Effects of DPP4 Inhibitor on Cisplatin Induced Acute Kidney Injury

Study Overview
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Brief Summary
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Cisplatin is a potent chemotherapeutic agent, however, its nephrotoxicity manifested by acute kidney injury (AKI) often limits applicability. Dipeptidylpeptidase-4 (DPP4) inhibitors are well known to improve glucose intolerance by augmentation of endogenous glucagon like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP). DPP4 inhibitor also has the potential anti-apoptotic and renoprotective effect in a mouse model of cisplatin-induced AKI. This is a single-center, randomized, double-blind, parallel-group, placebo-controlled, prospective study to investigate the renoprotective effect of DPP4 inhibitor on cisplatin-induced AKI. A total 182 patients, who are scheduled to treat with cisplatin, will be recruited and randomly assigned to either Gemigliptin or placebo groups. Subjects will take study drugs for 8 days starting from one day before cisplatin treatment. Serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) will be measured at 7 days after cisplatin treatment.

Detailed Description
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This study will investigate possible renoprotective effects of DPP4 inhibitor on cisplatin induced acute kidney injury.

Official Title
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Effect of DPP4 Inhibitors on Cisplatin-induced Acute Kidney Injury

Conditions
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Cancer, Cisplatin Adverse Reaction

Intervention / Treatment
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* Drug: Gemigliptin
* Drug: Placebo
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 years cancer patients treated with intravenous cisplatin written consent Exclusion Criteria: Diabetes mellitus Chronic kidney disease stage IV-V (eGFR < 30ml/min/1.73m2) History of transplantation History of acute kidney injury before randomization Use of other nephrotoxic agents such as non steroidal anti-inflammatory drugs, aminoglycosides, colistin, vancomycin Receiving contrast media during last 72 hours Liver disease (bilirubin > 2 mg/dl, transaminase levels >2.5 times the upper limit normal) Active infection Patients with high risks of dehydration owing to poor oral intake High blood pressure (> 180/110 mmHg despite antihypertensive medications) Hypersensitivity to Gemigliptin or its excipients Low compliance to Gemigliptin treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental: Gemigliptin and Cisplatin<br>Gemigliptin 100mg daily in two divided doses for 8 days starting from one day before cisplatin-treatment | Drug: Gemigliptin<br>* Gemigliptin 100mg in 2 divided doses plus cisplatin<br>* Other names: Zemiglo;Drug: Cisplatin<br>* All patients will receive intravenous cisplatin<br>|
| Placebo Comparator: Control arm<br>Placebo 100mg daily in two divided doses for 8 days starting from one day before cisplatin-treatment | Drug: Placebo<br>* 100mg in 2 divided doses plus cisplatin<br>* Other names: Identical inert tablet to mimic gemigliptin (50mg);Drug: Cisplatin<br>* All patients will receive intravenous cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute kidney injury defined as any of the followings | Increase in sCr by ≥ 0.3 mg/dl Increase in sCr to ≥ 1.5 times baseline Decrease in eGFR to ≥ 25% All subjects receive Gemigliptin or placebo at a total dose of 100mg (50mg twice a day) for 8 consecutive days, serum creatinine will be measured. | up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delta Cr | Change of serum creatinine from baseline to 7 days after cisplatin treatment. | Time Frame: up to 7 days | 
| delta eGFR | Change of glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration equations (CKD EPI) from baseline to 7 days after cisplatin treatment. | up to 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cisplatin, Nephrotoxicity, Gemigliptin, DPP4 inhibitor