search
Back to results

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

Primary Purpose

Peptic Ulcer Bleeding

Status
Completed
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden)
Sponsored by
National Cheng-Kung University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peptic Ulcer Bleeding focused on measuring Peptic ulcer rebleeding, double dose of esomeprazole

Eligibility Criteria

18 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Cheng Kung University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Double oral dose

Regular oral dose

Control group

Arm Description

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 receive 40 mg oral esomeprazole twice daily for 11 days and followed by 40 mg once daily for 14 days.

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 receive 40 mg oral esomeprazole once daily for 25 days.

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 receive 40 mg oral esomeprazole once daily for 25 days.

Outcomes

Primary Outcome Measures

recurrent bleeding

Secondary Outcome Measures

the length of hospitalization
the amount of blood transfusion
major events such as surgery or transarterial embolization
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.
mortality

Full Information

First Posted
May 2, 2012
Last Updated
October 11, 2015
Sponsor
National Cheng-Kung University Hospital
Collaborators
National Science Council, Taiwan
search

1. Study Identification

Unique Protocol Identification Number
NCT01591083
Brief Title
The Efficacy of Double Doses of Oral Esomeprazole in Preventing Rebleeding for Patients With Bleeding Peptic Ulcers
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cheng-Kung University Hospital
Collaborators
National Science Council, Taiwan

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peptic Ulcer Bleeding
Keywords
Peptic ulcer rebleeding, double dose of esomeprazole

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
474 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Double oral dose
Arm Type
Active Comparator
Arm Description
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 receive 40 mg oral esomeprazole twice daily for 11 days and followed by 40 mg once daily for 14 days.
Arm Title
Regular oral dose
Arm Type
Active Comparator
Arm Description
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 receive 40 mg oral esomeprazole once daily for 25 days.
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
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 receive 40 mg oral esomeprazole once daily for 25 days.
Intervention Type
Drug
Intervention Name(s)
esomeprazole (Nexium®, AstraZeneca AB, Södertälje, Sweden)
Other Intervention Name(s)
Nexium
Intervention Description
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.
Primary Outcome Measure Information:
Title
recurrent bleeding
Time Frame
within 28 days after the first bleeding event
Secondary Outcome Measure Information:
Title
the length of hospitalization
Time Frame
within 28 days after the first bleeidng event
Title
the amount of blood transfusion
Time Frame
within 28 days after the first bleeding event
Title
major events such as surgery or transarterial embolization
Time Frame
within 28 days after the first bleeding event
Title
the fading rate of major stigmata of recent hemorrhage
Description
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.
Time Frame
within 3 days after the first bleeding event
Title
mortality
Time Frame
within 28 days and 120 days after the first bleeding event

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bor-Shyang Sheu, MD
Organizational Affiliation
National Cheng-Kung University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
704
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
31222633
Citation
Yang EH, Wu CT, Kuo HY, Chen WY, Sheu BS, Cheng HC. The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores >/= 6. Surg Endosc. 2020 Apr;34(4):1592-1601. doi: 10.1007/s00464-019-06919-3. Epub 2019 Jun 20.
Results Reference
derived
PubMed Identifier
28751088
Citation
Cheng HC, Yang EH, Wu CT, Wang WL, Chen PJ, Lin MY, Sheu BS. Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use. J Formos Med Assoc. 2018 Apr;117(4):316-325. doi: 10.1016/j.jfma.2017.07.006. Epub 2017 Jul 24.
Results Reference
derived
PubMed Identifier
24658598
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs