Top Trials in Gastroenterology & Hepatology
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About this ebook
The Top Trials in Gastroenterology and Hepatology is a selection of 25 “hot” trials that have been influential in clinical practice. These trials have been critically appraised and summarized. Topics include:
- Luminal Gastroenterology
- Inflammatory Bowel Disease
- Nutrition
- Motility
- Hepatology
- Therapeutic Endoscopy
A perspective on each trial gives context and significance to the summaries, and a list of further reading identifies other influential papers.
- Mayur Brahmania, MD FRCPC, co-author
- Dustin Loomes, MD FRCPC, co-author
- Rahul Bhindi, MD, co-author
- Dana Moffatt, MD FRCPC, co-author
Mayur Brahmania
Dr. Mayur Brahmania is currently a Gastroenterologist/Hepatologist at the Toronto Western Hospital Liver Centre. Aside from clinical practice, Dr. Brahmania is involved in medical education both at the undergraduate and post-graduate level while also peer reviewing and publishing for many leading gastroenterology and hepatology journals. Dr. Brahmania’s research interests include quality improvement initiatives to advance and standardize quality of care in patients living with liver disease.
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Reviews for Top Trials in Gastroenterology & Hepatology
7 ratings1 review
- Rating: 5 out of 5 stars5/5A very interesting and short book
Such books should be published often
Book preview
Top Trials in Gastroenterology & Hepatology - Mayur Brahmania
Preface
As a learner, it is always challenging to know the background literature that forms the basis of medical knowledge in a specialty, as well as cutting-edge trials on the forefront of clinical practice. This represents a moving target since, with time, new literature is assimilated into conventional wisdom. We made this book to capture a selection of the top trials
in the fields of gastroenterology and hepatology. The trials were chosen for their important historical impact and/or for their impact on clinical practice. Included are references to supplemental papers that will enhance knowledge in a given area of practice. Ultimately, we hope this book will serve as a resource for both those interested in gastroenterology as well as those who have chosen gastroenterology as a career.
Mayur Brahmania, MD FRCPC
Dustin Loomes, MD FRCPC
Rahul Bhindi, MD CCFP
Dana Moffatt, MD FRCPC
TABLE OF CONTENTS
Luminal Gastroenterology
1. Gastrointestinal Bleeding
2. Colorectal Cancer Screening
3. Clostridium difficile
Inflammatory Bowel Disease
4. Crohn’s Disease
5. Ulcerative Colitis
6. Chronic Pouchitis
Nutrition
7. Acute Pancreatitis
8. Intestinal Failure
9. Bariatric Surgery
10. Irritable Bowel Syndrome
11. ICU Nutrition
Motility
12. Achalasia
13. Chronic Constipation
14. Acute Intestinal Pseudo-Obstruction
Hepatology
15. Hepatitis C
16. Non-Alcoholic Steatohepatitis
17. Hepatic Encephalopathy
18. Primary Biliary Cirrhosis
19. Variceal Bleeding
20. Spontaneous Bacterial Peritonitis
21. Alcoholic Hepatitis
Therapeutic Endoscopy
22. Barrett’s Esophagus
23. Post-ERCP Pancreatitis
24. Chronic Pancreatitis
25. Infected Pancreatic Necrosis
LUMINAL GASTROENTEROLOGY
Chapter 1: Gastrointestinal Bleeding
Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers
Lau JY et al. The New England Journal of Medicine. 2000; 343(5):310–316.
Question
In patients treated endoscopically for bleeding peptic ulcers, do high-dose IV proton pump inhibitors reduce the frequency of recurrent bleeding compared to placebo?
Methods
Design: Randomized controlled
Blinding: Double-blind
Follow-up Period: 30 days post randomization
Setting: Single centre (Hong Kong)
Funding: Public
Participants
Inclusion criteria:
16 years old or greater
Successful endoscopic treatment (ie, hemostasis) of actively bleeding ulcers or ulcers with non-bleeding visible vessels
Exclusion criteria:
Unsuccessful endoscopic treatment
Intervention
240 patients enrolled, with 120 randomly assigned to each group
After hemostasis achieved (endoscopic epinephrine and thermocoagulation) patients were given omeprazole 80 mg IV bolus, followed by 8 mg/hr infusion for 72 hours, followed by 20 mg PO daily for 2 weeks thereafter.
