Safety & Efficacy of Omeprazole Sodium Bicarbonate for the Prevention of Upper GI Bleeding in the Critically Ill

Critically ill patients are at an increased risk of having upper gastrointestinal (GI) bleeding due to stress related mucosal damage. Cimetidine, delivered continuously through intravenous infusion, is the only drug that the FDA has approved for the prevention of upper GI bleeding in critically ill patients. The present trial is intended to assess the safety and efficacy of an omeprazole sodium bicarbonate immediate-release suspension in this indication.

Study Overview

• Status: Completed
• Conditions: Upper Gastrointestinal Bleeding
• Intervention / Treatment: Drug: Omeprazole sodium bicarbonate immediate release PWD/FS; Drug: Cimetidine IV

Detailed Description

This trial will be a triple-blind, double-dummy, prospective, multicenter, randomized clinical trial comparing the effectiveness of OSB-IR to the effectiveness of intravenous cimetidine in preventing upper GI bleeding at risk for SRMD.

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36617
      • University of South Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Maricopa Medical Center
    • Phoenix, Arizona, United States, 85013
      • Arizona Pulmonary Specialists, Ltd
    • Phoenix, Arizona, United States, 85006
      • Arizona Pulmonary Specialists
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare
  • California
    • Berkeley, California, United States, 94705
      • Alta Bates Summit Medical Center
    • Burbank, California, United States, 91505
      • Providence St. Joseph's Medical Center
    • Burbank, California, United States, 91505
      • Verdugo Hills Hospital
    • Loma Linda, California, United States, 92354
      • Loma Linda Medical Center
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Hospital
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Gainesville, Florida, United States, 32610
      • Shands Hospital at the University of Florida
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital
    • Miami, Florida, United States, 33125
      • Miami VAMC
    • Tampa, Florida, United States, 33606
      • USF Pulmonary Research
  • Georgia
    • Austell, Georgia, United States, 30106
      • Protocare Trials
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Protocare - Alexian Brothers Center for Clinical Research
    • Oak Park, Illinois, United States, 60302
      • West Suburban Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Health Care
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Department of Medicine
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Medical Center of LA at New Orleans (LSU Health Sci Ctr)
    • Shreveport, Louisiana, United States, 71130
      • Louisiana State University
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Hennepin County Medical Center
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center Hospital Hill
    • Saint Louis, Missouri, United States, 63109
      • Washington University School of Medicine
    • Springfield, Missouri, United States, 65804
      • St. Johns Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital/UMC
    • Elizabeth, New Jersey, United States, 07207
      • Trinitas Hospital
    • Morristown, New Jersey, United States, 07960
      • Morristown Memorial Hospital
    • Newark, New Jersey, United States, 07103
      • University Hospital
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Health Science Center
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10011
      • St. Vincent's Catholic Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Akron General Hospital
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health & Science University
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University
  • Texas
    • Fort Worth, Texas, United States, 76104
      • North Texas Affiliated Medical Group
    • Odessa, Texas, United States, 79763
      • Texas Tech University Health Sciences Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Pulmonary & Critical Care
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospitals, Inc
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients will be included in the trial if they meet all of the following criteria:

1. An adult or adolescent (greater than or equal to 16 years of age) male or non-pregnant female requiring mechanical ventilation for greater than or equal to 48 hours.
2. An anticipated ICU stay of greater than or equal to 72 hours.
3. An Acute Physiology and Chronic Health Evaluation (APACHE II) score of >11 immediately before randomization.

