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RecruitingInterventionalPhase 2

MAGIC-AKI: Magnesium for the Prevention of Hyperthermic Intraoperative Cisplatin-Associated AKI

NCT ID: NCT05730816Sponsor: Brigham and Women's HospitalLast updated: 2025-11-21

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 1\. • Adult patients (≥18 years old) with malignant mesothelioma undergoing surgery with HIOC with Dr. Raphael Bueno or another BWH thoracic surgeon Exclusion Criteria: 1. 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). 2. Serum Mg \>3 mg/dl on either screening labs or preoperative labs 3. Pregnant/breastfeeding 4. Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy, myositis) 5. 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 6. Sinus bradycardia, defined as a heart rate (HR) \<55 beats per minute (bpm) detected on any ECG in the preceding 6 months 7. High grade AV block (2nd degree AV block type II or 3rd degree AV block) without a pacemaker 8. Positive COVID test in the 10 days prior to surgery 9. Prisoner 10. Hypersensitivity to Mg sulfate 11. Concurrent participation in a study with an alternative experimental therapy that may interact with IV Mg 12. Any condition that, in the view of the PI, might place the patient at increased risk or compromise the integrity of the study 13. Conflict with other study

Study locations (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02130

Recruiting
Shruti Gupta · Contact
David E. Leaf · Contact