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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cis-Platinum Nephropathy, Mannitol Adverse Reaction

Intervention / Treatment
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* Drug: Mannitol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who was at least 18 years old. Patients who had been diagnosed with cancer proven by tissue biopsy. 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. Patients were required to have a normal renal function (GFR > 60 mL/min/1.73m2). Patients with an Eastern Cooperative Oncology Group (ECOG) score ≤ 2. Patients with normal serum sodium and serum potassium level. Exclusion Criteria: Patients with any acute kidney injury event before randomized into trial not more than 6 months. Patients with chronic kidney disease or hydronephrosis. Patients with history of nephrectomy. Patients who had previously received immunosuppressants for any immune deficiency disease. Patients with who had received chemotherapy which induce nephrotoxicity. Patients with had received drug which is nephrotoxic (amphotericin B, aminoglycoside or non-steroidal anti-inflammatory drug). Patients who had cirrhosis with child pugh score more than 7. Patients with or had a known allergy to cisplatin or mannitol. Patients with chronic heart failure who cannot received fluid more than 1 liter. Patients who were not comfortable to follow up at clinic for long term outcome.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |