Effects of DPP4 Inhibitor on Cisplatin Induced Acute Kidney Injury

Seoul National University Bundang Hospital182 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

182

Conditions

Cancer Cisplatin Adverse Reaction

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: up to 7 days

Secondary Outcomes

delta Cr

Change of serum creatinine from baseline to 7 days after cisplatin treatment.

Time frame: 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.