Clinical trial NCT00045799: Safety & Efficacy of Omeprazole Sodium Bicarbonate for the Prevention of Upper GI Bleeding in the Critically Ill
Official title: Safety & Efficacy of Omeprazole Sodium Bicarbonate for the Prevention of Upper GI Bleeding in the Critically Ill
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Upper Gastrointestinal Bleeding
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2002-09-11
Enrollment: 354
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists
state: Arizona
city: Phoenix
country: United States
facility: Maricopa Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists, Ltd
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Burbank
country: United States
facility: Providence St. Joseph's Medical Center
state: California
city: Burbank
country: United States
facility: Verdugo Hills Hospital
state: California
city: Loma Linda
country: United States
facility: Loma Linda Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Newark
country: United States
facility: Christiana Hospital
state: Delaware
city: Brandon
country: United States
facility: PAB Clinical Research
state: Florida
city: Gainesville
country: United States
facility: Shands Hospital at the University of Florida
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Miami VAMC
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: USF Pulmonary Research
state: Florida
city: Austell
country: United States
facility: Protocare Trials
state: Georgia
city: Marietta
country: United States
facility: Wellstar Kennestone Hospital
state: Georgia
city: Elk Grove Village
country: United States
facility: Protocare - Alexian Brothers Center for Clinical Research
state: Illinois
city: Oak Park
country: United States
facility: West Suburban Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Kansas City
country: United States
facility: Department of Medicine
state: Kansas
city: New Orleans
country: United States
facility: Medical Center of LA at New Orleans (LSU Health Sci Ctr)
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University
state: Louisiana
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Truman Medical Center Hospital Hill
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: St. Johns Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Camden
country: United States
facility: Cooper Hospital/UMC
state: New Jersey
city: Elizabeth
country: United States
facility: Trinitas Hospital
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Newark
country: United States
facility: University Hospital
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Health Science Center
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: St. Vincent's Catholic Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron General Hospital
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Fort Worth
country: United States
facility: North Texas Affiliated Medical Group
state: Texas
city: Odessa
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Richmond
country: United States
facility: Pulmonary & Critical Care
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Hospitals, Inc
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: