MAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI
- Registration Number
- NCT05730816
- Lead Sponsor
- Brigham and Women's Hospital
- Brief Summary
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
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- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 130
- • Adult patients (≥18 years old) with malignant mesothelioma undergoing surgery with HIOC with Dr. Raphael Bueno or another BWH thoracic surgeon
- 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
- Prisoner
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Normal Saline 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. Magnesium Sulfate 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).
- Primary Outcome Measures
Name Time Method AUC of SCr measured daily over 7 days in Mg- versus placebo-treated patients 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 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.
- Secondary Outcome Measures
Name Time Method Renal tubular injury 2 days AUC of uNGAL, uKIM-1, and pKIM-1 at hours +4, +12, and +36 in relation to HIOC administration
Composite outcome of RRT/in-hospital death 7 days Composite outcome
Myocardial injury 7 days Defined as clinical evidence of myocardial injury and a troponin level above the 99th percentile
Incident AKI 7 days Urine output \<0.5 ml/kg/h x consecutive 6 hours in the first 48 hours following surgery with HIOC (this will only be assessed for the first 48 hours, as patients are transferred out of the ICU and/or their foley is removed, which prevents accurate hourly assessment of UOP); An absolute increase in SCr ≥0.3 mg/dl within 48 hours; C) A relative increase in SCr ≥50% compared to the baseline value in the first 7 days; D) Receipt of RRT in the first 7 days
Vasoactive-inotropic score (VIS) 2 days Assessed every 4 hours for the first 24 hours, and then every 8 hours for the next 24 hours, in relation to the start of the Mg infusion. The VIS is a validated method for integrating all vasoactive medications (i.e., vasopressors and inotropes) and their doses on an hourly basis into a single measure, and has been used in multiple settings
Proportion of patients with serum Mg levels in the 3-5 mg/dl range in the treatment group 1 day Between hours +8 and +24 in relation to the start of the Mg infusion
New onset of atrial fibrillation 7 days Confirmed on an EKG
AUC for platinum concentrations 2 days Using blood and urine collected at various time points
Maximum AKI stage 7 days Based on KDIGO staging
Trial Locations
- Locations (1)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States