The Efficacy of Double Doses of Oral Esomeprazole in Preventing Rebleeding and the Selection Criteria for Second-look Endoscopy for Patients With Bleeding Peptic Ulcers
Information source: National Cheng-Kung University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Peptic Ulcer Bleeding
Intervention: esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden) (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: National Cheng-Kung University Hospital Official(s) and/or principal investigator(s): Bor-Shyang Sheu, MD, Study Director, Affiliation: National Cheng-Kung University Hospital
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Primary outcome: recurrent bleeding
Secondary outcome: the length of hospitalizationthe amount of blood transfusion major events such as surgery or transarterial embolization the fading rate of major stigmata of recent hemorrhage mortality
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 95 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
National Cheng Kung University Hospital, Tainan 704, Taiwan; Recruiting Hsiu-Chi Cheng, MD, PhD, Phone: 886-6-2353535, Ext: 4733, Email: teishuki@mail.ncku.edu.tw
Additional Information
Starting date: August 2011
Last updated: April 3, 2014
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