Effects of Enteral Nutrition on Stress Ulcer Hemorrage. Multicenter Randomized Controlled Trial

Effects of Enteral Nutrition on Stress Ulcer Hemorrage. Multicenter Randomized Controlled

Enteral nutrition can provides prophylaxis against stress ulcer bleeding in critically ill patients and there may be no need to use acid suppressing drugs for stress ulcer bleeding prophylaxis in these patients. Half of the patients on enteral nutrition will not receive any acid suppressing drugs while other half receives it. They will be followed for gastrointestinal bleeding.

Study Overview

• Status: Unknown
• Conditions: Enteral Nutrition; Stress Ulcer Prophylaxis; Proton Pump Inhibitor; Gastro Intestinal Bleeding
• Intervention / Treatment: Other: enteral nutrition only; Drug: enteral nutrition + proton pump inhibitor

Detailed Description

Mucosal erosions can occur on luminal surface of stomach in approximately 75-100% patients during the first 24 hours of intensive care unit admission. These erosions often cause bleeding with penetrating superficial capillaries. Clinically significant bleeding (Significant decrease in blood pressure or decrease in hemoglobin level of more than 2 g / dL) appears to be less than 5% in ICU patients.

Enteral nutrition (EN) has protective effects against stress ulcer bleeding by neutralizing the acidic pH in the stomach lumen, providing a structural and functional integrity of the mucosal surface and trophic effect on the GI mucosa. These effects have been shown in some studies. The above-mentioned studies are inadequate for clinicians to make suggestions for relation between enteral nutrition and stress ulcer hemorrhage.

The risk factors for stress ulcer hemorrhage are mechanical ventilation, coagulopathy and burns.

Proton pump inhibitors (PPI) and histamine receptor blockers (H2RB) are the main drugs used for stress ulcer bleeding prophylaxis.

Studies have shown that 90% of patients admitted to intensive care units receive prophylaxis for stress ulcer bleeding.

Drugs (H2RB, PPI) used for prophylaxis against stress ulcer bleeding have some undesirable harmful effects in critical illnesses. These drugs, which suppress gastric acid secretion, can cause hospital-associated pneumonia and Clostridium difficile enterocolitis.

The studies, for clinical proposals are generally performed in the 1980s and early 1990s. Oral intake was stopped in most of the critically ill patients and early enteral nutrition was not widely used at the time of these major studies performed. Patients who are receiving EN have been shown to develop less stress ulcer bleeding in some studies. In a limited number of animal studies, enteral feeding has been shown to protect stress-related mucosal damage in the gastric mucosa.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kurat Gundogan, MD; Phone Number: 21919 +90 352 207 6666; Email: kgundogan@erciyes.edu.tr

Study Locations

• Turkey
  • Kayseri, Turkey, 38039
    • Recruiting
    • Erciyes University Medical School

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 years or older
• Admission to ICU
• Expected to stay in ICU >24 hours
• No contraindications to EN within the first 24 hours after admission to the intensive care unit

Exclusion Criteria:

• Evidence of active GI bleeding during current hospitalization prior to study entry
• Coagulopathy (PLT<50.000, INR>1.5, aPTT>2xcontrol)
• Patients receiving acid suppressing drugs prior to admission
• Pregnancy or lactation
• History/documented gastric ulcer
• Burn>30% body surface area
• Head injury or increased intracranial pressure
• Partial or complete gastrectomy
• Shock
• Multi-system trauma
• Exposure to gastric irritant drugs
• Patients not giving informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enteral nutrion only	Other: enteral nutrition only; Critically ill patients receiving any form of enteral nutrition will be included into the study. The patients will be randomized either enteral nutrition only group or enteral nutrition and proton pump inhibitors group. This group will receive only enteral nutrition.
Other: Enteral nutrion + proton pump inhibitor	Drug: enteral nutrition + proton pump inhibitor; Critically ill patients receiving any form of enteral nutrition will be included into the study. The patients will be randomized either enteral nutrition only group or enteral nutrition and proton pump inhibitors group. This group will receive enteral nutrition and proton pump inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GI bleeding	Overt GI bleeding (presence of coffee ground emesis hematemesis, melena or hematochezia. Significant GI bleeding, defined by 3-point decrease in hematocrit within 24 hours accompanied by overt GI bleeding or by an unexplained 6-point decrease in hematocrit during any 48 hour period.	Subjects will be followed from date of randomization until discharge from the ICU or cessation of enteral nutrition up to four weeks

Collaborators and Investigators

• Sponsor: TC Erciyes University

Publications and helpful links

General Publications

• Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, Winton TL, Rutledge F, Todd TJ, Roy P, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994 Feb 10;330(6):377-81. doi: 10.1056/NEJM199402103300601.
• Daley RJ, Rebuck JA, Welage LS, Rogers FB. Prevention of stress ulceration: current trends in critical care. Crit Care Med. 2004 Oct;32(10):2008-13. doi: 10.1097/01.ccm.0000142398.73762.20.
• Cook DJ, Reeve BK, Guyatt GH, Heyland DK, Griffith LE, Buckingham L, Tryba M. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA. 1996 Jan 24-31;275(4):308-14.
• Raff T, Germann G, Hartmann B. The value of early enteral nutrition in the prophylaxis of stress ulceration in the severely burned patient. Burns. 1997 Jun;23(4):313-8. doi: 10.1016/s0305-4179(97)89875-0.
• Ephgrave KS, Kleiman-Wexler RL, Adair CG. Enteral nutrients prevent stress ulceration and increase intragastric volume. Crit Care Med. 1990 Jun;18(6):621-4. doi: 10.1097/00003246-199006000-00009.
• Shorr LD, Sirinek KR, Page CP, Levine BA. The role of glucose in preventing stress gastric mucosal injury. J Surg Res. 1984 Apr;36(4):384-8. doi: 10.1016/0022-4804(84)90115-x.
• Pingleton SK, Hadzima SK. Enteral alimentation and gastrointestinal bleeding in mechanically ventilated patients. Crit Care Med. 1983 Jan;11(1):13-6. doi: 10.1097/00003246-198301000-00005.
• Pisegna JR. Pharmacology of acid suppression in the hospital setting: focus on proton pump inhibition. Crit Care Med. 2002 Jun;30(6 Suppl):S356-61. doi: 10.1097/00003246-200206001-00003.
• Lin PC, Chang CH, Hsu PI, Tseng PL, Huang YB. The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med. 2010 Apr;38(4):1197-205. doi: 10.1097/CCM.0b013e3181d69ccf.
• Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009 May 27;301(20):2120-8. doi: 10.1001/jama.2009.722.
• Cunningham R, Dale B, Undy B, Gaunt N. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. J Hosp Infect. 2003 Jul;54(3):243-5. doi: 10.1016/s0195-6701(03)00088-4.
• Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004 Jul 6;171(1):33-8. doi: 10.1503/cmaj.1040876.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Anticipated): August 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): March 31, 2017

Study Record Updates

• Last Update Posted (Actual): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 27, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Hemorrhage; Ulcer; Gastrointestinal Hemorrhage; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Proton Pump Inhibitors
• Other Study ID Numbers: 2016/427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No