Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22440
Title: Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial.
Authors: Young, Paul J;Bagshaw, Sean M;Forbes, Andrew B;Nichol, Alistair D;Wright, Stephen E;Bailey, Michael;Bellomo, Rinaldo;Beasley, Richard;Brickell, Kathy;Eastwood, Glenn M;Gattas, David J;van Haren, Frank;Litton, Edward;Mackle, Diane M;McArthur, Colin J;McGuinness, Shay P;Mouncey, Paul R;Navarra, Leanlove;Opgenorth, Dawn;Pilcher, David;Saxena, Manoj K;Webb, Steve A;Wiley, Daisy;Rowan, Kathryn M
Affiliation: Intensive Care Unit, Royal Perth Hospital, Perth, Australia
University of Melbourne, Melbourne, Australia
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Intensive Care Unit, Fiona Stanley Hospital, Murdoch, Australia
Intensive Care Unit, Canberra Hospital, Canberra, Australia
Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand
Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand
Intensive Care Unit, Royal Prince Alfred Hospital, Camperdown, Australia
George Institute for Global Health, University of New South Wales, Sydney, Australia
Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation, Camberwell, Australia
Intensive Care Unit, Bankstown Hospital, Bankstown, Australia
Department of Critical Care Medicine, University of Alberta Hospital, Edmonton, Canada
Biostatistics Unit, Monash University, Melbourne, Australia
Intensive Care Unit, Alfred Hospital, Melbourne, Australia
Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
University College Dublin-Clinical Research Centre, St Vincent's Hospital, Dublin, Ireland
Medical Research Institute of New Zealand, Wellington
Intensive Care Unit, Wellington Hospital, Wellington, New Zealand
Intensive Care Unit, Freeman Hospital, Newcastle upon Tyne, England
Medical Research Institute of New Zealand, Wellington
University College Dublin-Clinical Research Centre, St Vincent's Hospital, Dublin, Ireland
Medical Research Institute of New Zealand, Wellington
Intensive Care National Audit and Research Centre, London, England
Medical Research Institute of New Zealand, Wellington
Department of Critical Care Medicine, University of Alberta Hospital, Edmonton, Canada
Intensive Care National Audit and Research Centre, London, England
Issue Date: 17-Jan-2020
EDate: 2020-01-17
Citation: JAMA 2020; online first: 17 January
Abstract: Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown. To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis. Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital. Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs). The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay. Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, -0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group. Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication. anzctr.org.au Identifier: ACTRN12616000481471.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22440
DOI: 10.1001/jama.2019.22190
ORCID: 0000-0002-1650-8939
PubMed URL: 31950977
Type: Journal Article
Appears in Collections:Journal articles

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