The Efficacy of Double Doses of Oral Esomeprazole in Preventing Rebleeding for Patients With Bleeding Peptic Ulcers

Peptic Ulcer Bleeding Clinical Trial

— DDE  

Official title:

The Studies of the Pathophysiologic Mechanisms of Poor Ulcer Healing & Clinical Improvement to the High Ulcer Rebleeding Rate for Patients With Comorbid Illnesses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01591083
• Other study ID #: ER-100-008
• Status: Completed
• Phase: Phase 4
• First received: May 2, 2012
• Last updated: October 11, 2015
• Start date: August 2011
• Est. completion date: July 2014

Study information

• Verified date: October 2015
• Source: National Cheng-Kung University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 474
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 95 Years

Eligibility

Inclusion Criteria:

• Patients who received gastroscopy for melena, hematochezia, or hematemesis in whom bleeding peptic ulcers with major stigmata of recent hemorrhage are detected are consecutively enrolled. All of these major SRH are treated by local injection of diluted epinephrine 1:10000 with or without combined therapy with a heater probe, argon plasma coagulation, band ligation, or hemoclip therapy.

Exclusion Criteria:

• Patients are excluded if they had tumor bleeding or ulcer bleeding due to mechanical factors (i.e., gastrostomy tube induction), warfarin use, failure to establish hemostasis under gastroscopy, or hypersensitivity to esomeprazole or any component of the formulation.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Peptic Ulcer
• Peptic Ulcer Bleeding
• Peptic Ulcer Hemorrhage
• Ulcer

Intervention

Drug:
• esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden)
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.

Locations

Country	Name	City	State
Taiwan	National Cheng Kung University Hospital	Tainan

Sponsors (2)

Lead Sponsor	Collaborator
National Cheng-Kung University Hospital	National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recurrent bleeding		within 28 days after the first bleeding event	Yes
Secondary	the length of hospitalization		within 28 days after the first bleeidng event	No
Secondary	the amount of blood transfusion		within 28 days after the first bleeding event	Yes
Secondary	major events such as surgery or transarterial embolization		within 28 days after the first bleeding event	Yes
Secondary	the fading rate of major stigmata of recent hemorrhage	At the primary gastroscopy, the adherent clot is vigorously washed away with water jet. All of the stigmata of recent hemorrhage (SRH) are treated by one or a combination of endoscopic therapies. The success of endoscopic hemostasis is defined as cessation of bleeding together with achievement of cavitation at the vessel after application of the heater probe.; Second-look endoscopy is scheduled 48-72 hours after successful primary endoscopic hemostasis and intravenous high-dose proton pump inhibitor infusion. For each patient with either suspected or active recurrent bleeding, emergent endoscopy is conducted earlier before the schedule to confirm and treat peptic ulcer recurrent bleeding.; Multiple logistic regression analysis is applied to assess the independent risk factors related to residual major stigmata or early recurrent bleeding of peptic ulcers.	within 3 days after the first bleeding event	Yes
Secondary	mortality		within 28 days and 120 days after the first bleeding event	Yes