MAGIC-AKI: Magnesium for the Prevention of Hyperthermic Intraoperative Cisplatin-Associated AKI
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- AUC of SCr measured daily over 7 days in Mg- versus placebo-treated patients
研究概览
简要总结
In this research study, investigators will test whether prophylactic high-dose IV Mg administration attenuates the risk of AKI in patients with malignant mesothelioma receiving intraoperative chemotherapy (HIOC) with cisplatin compared to placebo
.
详细描述
In this phase 2, open-label randomized, placebo-controlled trial, investigators will test whether prophylactic high-dose IV Mg administration attenuates the risk of HIOC-associated AKI in patients with malignant mesothelioma undergoing surgery with HIOCC. Investigators will randomly assign 130 patients to receive IV Mg versus an equal volume of normal saline (0.9% NS) placebo, of whom it is anticipated 80 will complete the study. Investigators will also collect blood and urine pre- and postoperatively for exploration of secondary outcomes.
Investigators will screen for eligibility at participant's preoperative visit with their thoracic surgeon. Intravenous magnesium will be administered as a continuous infusion, soon after induction and stabilization by anesthesia in the operating room. The magnesium drip will start at 1 g/hour and will be titrated to achieve target levels of 3-5 mg/dl. The total duration of the infusion will be 24 hours.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. • Adult patients (≥18 years old) with malignant mesothelioma undergoing surgery with HIOC with Dr. Raphael Bueno or another BWH thoracic surgeon
排除标准
- •eGFR<45 ml/min/1.73m2 on either screening labs or preoperative labs, or end-stage kidney disease receiving renal replacement therapy. Screening labs refer to those obtained at the preoperative visit with the surgeon or within 90 days prior, whereas preoperative labs are obtained on the day of admission (typically one to three days priors to surgery).
- •Serum Mg >3 mg/dl on either screening labs or preoperative labs
- •Pregnant/breastfeeding
- •Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy, myositis)
- •Coronary artery disease, defined as any of the following in the prior year: a positive stress test; coronary angiogram indicating 1 or more vessels with >70% stenosis; percutaneous coronary intervention with stents; or coronary artery bypass graft surgery
- •Sinus bradycardia, defined as a heart rate (HR) <55 beats per minute (bpm) detected on any ECG in the preceding 6 months
- •High grade AV block (2nd degree AV block type II or 3rd degree AV block) without a pacemaker
- •Positive COVID test in the 10 days prior to surgery
- •Hypersensitivity to Mg sulfate
- •Concurrent participation in a study with an alternative experimental therapy that may interact with IV Mg
- •Any condition that, in the view of the PI, might place the patient at increased risk or compromise the integrity of the study
- •Conflict with other study
研究组 & 干预措施
Magnesium Sulfate
The IV Mg will start at 1 g/hour (25 ml/hour) within one hour following induction of anesthesia and stabilization of the patient. The infusion will continue for 24 hours and serum Mg levels will be monitored every 4 hours (+/-1 hour) for 28 hours following initiation of the Mg. Dose adjustments to the Mg infusion will be made as necessary to reach target serum Mg levels (3-5 mg/dl).
干预措施: Magnesium sulfate (Drug)
Normal Saline
Patients randomized to placebo will receive an equal volume of normal saline (0.9% NS) placebo which will be administered as a continuous infusion at 25 ml/hour. The infusion will continue for 24 hours.
干预措施: Normal Saline (Drug)
结局指标
主要结局
AUC of SCr measured daily over 7 days in Mg- versus placebo-treated patients
时间窗: 7 days
The primary endpoint is the area under the curve (AUC) of SCr measured daily over 7 days in Mg- versus placebo-treated patients
Composite Global Rank
时间窗: 7 days
As a secondary endpoint, investigators will construct a composite global rank endpoint in which the highest rank is assigned to those who die within 7 days, the second highest rank is assigned to those who survive but require RRT within 7 days, and all others ranked according to their SCr AUC, since RRT and death are important competing risks.
次要结局
- Renal tubular injury(2 days)
- Composite outcome of RRT/in-hospital death(7 days)
- Myocardial injury(7 days)
- Incident AKI(7 days)
- Maximum AKI stage(7 days)
- Vasoactive-inotropic score (VIS)(2 days)
- Proportion of patients with serum Mg levels in the 3-5 mg/dl range in the treatment group(1 day)
- New onset of atrial fibrillation(7 days)
- AUC for platinum concentrations(2 days)
研究者
Shruti Gupta
Director of Onconephrology
Brigham and Women's Hospital