The Effect of Curcumin Against Colistin-induced Nephrotoxicity

Study Overview
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Brief Summary
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The goal of this study is to investigate the possible nephroprotective effect of curcumin in critically ill patients receiving colistin.

Detailed Description
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The study will investigate the possible nephroprotective effect of curcumin when added to patients infected by MDR Gram-negative bacteria and require intravenous colistin therapy, curcumin will be given concurrently with colistin and discontinued at the same time as Colistin.

Official Title
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The Effect of Curcumin Against Colistin-induced Nephrotoxicity

Conditions
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Acute Kidney Injury, Drug-Induced Nephropathy

Intervention / Treatment
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* Drug: Colistin
* Drug: Curcumin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All critically ill adult patients (18-65 years old) who are infected by MDR Gram-negative bacteria and require intravenous colistin therapy Exclusion Criteria: Patients receiving intravenous colistin therapy for < 72 hours. Patients receiving renal replacement therapy (RRT). Patients with diseases that may contribute to renal impairment such as systemic lupus erythematosus, acute myocardial infarction, cancer, HIV infection, glucose-6-phosphate-dehydrogenase deficiency, or urinary tract stone. Pregnancy or breastfeeding. Known allergy to the study medications. Patients with chronic kidney diseases (creatinine clearance < 60 mg/dL). Elevated total liver enzymes (AST, and ALT) three times above the upper limit of normal. Patients with acute decompensated heart failure signs and symptoms requiring intravenous loop diuretics and/or intravenous inotropes and/or ACE inhibitors. Uncontrolled diabetes (Glycosylated hemoglobin (Hb A1C) >8%). Hypotensive patients defined as decrease in blood pressure less than 90/60 mm Hg. Recent use of vitamins with antioxidant properties such as beta carotene, vitamin E, vitamin C, selenium, or N-acetylcysteine or any other medications known to have nephroprotective activities. Patients receiving other nephrotoxic drugs at enrollment (e.g., aminoglycosides, vancomycin, or amphotericin B) or administration of contrast medium within 7 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>patients in this group will receive loading dose of colistin intravenously of 9 MIU followed by maintenance doses of 4.5 MIU given every 12 hours. | Drug: Colistin<br>* added for infection with multi drug resistant bacteria<br>|
| Active Comparator: Group 2<br>patients in this group will receive loading dose of colistin intravenously of 9 MIU followed by maintenance doses of 4.5 MIU given every 12 hours and curcumin will be administered as orally or through nasogastric tube at a dose of 2 capsules every 6 hours (1 gm/6 hour) | Drug: Colistin<br>* added for infection with multi drug resistant bacteria<br>Drug: Curcumin<br>* added for the possible nephroprotective effect<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of acute kidney injury | colistin induced nephrotoxicity (CIN) is defined as increase of serum creatinine by 0.3 mg/dL 48 hours after colistin administration | Baseline to hospital discharge, an average of 14 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of acute tubular necrosis (ATN) | will be evaluated by fractional excreted sodium (FENa) | Baseline to hospital discharge, an average of 14 days. | 
| The difference between the levels of urinary NGAL |  | Baseline to hospital discharge, an average of 14 days. | 
| Mortality rate |  | Baseline to 30 days post discharge | 
| Total length of ICU and hospital stays. |  | Baseline to hospital discharge, an average of 14 days. |