MAGIC-AKI: Magnesium for the Prevention of Hyperthermic Intraoperative Cisplatin-Associated AKI
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 .
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.
Arms & interventions
- DrugMagnesium sulfate
Intravenous infusion of magnesium sulfate prior to intraoperative chemotherapy with cisplatin.
- DrugNormal Saline
Intravenous infusion of normal saline.
Outcome measures
Primary
AUC 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
Secondary
Incident AKI
Time frame: 7 days
Composite outcome of RRT/in-hospital death
Time frame: 7 days
Maximum AKI stage
Time frame: 7 days
Renal tubular injury
Time frame: 2 days
AUC for platinum concentrations
Time frame: 2 days
Vasoactive-inotropic score (VIS)
Time frame: 2 days
Proportion of patients with serum Mg levels in the 3-5 mg/dl range in the treatment group
Time frame: 1 day
New onset of atrial fibrillation
Time frame: 7 days
Myocardial injury
Time frame: 7 days
Eligibility criteria
Study locations (1)
Brigham and Women's Hospital
Boston, Massachusetts, 02130