PDF(Pubmed)
Abstract：
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown.
To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction.
Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023.
Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first.
The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models.
Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group.
The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin.
ClinicalTrials.gov Identifier: NCT05558098.
To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction.
Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023.
Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first.
The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models.
Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group.
The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin.
ClinicalTrials.gov Identifier: NCT05558098.
摘要：
■钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂可改善2型糖尿病患者的预后，心力衰竭,和慢性肾病，但它们对器官衰竭危重患者预后的影响尚不清楚.
■要确定是否添加达格列净，SGLT-2抑制剂，标准重症监护病房(ICU)治疗可改善急性器官功能障碍危重患者的预后.
■多中心，随机化，开放标签，在巴西22个ICU进行的临床试验。计划外ICU入院并表现为至少1个器官功能障碍（呼吸，心血管,或肾脏）在2022年11月22日至2023年8月30日之间纳入，随访至2023年9月27日。
■参与者被随机分配10毫克达格列净(干预，n=248)加标准护理或仅标准护理(对照，n=259）长达14天或直到ICU出院，以先发生者为准。
■主要结局是医院死亡率的分层综合，开始肾脏替代疗法，ICU的住院时间为28天，使用获胜比率法进行分析。次要结果包括分层结果的各个组成部分，无器官支持日的持续时间，ICU,住院，使用贝叶斯回归模型进行评估。
■在507名随机参与者中(平均年龄，63.9[SD,15]年；46.9%，women),39.6％的人因怀疑感染而入院ICU。从ICU入院到随机分组的中位时间为1天(IQR，0-1）。达格列净对主要结局的胜率为1.01（95％CI，0.90至1.13；P=.89）。在所有次要结果中，在dapagliflozin组的27例患者(10.9%)和对照组的39例患者(15.1%)中,dapagliflozin使用肾脏替代治疗的获益概率最高为0.90.
■在危重患者和急性器官功能障碍的标准治疗中添加达格列净并没有改善临床结果；然而，置信区间较宽,不能排除达格列净的相关益处或危害.
■ClinicalTrials.gov标识符：NCT05558098。
■要确定是否添加达格列净，SGLT-2抑制剂，标准重症监护病房(ICU)治疗可改善急性器官功能障碍危重患者的预后.
■多中心，随机化，开放标签，在巴西22个ICU进行的临床试验。计划外ICU入院并表现为至少1个器官功能障碍（呼吸，心血管,或肾脏）在2022年11月22日至2023年8月30日之间纳入，随访至2023年9月27日。
■参与者被随机分配10毫克达格列净(干预，n=248)加标准护理或仅标准护理(对照，n=259）长达14天或直到ICU出院，以先发生者为准。
■主要结局是医院死亡率的分层综合，开始肾脏替代疗法，ICU的住院时间为28天，使用获胜比率法进行分析。次要结果包括分层结果的各个组成部分，无器官支持日的持续时间，ICU,住院，使用贝叶斯回归模型进行评估。
■在507名随机参与者中(平均年龄，63.9[SD,15]年；46.9%，women),39.6％的人因怀疑感染而入院ICU。从ICU入院到随机分组的中位时间为1天(IQR，0-1）。达格列净对主要结局的胜率为1.01（95％CI，0.90至1.13；P=.89）。在所有次要结果中，在dapagliflozin组的27例患者(10.9%)和对照组的39例患者(15.1%)中,dapagliflozin使用肾脏替代治疗的获益概率最高为0.90.
■在危重患者和急性器官功能障碍的标准治疗中添加达格列净并没有改善临床结果；然而，置信区间较宽,不能排除达格列净的相关益处或危害.
■ClinicalTrials.gov标识符：NCT05558098。
