The Effect of Curcumin Against Colistin-induced Nephrotoxicity

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

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Drug-Induced Nephropathy
• Intervention / Treatment: Drug: Colistin; Drug: Curcumin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 214
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alaa M. Hammad; Phone Number: 01000675555; Email: alaa.hammad.ph@o6u.edu.eg

Study Locations

• Egypt
  • Cairo, Egypt, 1133
    • Recruiting
    • Cairo University Hospitals
    • Contact: Alaa M Hammad; Phone Number: 01000675555; Email: alaa.hammad.ph@o6u.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 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; added for infection with multi drug resistant bacteria
Active Comparator: Group 2; 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; added for infection with multi drug resistant bacteria; Drug: Curcumin; added for the possible nephroprotective effect

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: October 6 University
• Collaborators: Cairo University
• Investigators: Principal Investigator: Nirmeen A. Sabry, Professor of Clinical Pharmacy Faculty of Pharmacy Cairo University; Principal Investigator: Maggie M. Abbassi, Professor of Clinical Pharmacy Faculty of Pharmacy Cairo University; Principal Investigator: Rania El-Husseiny, Professor of Critical Care Medicine, Faculty of Medicine Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): October 30, 2024

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 5, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Anti-Bacterial Agents; Colistin; Curcumin
• Other Study ID Numbers: curcumin in nephrotoxicity

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No