The Therapeutic Role of Intravenous Albumin Administration for Peptic Ulcer Bleeding Patients With Hypoalbuminemia

The Therapeutic Role of Albumin Supply on Peptic Ulcer Bleeding and the Correlation Between Clinical Course and Expression of Serum Response Factor on Ulcer Tissue and Superoxide Free Radical in Blood

To test whether intravenous albumin can decrease the rebleeding rate or shorten the duration of hospitalization in patients with peptic ulcer bleeding and hypoalbuminemia.

Study Overview

• Status: Completed
• Conditions: Hypoalbuminemia; Peptic Ulcer Bleeding
• Intervention / Treatment: Drug: Omeprazole; Drug: Human albumin

Detailed Description

Peptic ulcer bleeding is a common but potentially lethal disease. Recurrent bleeding is an independent risk factor for mortality. Inhibition of gastric acid secretion by intravenous proton pump inhibitor infusion can have a positive impact on the prevention of ulcer rebleeding after successful endoscopic therapy. However, the rebleeding rate can still be high in patients with comorbid illnesses even after proton pump inhibitor usage. Hypoalbuminemia has been reported to be a significant predictor of poor prognosis in patients with comorbid illnesses. Low serum albumin levels are associated with poor prognosis of wound healing and peptic ulcer bleeding; therefore, it is worthy to conduct a head-to-head comparison to validate whether administration of albumin can be helpful in improving the control of bleeding peptic ulcers, especially in patients with comorbid illnesses.

The albumin level may reflect upstream pathologic processes, such as stress or co-morbidities. Albumin administration may interrupt the downstream chain of poor outcome and thus maintain a favorable homeostasis in critically ill patients, and reduce morbidity. However, the clinical benefit of controlling peptic ulcer bleeding with exogenous albumin remains uncertain, and thus administration of albumin is not widely applied. Accordingly, the investigators conducted this pilot intervention to test whether short-term exogenous albumin administration can improve the control of peptic ulcer bleeding in hypoalbuminemic patients, who are at high risk of recurrent bleeding.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 39 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical presentations of melena, hematochezia, or hematemesis
• Gastroscopy confirmed peptic ulcers and major stigmata of recent hemorrhage
• A Rockal score ≥ 6

Exclusion Criteria:

• Gastric or esophageal, or duodenal tumor bleeding
• Ulcer due to mechanical factors
• Warfarin use
• Failure to establish hemostasis under gastroscopy
• Hypersensitivity to omeprazole, esomeprazole, albumin or any component of the formulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal albumin group; Based on the serum albumin level at enrollment, the patients were assigned into the normal albumin group if their serum albumin ≥ 30 g/L. Patients in this group receive intravenous omeprazole treatment.	Drug: Omeprazole; After endoscopic hemostasis, each enrolled patient received an 80 mg loading dose of intravenous omeprazole (Losec®, AstraZeneca, Sweden) immediately. Patients then received a 3-day continuous omeprazole infusion in dosage of 80 mg per day. After omeprazole infusion, oral esomeprazole (Nexium®, AstraZeneca, Sweden) 40 mg per day was given in the normal albumin group and the intervention group until the end of follow-up. After omeprazole infusion, oral omeprazole (Losec®) 20 mg per day was given in the cohort control group until the end of follow-up.; Other Names: Losec®, AstraZeneca, Sweden
Experimental: Intervention group; Based on the serum albumin level at enrollment, the patients were assigned into an intervention group if their serum albumin < 30 g/L. Patients in this group receive both Human albumin and intravenous omeprazole.	Drug: Omeprazole; After endoscopic hemostasis, each enrolled patient received an 80 mg loading dose of intravenous omeprazole (Losec®, AstraZeneca, Sweden) immediately. Patients then received a 3-day continuous omeprazole infusion in dosage of 80 mg per day. After omeprazole infusion, oral esomeprazole (Nexium®, AstraZeneca, Sweden) 40 mg per day was given in the normal albumin group and the intervention group until the end of follow-up. After omeprazole infusion, oral omeprazole (Losec®) 20 mg per day was given in the cohort control group until the end of follow-up.; Other Names: Losec®, AstraZeneca, Sweden; Drug: Human albumin; Each patient in the intervention group received Human Albumin 20%® (ZLB Behring, Marburg, Germany), immediately. The dosage of albumin infusion was 10 g q8h for 1 day in patients with albumin levels ranging from 25 g/L to 29 g/L or 2 days in those with albumin levels < 25 g/L.; Other Names: Human Albumin 20%®, ZLB Behring, Marburg, Germany
Experimental: Cohort control group; The study also included 29 patients with peptic ulcer bleeding and with hypoalbuminemia (serum albumin level < 30 g/L), but without receiving albumin supply from our previous study to serve as the cohort control group. Patients in this group receive intravenous omeprazole treatment.	Drug: Omeprazole; After endoscopic hemostasis, each enrolled patient received an 80 mg loading dose of intravenous omeprazole (Losec®, AstraZeneca, Sweden) immediately. Patients then received a 3-day continuous omeprazole infusion in dosage of 80 mg per day. After omeprazole infusion, oral esomeprazole (Nexium®, AstraZeneca, Sweden) 40 mg per day was given in the normal albumin group and the intervention group until the end of follow-up. After omeprazole infusion, oral omeprazole (Losec®) 20 mg per day was given in the cohort control group until the end of follow-up.; Other Names: Losec®, AstraZeneca, Sweden

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
peptic ulcer rebleeding	rebleeding was defined as: (i) continuous melena, hematochezia, or the presence of recurrent bloody aspirates through the naso-gastric tube; and (ii) relapse of hemodynamic instability, including systolic blood pressure < 90 mm Hg, heart rate >120 beats per min, or a hemoglobin drop by more than 20 g/L. For each patient with either suspected or active rebleeding of peptic ulcer, gastroscopy was conducted to confirm that the bleeding source was either a peptic ulcer or other non-ulcer conditions.	within 28 days after the first bleeding event

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the length of hospitalization	the length of hospitalization after the first bleeding episode and the length of hospitalization after peptic ulcer rebleeding	within 28 days after the first bleeding event
the number of units of blood transfused		during the 28-day period after admission to the emergency room or after the presence of gastrointestinal bleeding signs in patients with nosocomial bleeding
the number of participants with massive rebleeding events in need of transarterial embolization or emergency surgery		within 28 days after the first bleeding event

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Collaborators: National Science Council, Taiwan
• Investigators: Principal Investigator: Hsiu-Chi Cheng, MD, PhD, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 20, 2013
• First Submitted That Met QC Criteria: March 27, 2013
• First Posted (Estimate): April 2, 2013

Study Record Updates

• Last Update Posted (Actual): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 27, 2019
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: peptic ulcer; hospitalization; hypoalbuminemia; rebleeding
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Hematologic Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Blood Protein Disorders; Duodenal Diseases; Hypoproteinemia; Gastrointestinal Hemorrhage; Ulcer; Hemorrhage; Peptic Ulcer; Hypoalbuminemia; Peptic Ulcer Hemorrhage; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: ER-98-239