Prevention of Post-Cardiac Surgery Acute Kidney Injury by Proton Pump Inhibitor: A Prospective Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Kidney Injury Molecule-1 (KIM-1) Above Baseline Within 24 Hours Postoperatively
研究概览
简要总结
The purpose of this study is to determine whether perioperative intravenous administration of pantoprazole will improve kidney function parameters following cardiac surgery with cardiopulmonary bypass compared to famotidine and to determine whether perioperative intravenous administration of pantoprazole will decrease the incidence of postoperative Acte Kidney Injury (AKI) and major adverse kidney events (MAKE).
详细描述
Each year more than 500,000 cardiac surgeries are performed in the United States of America (USA) alone. Acute kidney injury (AKI) is a common complication following cardiac surgery and is associated with poor patient outcomes and increased healthcare costs. Therefore, there is an urgent need to identify medical interventions and treatments that prevent AKI or mitigate its severity when it occurs after cardiac surgery.
One of the main causes of AKI following cardiac surgery involves renal hypoperfusion/ischemia and reperfusion injury. Hypoxia-inducible factors (HIFs) are key transcription factors responsible for tissue adaptation to low oxygen, which orchestrate the expression of a wide variety of genes including a set of micro-ribonucleic acid (microRNAs). MicroRNAs are endogenous single-stranded noncoding miRNAs of nucleotides that participate in physiological and pathological functions via regulating post-transcription of target genes. During ischemic injury, hypoxia upregulates endothelial MicroRNAs that has the potential in renal protection through vascular integrity and regeneration. Additionally, microRNAs exert protective effects via decreasing apoptosis and promoting tubular cell proliferation during ischemic AKI.
Moreover, decreased serum levels of MicroRNAs are highly correlated with AKI severity in the intensive care unit (ICU) patients. Our preliminary study identified ATP4A as the downstream target gene of MicroRNAs in the kidney. Adenosine triphosphate (ATP)4A (catalytic α subunit of H+/K+ ATPase) is located in intercalated cells in the distal tubules and cortical collecting ducts, which regulates urine acidification through secretion of hydrogen and reabsorption of potassium from urine. Proton pump inhibitors (PPIs) block the ATP hydrolysis of the H+/K+ ATPase via binding its active site of ATP4A and further enhance this endogenous kidney protection pathway. Despite robust animal model data, randomized controlled trial aiming to test the effectiveness of PPI in post-cardiac surgery AKI prevention is lacking. If proven to be effective, our studies could be easily implemented in clinical practice and serve as an effective treatment for perioperative AKI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
The outcome assessor who tests the urinary kidney injury biomarkers is blinded.
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Scheduled for elective cardiac surgery with cardio pulmonary bypass (CPB) with a moderate to high risk of developing AKI (Cleveland risk score equal or higher than 3)
排除标准
- •Preoperative eGFR<30 ml/min per 1.73 m2
- •Dialysis dependence
- •Emergency surgery
- •Pregnancy
- •Nursing Patients
- •Interstitial nephritis
- •Proton pump inhibitors (PPIs) hypersensitivity
- •Liver disease
- •Vitamin B12 deficiency
研究组 & 干预措施
Pantoprazole
Pantoprazole (40 mg iv every 12 hours/q12H) for 2 days perioperatively [first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on postoperative (POD) 1 for a total of 4 doses over 2 days]. There will be no other modifications in patient care.
干预措施: Pantoprazole (Drug)
Famotidine
Famotidine (20 mg iv q12H) for 2 days perioperatively [first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days]. There will be no other modifications in patient care.
干预措施: Famotidine (Drug)
结局指标
主要结局
Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Kidney Injury Molecule-1 (KIM-1) Above Baseline Within 24 Hours Postoperatively
时间窗: from baseline (time 0) to 24 hours postoperatively
The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng\*h/mL).
次要结局
- Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Neutrophil Gelatinase-associated Lipocalin (NGAL) Above Baseline Within 24 Hours Postoperatively(from baseline (time 0) to 24 hours postoperatively)
- Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Tissue Inhibitor of Metalloproteinases 2 (TIMP-2) Above Baseline Within 24 Hours Postoperatively(from baseline (time 0) to 24 hours postoperatively)
- Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Insulin-like Growth Factor-binding Protein 7 (IGFBP-7) Above Baseline Within 24 Hours Postoperatively(from baseline (time 0) to 24 hours postoperatively)
- Number of Participants With Any-stage Postoperative Acute Kidney Injury (AKI)(from baseline to postoperative day 7 (or hospital discharge if earlier))
- Number of Participants With Major Adverse Kidney Events (MAKE)(from baseline to 30 days after surgery)
研究者
yafen liang
Professor
The University of Texas Health Science Center, Houston