Importance 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. Objective To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis. Design, Setting, and Participants 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. Interventions 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). Main Outcomes and Measures 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. Results 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. Conclusions and Relevance 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. Trial Registration anzctr.org.au Identifier: ACTRN12616000481471.

中文翻译：

---

使用质子泵抑制剂与组胺 2 受体阻滞剂预防应激性溃疡对接受有创机械通气的 ICU 患者院内死亡率的影响

重要性 质子泵抑制剂 (PPI) 或组胺 2 受体阻滞剂 (H2RB) 通常在重症监护病房 (ICU) 中作为应激性溃疡预防药物为患者开具处方。这些药物对死亡率的比较影响尚不清楚。目的比较使用 PPI 和 H2RB 预防应激性溃疡的院内死亡率。设计、设置和参与者 集群交叉随机临床试验于 2016 年 8 月至 2019 年 1 月在 5 个国家的 50 个 ICU 进行。需要在 ICU 入住 24 小时内进行有创机械通气的患者在医院进行了 90 天的随访。干预 比较了两种应激性溃疡预防策略（优先使用 PPI 与优先使用 H2RB）。每个ICU以随机顺序连续使用每种策略6个月；25 名 ICU 被随机分配到使用 PPI 然后使用 H2RB 的顺序，25 间 ICU 被随机分配到使用 H2RB 然后使用 PPI 的顺序（13 436 名患者按站点随机分配到 PPI，13 392 名按站点随机分配到 H2RB ）。主要结果和措施 主要结果是住院期间 90 天内的全因死亡率。次要结果是具有临床意义的上消化道出血、艰难梭菌感染以及 ICU 和住院时间。结果 在随机分组的 26 982 名患者中，154 名选择退出，26 828 名接受分析（平均 [SD] 年龄，58 [17.0] 岁；9691 [36.1%] 名女性）。有 26 771 名患者（99.2%）被纳入死亡率分析；到第 90 天，PPI 组 13 415 名患者中有 2459 名 (18.3%) 在医院死亡，13 356 名患者中有 2333 名 (17. 5%) H2RB 组在第 90 天在医院死亡（风险比，1.05 [95% CI，1.00 至 1.10]；绝对风险差，0.93 个百分点 [95% CI，-0.01 至 1.88] 个百分点；P = .054）。估计有 4.1% 按 ICU 地点随机分配至 PPI 的患者实际接受了 H2RB，估计有 20.1% 按 ICU 地点随机分配至 H2RB 的患者实际接受了 PPI。PPI 组和 H2RB 组分别有 1.3% 和 1.8% 的患者发生了具有临床意义的上消化道出血（风险比，0.73 [95% CI，0.57 至 0.92]；绝对风险差异，-0.51 个百分点 [95% CI，-0.90]至 -0.12 个百分点]；P = .009）。艰难梭菌感染率、ICU 和住院时间在治疗组之间没有显着差异。PPI 组的 1 名患者报告了一项不良事件（过敏反应）。结论和相关性 在需要机械通气的 ICU 患者中，使用质子泵抑制剂和组胺 2 受体阻滞剂预防应激性溃疡的策略分别导致医院死亡率为 18.3% 和 17.5%，差异未达到显着性临界点。然而，研究解释可能会因使用指定药物的交叉而受到限制。试验注册 anzctr.org.au 标识符：ACTRN12616000481471。研究解释可能会因使用指定药物的交叉而受到限制。试用注册 anzctr.org.au 标识符：ACTRN12616000481471。研究解释可能会因使用指定药物的交叉而受到限制。试验注册 anzctr.org.au 标识符：ACTRN12616000481471。