Clinical trial NCT05730816: MAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI
Official title: MAGIC-AKI: Magnesium for the Prevention of Hyperthermic Intraoperative Cisplatin-Associated AKI
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Mesothelioma
Keywords: Mesothelioma
Magnesium Sulfate
intraoperative cisplatin
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-02-16
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: AUC of SCr measured daily over 7 days in Mg- versus placebo-treated patients
timeFrame: 7 days
measure: Composite Global Rank
timeFrame: 7 days
Secondary outcomes:
measure: Incident AKI
timeFrame: 7 days
measure: Composite outcome of RRT/in-hospital death
timeFrame: 7 days
measure: Maximum AKI stage
timeFrame: 7 days
measure: Renal tubular injury
timeFrame: 2 days
measure: AUC for platinum concentrations
timeFrame: 2 days
measure: Vasoactive-inotropic score (VIS)
timeFrame: 2 days
measure: Proportion of patients with serum Mg levels in the 3-5 mg/dl range in the treatment group
timeFrame: 1 day
measure: New onset of atrial fibrillation
timeFrame: 7 days
measure: Myocardial injury
timeFrame: 7 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shruti Gupta, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: David E. Leaf, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References: