Omeprazole in Peptic Ulcer Bleeding

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Lau JYW, et al. "Effect of Intravenous Omeprazole on Recurrent Bleeding after Endoscopic Treatment of Bleeding Peptic Ulcer". The New England Journal of Medicine. 2000. 343(5):310-316.
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Clinical Question

In patients with actively bleeding peptic ulcers, what is the effect of intravenous omeprazole on bleeding recurrence after endoscopic treatment?

Bottom Line

This trial demonstrated a 70% reduction in rebleeding with intravenous omeprazole in patients with active GIB.

Major Points

Proton pump inhibitors (PPIs) have long been the mainstays of gastric acid suppression and stood as a staple in the management of GI hemorrhage. This study sought to investigate the efficacy of the intravenous PPI omeprazole in reducing rebleeding risk among patients with endoscopically-defined active GI hemorrhage. It enrolled 240 predominantly male patients with GI hemorrhage who underwent early EGD demonstrating actively bleeding ulcer or nonbleeding ulcer with visible vessel, and randomized to intravenous omepraozle or placebo. Omeprazole reduced the 30-day risk of rebleeding by 70% compared with placebo; it also reduced the need for blood transfusion and was associated with a shorter hospitalization.

Design

  • Single center, double-blinded, parallel-group, randomized, placebo-controlled trial
  • N=240
    • Omeprazole (n=120)
    • Placebo (n=120)
  • Setting: Prince of Wales Hospital, Chinese University of Hong Kong
  • Enrollment: May 1998 to July 1999
  • Analysis: Intention-to-treat

Population

Inclusion Criteria

  • Age ≥16 years
  • Admitted with upper gastrointestinal bleeding
  • Underwent endoscopy <24 hours after admission
  • Actively bleeding ulcers or ulcers with nonbleeding visible vessels

Exclusion Criteria

  • Ulcers with clean bases or flat pigments did not receive endoscopic treatment
  • Unsuccessful endoscopic treatment with profuse bleeding underwent immediate surgery
  • Terminal cancer

Baseline Characteristics

Comparisons are omeprazole vs. placebo.

  • Mean age: 64 vs. 67 years
  • Male: 67%
  • Hemoglobin: 9.4 vs. 9.5 g/dL
  • Shock at presentation: 13% vs. 12%
  • Location of ulcer:
    • Stomach: 44% vs. 40%
    • Duodenum: 54% in each
    • Stoma: 2% vs. 6%
  • Endoscopic signs of bleeding:
    • Spurting hemorrhage: 12% vs. 8%
    • Oozing hemorrhage: 42% vs. 41%
    • Nonbleeding visible vessel: 32% vs. 30%
    • Clot with underlying vessel: 15% vs. 22%
  • High-risk ulcer:
    • Posterior duodenal: 14% vs. 13%
    • Lesser-curvature: 10% vs. 4%
    • Angula incisura: 9% in each
  • Mean ulcer size: 1.2 vs. 1.1cm
  • Large ulcer (≥2cm): 18% vs. 21%
  • History of PUD: 32% vs. 38%
  • Prior ulcer bleeding: 30% in each
  • Recent H2 blocker or PPI: 2%
  • Risk factors for PUD:
    • H. pylori: 65% vs. 53%
    • NSAIDs: 33% in each
    • Aspirin: 19% vs. 15%
    • Coumadin: 4% in each

Interventions

  • At endoscopy, gastroduodenal ulcers with spurting hemorrhage, oozing hemorrhage, or nonbleeding visible vessels were injected with epinephrine and coaptive thermocoagulation was performed to achieve hemostasis.
  • After endoscopic treatment, patients were randomly assigned to receive either:
    • Omeprazole, 80mg bolus, then continuous infusion of 8mg/hr for 72 hours
    • Placebo
  • Recurrent bleeding defined as:
    • Vomiting fresh blood
    • Shock (SBP <90 mmHg or HR >110bpm) with melena after stabilization
    • Drop in hemoglobin >2g/dL within 24 hours after transfusion to a level of 10g/dL
  • Recurrent bleeding confirmed:
    • If ulcer was actively bleeding (spurting or oozing hemorrhage)
    • If there was either coffee-ground material or fresh blood in the stomach near a vessel
  • At end of infusion, all patients were given omeprazole 20mg PO daily for 8 weeks and then standard dose of 20mg orally daily for remaining seven weeks.
  • Patients with a positive rapid urease test received one-week course of H. pylori treatment with omeprazole 20mg PO BID, clarithromycin 500mg PO BID, amoxicillling 1g PO BID.

Outcomes

Comparisons are omeprazole vs. placebo.

Primary Outcomes

Recurrent bleeding by day 30
6.7% vs. 22.5% (RR 0.30; P<0.001)
Actively bleeding ulcers
4.7% vs. 17.2% (RR 0.27; P=0.04)
Ulcers with nonbleeding visible vessels
8.9% vs. 27.4% (RR 0.32; P=0.02)
Recurrent bleeding by day 3
4.2% vs. 20% (RR 0.21; P<0.001)
Recurrent bleeding by day 7
5.8% vs. 21.7% (RR 0.27; P<0.001)

Secondary Outcomes

Required surgery
2.5% vs. 7.5% (RR 0.33; P=0.14)
Median hospital stay <5 days
46.7% vs. 31.7% (RR 1.5; P=0.02)
Duration of hospitalization (median)
4 vs. 5 (P=0.006)
Units of blood transfused
2.7 vs. 3.5 (P=0.04)
Death within 30 days
4.2% vs. 10% (RR 0.42; P=0.13)
Ulcer healing at 8 weeks
85% vs. 93% (RR 0.91; P=0.14)

Funding

Supported in full by a grant from the Research Grants Council of the Hong Kong Special Administration Region.