MAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI

Mesothelioma Clinical Trial

— MAGIC-AKI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05730816
• Other study ID #: 2023p000276
• Secondary ID: K23DK125672
• Status: Recruiting
• Phase: Phase 2
• Start date: April 4, 2023
• Est. completion date: January 1, 2028

Study information

• Verified date: April 2023
• Source: Brigham and Women's Hospital
• Contact: Shruti Gupta, MD, MPH
• Phone: 617-732-6383
• Email: Sgupta21[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

.

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 information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: January 1, 2028
• Est. primary completion date: April 3, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant

Intervention

Drug:
• Magnesium sulfate
Intravenous infusion of magnesium sulfate prior to intraoperative chemotherapy with cisplatin.
• Normal Saline
Intravenous infusion of normal saline.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	7 days
Primary	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.	7 days
Secondary	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	7 days
Secondary	Composite outcome of RRT/in-hospital death	Composite outcome	7 days
Secondary	Maximum AKI stage	Based on KDIGO staging	7 days
Secondary	Renal tubular injury	AUC of uNGAL, uKIM-1, and pKIM-1 at hours +4, +12, and +36 in relation to HIOC administration	2 days
Secondary	AUC for platinum concentrations	Using blood and urine collected at various time points	2 days
Secondary	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	2 days
Secondary	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	1 day
Secondary	New onset of atrial fibrillation	Confirmed on an EKG	7 days
Secondary	Myocardial injury	Defined as clinical evidence of myocardial injury and a troponin level above the 99th percentile	7 days