4. At least one other risk factor for upper GI bleeding due to stress-related mucosal damage in addition to mechanical ventilation. Acceptable "other" risk factors include:

   • closed-head injury
   • multiple trauma to head, chest, abdomen, solid organs, or limbs
   • major surgical procedures (eg, mastectomy, pancreatectomy, cardiovascular surgery) 24 hours previous to screening
   • extensive burns (greater than or equal to 30% of the body surface area)
   • acute renal failure (urine output <0.5 mL/kg of body weight/hr for one hour, despite adequate fluid resuscitation)
   • acid-base disorder (pH less than or equal to 7.3 or base deficit greater than or equal to 5.0 mMol/L with a plasma lactate level >1.5 times the upper limit of normal for the reporting laboratory)
   • coagulopathy (a platelet count <50,000/mm3, an INR of >1.5 [i.e., prothrombin time >1.5 times the control value], or a partial-thromboplastin time >2.0 times the control value)
   • marked jaundice (defined as plasma total bilirubin concentration of >51.3 micromol/L or >3 mg/dL)
   • coma
   • hypotension (either a systolic blood pressure <80 mm Hg for 2 hours or more or a decrease of greater than or equal to 30 mm Hg in the systolic blood pressure)
   • shock (arterial blood pressure less than or equal to 90 mm Hg or mean arterial pressure less than or equal to 70 mm Hg for at least one hour despite adequate fluid resuscitation, adequate intravascular volume status or the use of vasopressors in an attempt to maintain a systolic blood pressure of greater than or equal to 90 mm Hg or a mean arterial pressure of greater than or equal to 70 mm Hg)
   • sepsis (defined as a positively cultured or clinically diagnosed infection with at least three of the following: a body temperature of greater than or equal to 38 degrees C [greater than or equal to 100.4 degrees F] or less than or equal to 36 degrees C [less than or equal to 96.8 degrees F], a heart rate of greater than or equal to 90 beats/min, tachypnea manifested by a respiratory rate of greater than or equal to 20 breaths/min, or hyperventilation as indicated by a PaCO2 of less than or equal to 32 mm Hg, and a white blood cell count of greater than or equal to 12,000 cells/mm3 or less than or equal to 4,000 cells/mm3, or the presence of >10% bands)
5. An intact stomach and a nasogastric or an orogastric tube in place.
6. An anticipation of no enteral feedings for the first two days of trial drug treatment.

Exclusion Criteria

Patients will be excluded from trial participation if they meet any of the following criteria:

1. A status of "No Cardiopulmonary Resuscitation (CPR)".
2. If >48 hours has elapsed since the patient became eligible for the trial.
3. Known history of vagotomy, pyloroplasty, gastroplasty, or any other gastric surgery.
4. Known allergy to cimetidine or omeprazole.
5. Active GI bleeding (including esophageal and gastric variceal bleeding, duodenal and gastric ulcers).
6. Significant risk of swallowing blood (i.e., severe facial trauma, oral lacerations, hemoptysis).
7. Enteral feedings for the first two days of trial drug treatment.
8. Use of an investigational drug within 30 days prior to randomization.
9. Critical/intensive care unit admission following esophageal, gastric, or duodenal surgery or trauma.
10. Known history of upper gastrointestinal lesions that are likely to bleed (e.g., esophageal or gastric varices, gastric polyps, tumors, etc. but excluding patients with gastric or duodenal ulcer disease).
11. Any medical or surgical condition that precludes administration of an oral medication (i.e., OSB-IR).
12. End stage liver disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Omeprazole sodium bicarbonate immediate release PWD/FS	Drug: Omeprazole sodium bicarbonate immediate release PWD/FS
ACTIVE_COMPARATOR: Cimetidine IV	Drug: Cimetidine IV

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Study Completion (ACTUAL): May 1, 2003

Study Registration Dates

• First Submitted: September 9, 2002
• First Submitted That Met QC Criteria: September 10, 2002
• First Posted (ESTIMATE): September 11, 2002

Study Record Updates

• Last Update Posted (ACTUAL): November 25, 2019
• Last Update Submitted That Met QC Criteria: November 21, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Hemorrhage; Gastrointestinal Hemorrhage; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Omeprazole; Cimetidine; Omeprazole, sodium bicarbonate drug combination
• Other Study ID Numbers: OSB-IR C03