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