Oral Versus IV Proton Pump Inhibitor in High-risk Bleeding Peptic Ulcers After Endoscopic Hemostasis

Oral Versus Intravenous Proton Pump Inhibitor Treatment in High-risk Bleeding Peptic Ulcers After Endoscopic Hemostasis: a Prospective Randomized Comparative Study

Endoscopic hemostasis has been documented by a number of clinical studies to be effective in decreasing rebleeding, need for emergency surgery, and hospitalization days. Studies showed adjuvant treatment with proton pump inhibitor (PPI) after initial endoscopic hemostasis reduced recurrent ulcer bleeding. However, the optimal dose and route of adjuvant PPI therapy remains controversial. A recent study demonstrated frequent oral PPI offered similar acid control as currently recommended intravenous infusion PPI did in patients with bleeding ulcers. The investigators hypothesize that an frequent oral PPI treatment has similar benefit as proton pump inhibitor infusion in patient with bleeding ulcers after combined endoscopic hemostasis.

Study Overview

• Status: Unknown
• Conditions: Peptic Ulcers
• Intervention / Treatment: Drug: Pantoprazole (Pantoloc); Drug: Lansoprazole (Takepron OD)

Detailed Description

Acute peptic ulcer bleeding remains a therapeutic challenge with significant morbidity and mortality. Endoscopic therapy using various modalities significantly reduces re-bleeding, need for surgery and mortality in patients with peptic ulcer bleeding. Endoscopic therapy achieves successful hemostasis in more than 90% of patients, and re-bleeding occurs in 10-30% of patients. Re-bleeding has an important impact on prognosis. Studies showed adjuvant treatment with proton pump inhibitor (PPI) after initial endoscopic hemostasis reduced recurrent ulcer bleeding. Two consensus documents have endorsed a high-dose PPI regimen (80 mg stat followed by an infusion of 8 mg/h for 72 h). The biologically plausible mechanism of benefit of such a high-dose regimen is to promote clot stability by sustaining the intragastric pH above 6. However, the optimal dose and administration route of proton pump inhibitors (PPI) for the prevention of peptic ulcer rebleeding remains unclear.

The use of IV PPIs adds significantly to the cost of patient care in hospital. Recent studies reported oral PPI may have similar acid suppressive effect as high dose PPI infusion. A prospective trial and a retrospective analysis have shown that oral PPI therapy may also be effective in decreasing rebleeding rates in patients with acute gastrointestinal bleeding due to high-risk peptic ulcer disease, and the magnitude of benefit appears similar to what has been demonstrated with IV PPIs. A meta-analysis reported no difference in the magnitude of risk reduction between the oral- and the intravenous-route. Given the significant cost savings over their IV counterparts, oral PPIs would be an attractive choice of therapy in this situation provided that they have a similar efficacy to IV PPIs. However, no studies have directly compared oral and IV PPI therapy in this setting.

We conducted a head-to-head study, comparing two strategies for PPI administration in the prevention of rebleeding, surgery, and death in patients with high-risk bleeding peptic ulcers in whom successful endoscopic hemostasis was achieved.

• Study Type: Interventional
• Enrollment (Anticipated): 190
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chieh-Chang Chen, MD; Phone Number: 2200 88655323911; Email: chiehchang.chen@gmail.com

Study Locations

• Taiwan
  • Dou-liou, Taiwan
    • Recruiting
    • National Taiwan Univeristy Hospital Yunlin Branch
    • Contact: Chieh-Chang Chen, MD; Phone Number: 88655323911; Email: chiehchang.chen@gmail.com
  • Taipei, Taiwan
    • Not yet recruiting
    • National Taiwan Univeristy Hospital
    • Contact: Jyh-Ming Liou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18
• Confirmed ulcer bleeding with Forrest Ia, Ib, IIa
• Endoscopic hemostasis achieved by combined endoscopic hemostasis
• Informed consent obtained

Exclusion Criteria:

• No consent
• Unsuccessful endoscopic treatment
• Upper GI malignancy
• History of subtotal gastrectomy
• Bleeding tendency, platelet count < 80x109/L, prothrombin time INR >1.5
• Myocardial infarction or cerebrovascular accident within one week
• Ulcer bleeding because of mechanical factors (such as, induction of NG tube)
• Malignancy or other advanced disease with a life expectancy of < 6 months
• IV PPI > 40mg within 24hrs before enrollment
• Decompensated liver cirrhosis
• Requiring dialysis
• Pregnant or lactating women
• History of allergy or severe side effects to lansoparzole or pantoprazole

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: IV PPI; Pantoprazole 3.3mg/hr for 72hrs	Drug: Pantoprazole (Pantoloc); Pantoprazole (Pantoloc) 3.3mg/hr for 72hrs
EXPERIMENTAL: Oral PPI; Lansoprazole (Takepron OD) 30mg PO q12h	Drug: Lansoprazole (Takepron OD); Lansoprazole (Takepron OD) 30mg q12h PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical rebleeding	Clinical rebleeding defines: Hematemesis, fresh blood in the NG tube aspirate; Hematochezia/melena after a normal stool; Decrease in Hb >= 2 g/dL or an increase in Hb < 1 g/dL during 24 hrs, despite >=2 units of blood transfused during 24 hours; SBP <= 90 mm Hg or HR >= 110 beats/min AND melena/hematemesis	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality rate	30 days
Blood transfusion	30 day
Need of surgery	30 days
Lengths of hospital stay	30 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chieh-Chang Chen, MD, National Taiwan University Hospital Yunlin Branch

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ANTICIPATED): August 1, 2013

Study Registration Dates

• First Submitted: August 12, 2010
• First Submitted That Met QC Criteria: August 16, 2010
• First Posted (ESTIMATE): August 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): June 21, 2012
• Last Update Submitted That Met QC Criteria: June 20, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Oral PPI treatment has similar benefit as proton pump inhibitor infusion in patient with bleeding ulcers after combined endoscopic hemostasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Duodenal Diseases; Gastrointestinal Hemorrhage; Ulcer; Hemorrhage; Peptic Ulcer; Peptic Ulcer Hemorrhage; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole; Pantoprazole
• Other Study ID Numbers: 201003039M