high risk of rebleeding. However, the role of
      second-look endoscopy and the selection criteria for patients who require second-look
      endoscopy remain uncertain. There is a pressing need to elucidate the role of second-look
      endoscopy in patients with peptic ulcer bleeding after high-dose PPI infusion.

      Hence, the second aim of this prospective study is to identify the selection criteria to
      predict poor fading and residual major SRH or early recurrent bleeding after successful
      endoscopic hemostasis and high-dose PPI infusion. This data will show the originality and
      clinical importance to identify the risk factors to predict poor fading of SRH after current
      standard treatment and the patients who are indicated to receive second-look endoscopy.
    

Intervention name(s): esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden)
Intervention type(s): Drug
Intervention description(s): Each enrolled patient receives an 80 mg loading dose of intravenous esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden) immediately after hemostasis was achieved spontaneously or by gastroscopy. Patients then received a 3-day continuous high dose (8 mg per hour) of esomeprazole infusion. Then, patients with Rockall score >=6 are randomized into the double oral dose group and the regular oral dose group. Patients with Rockall score <6 are assigned to the control group.
In the double oral dose group, patients receive 40 mg oral esomeprazole twice daily for 11 days and followed by 40 mg once daily for 14 days. In the other two groups, patients receive 40 mg oral esomeprazole 40 mg once daily for 25 days.
Other intervention name(s): Nexium
Intervention MeSH terms: Esomeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Peptic ulcer rebleeding, double dose of esomeprazole