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 .
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
130
Intravenous infusion of magnesium sulfate prior to intraoperative chemotherapy with cisplatin.
Intravenous infusion of normal saline.
Brigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGAUC of SCr measured daily over 7 days in Mg- versus placebo-treated patients
The primary endpoint is the area under the curve (AUC) of SCr measured daily over 7 days in Mg- versus placebo-treated patients
Time frame: 7 days
Composite Global Rank
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.
Time frame: 7 days
Incident AKI
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
Time frame: 7 days
Composite outcome of RRT/in-hospital death
Composite outcome
Time frame: 7 days
Maximum AKI stage
Based on KDIGO staging
Time frame: 7 days
Renal tubular injury
AUC of uNGAL, uKIM-1, and pKIM-1 at hours +4, +12, and +36 in relation to HIOC administration
Time frame: 2 days
AUC for platinum concentrations
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Using blood and urine collected at various time points
Time frame: 2 days
Vasoactive-inotropic score (VIS)
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
Time frame: 2 days
Proportion of patients with serum Mg levels in the 3-5 mg/dl range in the treatment group
Between hours +8 and +24 in relation to the start of the Mg infusion
Time frame: 1 day
New onset of atrial fibrillation
Confirmed on an EKG
Time frame: 7 days
Myocardial injury
Defined as clinical evidence of myocardial injury and a troponin level above the 99th percentile
Time frame: 7 days