Control arm consisted of a placebo bolus and infusion for 72 hours, followed by omeprazole 20 mg PO daily x 2 weeks.
All patients with positive rapid urease test received a 1-week course of omeprazole 20 mg BID, clarithromycin 500 mg BID, amoxicillin 1 g BID and an additional 7 weeks of omeprazole 20mg PO.
Outcome
Primary endpoint:
Recurrent bleeding within 30 days after endoscopy
Secondary endpoints:
Transfusion requirements
Hospital stay
Mortality rate
Rates of surgical intervention
Results
Primary endpoint:
There was less rebleeding (8/120, 6.7%) in treatment group compared with the placebo group (27/120, 22.5%; HR=3.9).
Most rebleeding occurred during the infusion period (first 3 days), with rebleeding in 5 patients (4.2%) in treatment group vs 24 patients (20.0%; p<0.001) in placebo group.
Secondary endpoints:
Smaller mean number of blood units transfused in treatment group (2.7 vs 3.5 units; p=0.04)
Shorter duration of hospital stay in treatment group for those admitted with a GI bleed (4 days in treatment group vs 5 days in placebo group; p=0.02)
Trend towards fewer deaths within 30 days of endoscopy in treatment group (5/120, 4.2%) vs placebo group (12/120, 10.0%; p=0.13)
No significant difference in surgical interventions between the two groups
Conclusion
After endoscopic treatment of bleeding peptic ulcers, high-dose IV omeprazole bolus followed by infusion for 72 hrs reduced the rate of recurrent bleeding, the need for endoscopic retreatment, the need for blood transfusions, and shortened the length of hospitalization. There was no significant effect on mortality.
Perspective
In vitro studies have suggested that an increased pH (>6) helps to stabilize platelet aggregation and clot formation, as well as decrease clot breakdown by inhibition of pepsin. This trial was pivotal in demonstrating the benefit of omeprazole in decreasing rebleeding rates, transfusions, and length of stay; however, a clear mortality benefit was not shown.
There are still many unanswered questions: Is high dose PPI better than low dose? Is IV better than PO administration? Are there geographic differences in Asian versus non-Asian populations? An attempt to answer some of these questions in a Cochrane review of 22 RCTs did not show a statistical difference in any of these factors (1). Nevertheless, 72 hours of PPI post-endoscopic hemostasis for high-risk lesions (Forrest Ia, Ib, IIa, and IIb) is now part of routine clinical practice and is recommended by all major societal guidelines.
Further reading:
Neumann I et al. Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding.Cochrane database of systematic reviews. 2013; 6:CD007999.
Omeprazole before endoscopy in patients with gastrointestinal bleeding
Lau JY et al. The New England Journal of Medicine. 2007; 356(16): 1631–1640.
Question
Does giving omeprazole before endoscopy have any effect on the need for endoscopic therapy or improve clinical outcomes?
Methods
Design: Randomized controlled
Blinding: Double-blind
Follow-up: Day 30 post randomization
Setting: Single centre (Hong Kong)
Funding: Public
Participants
Inclusion criteria:
Consecutive patients with overt signs of upper gastrointestinal bleeding
Exclusion criteria:
Hypotensive shock refractory to resuscitation
Age <18
Unable to consent
Pregnant
Allergy to proton pump inhibitors
Long-term ASA use
Intervention
Patients were randomized to omeprazole (n=314) or placebo (n=317) and were given 80 mg IV bolus followed by IV infusion of 8 mg/hr of omeprazole or placebo, respectively, until endoscopy.
Ulcers with spurting hemorrhage, oozing hemorrhage, or non-bleeding visible vessels were injected with epinephrine (dilution 1:10,000, aliquots of 0.5 to 1 mL) followed by coaptive thermocoagulation.
Bleeding esophageal and gastric varices were treated by band ligation and injection of cyanoacrylate, respectively, plus vasoactive drugs and IV antibiotics.
Omeprazole 8 mg/hr IV infusion continued for