The Effect of Intravenous Mannitol Plus Saline on the Prevention of Cisplatin-induced Nephrotoxicity: A Randomized, Double-blind, Placebo Controlled Trial (MACIN)

This study include cancer patients who had received chemotherapy that include cisplatin. Patients were randomly assigned to either a mannitol 20 g intravenous single dose after cisplatin or a placebo (saline). The primary outcome was to compare acute kidney injury (AKI), which was defined as increase creatinine 0.3 mg/dl in 48 hours by KDIGO criteria using serum creatinine and 24 hour urine creatinine to calculated.

Study Overview

• Status: Completed
• Conditions: Cis-Platinum Nephropathy; Mannitol Adverse Reaction
• Intervention / Treatment: Drug: Mannitol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who was at least 18 years old.
2. Patients who had been diagnosed with cancer proven by tissue biopsy.
3. Patients who were scheduled to receive cisplatin or combination of cisplatin and other chemotherapy, which the dose of cisplatin was not exceeded 100 mg/m2.
4. Patients were required to have a normal renal function (GFR > 60 mL/min/1.73m2).
5. Patients with an Eastern Cooperative Oncology Group (ECOG) score ≤ 2.
6. Patients with normal serum sodium and serum potassium level.

Exclusion Criteria:

1. Patients with any acute kidney injury event before randomized into trial not more than 6 months.
2. Patients with chronic kidney disease or hydronephrosis.
3. Patients with history of nephrectomy.
4. Patients who had previously received immunosuppressants for any immune deficiency disease.
5. Patients with who had received chemotherapy which induce nephrotoxicity.
6. Patients with had received drug which is nephrotoxic (amphotericin B, aminoglycoside or non-steroidal anti-inflammatory drug).
7. Patients who had cirrhosis with child pugh score more than 7.
8. Patients with or had a known allergy to cisplatin or mannitol.
9. Patients with chronic heart failure who cannot received fluid more than 1 liter.
10. Patients who were not comfortable to follow up at clinic for long term outcome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention; mannitol 20 gram plus 0.9% normal saline 100 ml one hour after cisplatin	Drug: Mannitol; Mannitol 20 gram plus 0.9% normal saline 100 ml one hour after cisplatin
Placebo Comparator: placebo; 0.9% normal saline 100 ml one hour after cisplatin	Drug: Placebo; 0.9% normal saline 100 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Kidney Injury	Rate of patients with serum creatinine increase 0.3 mg/dl or ≥50% or urine output of <0.5 mL/kg/hour for >6 hours by AKIN criteria	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decline 24-hour urine creatinine clearance	Rate of patients with lower than 60 mL/min/1.73m2 of 24-hour urine creatinine clearance after receiving cisplatin	48 hours

Collaborators and Investigators

• Sponsor: Phramongkutklao College of Medicine and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): February 14, 2021

Study Registration Dates

• First Submitted: January 30, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): January 21, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: R023h/62

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No