Back to resultsMAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI (MAGIC-AKI)
Primary Purpose
Mesothelioma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Magnesium sulfate
Normal Saline
Sponsored by
About this trial
This is an interventional prevention trial for Mesothelioma focused on measuring Mesothelioma, Magnesium Sulfate, intraoperative cisplatin
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: 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). Serum Mg >3 mg/dl on either screening labs or preoperative labs Pregnant/breastfeeding Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy, myositis) 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 Sinus bradycardia, defined as a heart rate (HR) <55 beats per minute (bpm) detected on any ECG in the preceding 6 months High grade AV block (2nd degree AV block type II or 3rd degree AV block) without a pacemaker Positive COVID test in the 10 days prior to surgery Prisoner Hypersensitivity to Mg sulfate Concurrent participation in a study with an alternative experimental therapy that may interact with IV Mg Any condition that, in the view of the PI, might place the patient at increased risk or compromise the integrity of the study Conflict with other study
Sites / Locations
- Brigham and Women's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Magnesium Sulfate
Normal Saline
Arm Description
The IV Mg will start at 1 g/hour (25 ml/hour) within one hour following induction of anesthesia and stabilization of the patient. The infusion will continue for 24 hours and serum Mg levels will be monitored every 4 hours (+/-1 hour) for 28 hours following initiation of the Mg. Dose adjustments to the Mg infusion will be made as necessary to reach target serum Mg levels (3-5 mg/dl).
Patients randomized to placebo will receive an equal volume of normal saline (0.9% NS) placebo which will be administered as a continuous infusion at 25 ml/hour. The infusion will continue for 24 hours.
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
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
Composite outcome of RRT/in-hospital death
Composite outcome
Maximum AKI stage
Based on KDIGO staging
Renal tubular injury
AUC of uNGAL, uKIM-1, and pKIM-1 at hours +4, +12, and +36 in relation to HIOC administration
AUC for platinum concentrations
Using blood and urine collected at various time points
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
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
New onset of atrial fibrillation
Confirmed on an EKG
Myocardial injury
Defined as clinical evidence of myocardial injury and a troponin level above the 99th percentile
Full Information
NCT ID
NCT05730816
First Posted
February 7, 2023
Last Updated
April 3, 2023
Sponsor
Brigham and Women's Hospital
Collaborators
National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT05730816
Brief Title
MAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI
Acronym
MAGIC-AKI
Official Title
MAGIC-AKI: Magnesium for the Prevention of Hyperthermic Intraoperative Cisplatin-Associated AKI
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 4, 2023 (Actual)
Primary Completion Date
April 3, 2027 (Anticipated)
Study Completion Date
January 1, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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
.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesothelioma
Keywords
Mesothelioma, Magnesium Sulfate, intraoperative cisplatin
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Magnesium Sulfate
Arm Type
Experimental
Arm Description
The IV Mg will start at 1 g/hour (25 ml/hour) within one hour following induction of anesthesia and stabilization of the patient. The infusion will continue for 24 hours and serum Mg levels will be monitored every 4 hours (+/-1 hour) for 28 hours following initiation of the Mg. Dose adjustments to the Mg infusion will be made as necessary to reach target serum Mg levels (3-5 mg/dl).
Arm Title
Normal Saline
Arm Type
Placebo Comparator
Arm Description
Patients randomized to placebo will receive an equal volume of normal saline (0.9% NS) placebo which will be administered as a continuous infusion at 25 ml/hour. The infusion will continue for 24 hours.
Intervention Type
Drug
Intervention Name(s)
Magnesium sulfate
Intervention Description
Intravenous infusion of magnesium sulfate prior to intraoperative chemotherapy with cisplatin.
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Intervention Description
Intravenous infusion of normal saline.
Primary Outcome Measure Information:
Title
AUC of SCr measured daily over 7 days in Mg- versus placebo-treated patients
Description
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
Title
Composite Global Rank
Description
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 Outcome Measure Information:
Title
Incident AKI
Description
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
Title
Composite outcome of RRT/in-hospital death
Description
Composite outcome
Time Frame
7 days
Title
Maximum AKI stage
Description
Based on KDIGO staging
Time Frame
7 days
Title
Renal tubular injury
Description
AUC of uNGAL, uKIM-1, and pKIM-1 at hours +4, +12, and +36 in relation to HIOC administration
Time Frame
2 days
Title
AUC for platinum concentrations
Description
Using blood and urine collected at various time points
Time Frame
2 days
Title
Vasoactive-inotropic score (VIS)
Description
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
Title
Proportion of patients with serum Mg levels in the 3-5 mg/dl range in the treatment group
Description
Between hours +8 and +24 in relation to the start of the Mg infusion
Time Frame
1 day
Title
New onset of atrial fibrillation
Description
Confirmed on an EKG
Time Frame
7 days
Title
Myocardial injury
Description
Defined as clinical evidence of myocardial injury and a troponin level above the 99th percentile
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
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).
Serum Mg >3 mg/dl on either screening labs or preoperative labs
Pregnant/breastfeeding
Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy, myositis)
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
Sinus bradycardia, defined as a heart rate (HR) <55 beats per minute (bpm) detected on any ECG in the preceding 6 months
High grade AV block (2nd degree AV block type II or 3rd degree AV block) without a pacemaker
Positive COVID test in the 10 days prior to surgery
Prisoner
Hypersensitivity to Mg sulfate
Concurrent participation in a study with an alternative experimental therapy that may interact with IV Mg
Any condition that, in the view of the PI, might place the patient at increased risk or compromise the integrity of the study
Conflict with other study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shruti Gupta, MD, MPH
Phone
617-732-6383
Email
Sgupta21@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shruti Gupta, MD, MPH
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David E. Leaf, MD, MMSc
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02130
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shruti Gupta
Email
sgupta21@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
David E. Leaf
Email
deleaf@bwh.harvard.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
IPD Sharing Time Frame
Data can be shared no earlier than 1 year following the date of publication
IPD Sharing Access Criteria
BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
Learn more about this trial
MAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI
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