Curcuminoids and Contrast-induced Acute Kidney Injury

Curcuminoids Can Prevent Contrast-induced Acute Kidney Injury in Chronic Kidney Disease Patients Undergoing Elective Coronary Procedures: A Randomized Controlled Trial

The objective of this study was to evaluate the role of curcuminoids in the prevention of CI-AKI in CKD patients.The result of the study was prophylactic administration with curcuminoids in addition to standard treatment reduce the incidence of CI-AKI CKD patients undergoing elective CAG.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Acute Kidney Injury; Contrast Media Toxicity; Curcuminoid
• Intervention / Treatment: Drug: Curcuminoid; Drug: Placebo

Detailed Description

This study was a single-center, prospective, double-blinded, randomized placebo-controlled trial in CKD patients undergoing elective coronary angiography (CAG) at Vajira hospital from October 2018 to March 2019. Patients were stratified according to baseline estimate glomerular filtration rate (eGFR) and diabetes status. They were randomized to Curcuminoids 1,500 milligrams per day starting 3 days before and 2 days after coronary procedure or placebo. The primary outcome was the development of CI-AKI, defined as serum creatinine rising ≥ 0.3 mg/dL within 48 hours after coronary angiography. The secondary outcomes were overall AKI incidences within 7 days after CAG, changes in eGFR, IL-6 hs-CRP, and other adverse events.

A total of 60 patients were enrolled( 30 in curcuminoids group, and 30 in the control group). Overall AKI developed in 5 patients in control group and none in curcuminoids group (16.67% versus 0%, p-value 0.052). The results showed that curcuminoids could preserve changes in eGFR compared to the placebo group (-1.5 vs 2.5 mL/min/1.73m2, p-value <0.001 within 48 hours and -4 versus 1 mL/min/1.73m2, p-value 0.002 within 7 days). The high-sensitive C-reactive protein (hs-CRP) and IL-6 levels were not different between patients receiving curcuminoids and placebo. In curcuminoids group, 3 patients developed mild nausea and diarrhea that improved with supportive care. No serious adverse events were found in both groups.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10300
    • Navamindradhiraj University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All the patients undergoing elective CAG at Vajira hospital from October 2018 to March 2019 were included in the study
• older than 18 years old
• stable eGFR 15-60 mL/min/1.73m2 in last 3 months.

Exclusion Criteria:

• dialysis-dependent
• post-kidney transplantation
• acute heart failure or critically ill
• history of contrast or turmeric allergy
• increasing of alanine aminotransferase (ALT) or alkaline phosphatase (ALP) more than three times of normal upper limits or post-cholecystectomy
• history of AKI (as evidence by sCr change ≥ 0.3 mg/dL) within 14 days before the study - using medication included NSAIDs, warfarin, immunosuppression, N-acetyl cysteine, ascorbic acid or contrast agents within 14 days before the study
• pregnancy or lactation o
• denied consent .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Curcumioids; The investogators prescribed curcuminoids 1,500 mg/day . The regimen was curcuminoids 500 mg three times a day from three days before the procedure until two days after. All patients also received standard prophylaxis protocol which included 0.9% sodium chloride 1 mL/kg/hour, given 12 hours before and 12 hours after CAG unless contraindicated.	Drug: Curcuminoid; Patients were stratified according to baseline eGFR and diabetes status with 1:1 assignment into curcuminoids and placebo group. Curcuminoids (250 mg capsules) were purchased from the Government Pharmaceutical Organization of Thailand (Anti-ox® registration number 1A 1/60(H)), which contained curcumin: demethoxycurcumin: bis-demothoxycurcumin at the ratio of 1:0.5:0.2.
Placebo Comparator: Placebo; The placebo was identical capsule given three times daily and the remaining protocols were the same as the active group	Drug: Placebo; Identical capsules were used for the placebo from the same manufacturer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of AKI	the incidence of CI-AKI development between the addition of curcuminoids to standard protocol and standard protocol alone in patients who underwent CAG	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AKI of any cause within seven days after CAG	The incidence overallof AKI form any causes	7 days
Change in eGFR	The final eGFR compared to baseline eGFR before CAG	0,7 days
Change in IL-6 and hs-CRP	The final levels of inflammatory markers at the completion of study compare to baseline	0.7 days
Adverse events	The adverse events of curcuminoids	7 days

Collaborators and Investigators

• Sponsor: Bangkok Metropolitan Administration Medical College and Vajira Hospital

Publications and helpful links

General Publications

• Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. 2002 May;39(5):930-6. doi: 10.1053/ajkd.2002.32766.
• Mehran R, Dangas GD, Weisbord SD. Contrast-Associated Acute Kidney Injury. N Engl J Med. 2019 May 30;380(22):2146-2155. doi: 10.1056/NEJMra1805256. Review.
• Morcos R, Kucharik M, Bansal P, Al Taii H, Manam R, Casale J, Khalili H, Maini B. Contrast-Induced Acute Kidney Injury: Review and Practical Update. Clin Med Insights Cardiol. 2019 Nov 1;13:1179546819878680. doi: 10.1177/1179546819878680. eCollection 2019. Review.
• Kusirisin P, Chattipakorn SC, Chattipakorn N. Contrast-induced nephropathy and oxidative stress: mechanistic insights for better interventional approaches. J Transl Med. 2020 Oct 20;18(1):400. doi: 10.1186/s12967-020-02574-8. Review.
• Tasanarong A, Vohakiat A, Hutayanon P, Piyayotai D. New strategy of α- and γ-tocopherol to prevent contrast-induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures. Nephrol Dial Transplant. 2013 Feb;28(2):337-44. doi: 10.1093/ndt/gfs525. Epub 2013 Jan 12.
• Weisbord SD, Gallagher M, Jneid H, Garcia S, Cass A, Thwin SS, Conner TA, Chertow GM, Bhatt DL, Shunk K, Parikh CR, McFalls EO, Brophy M, Ferguson R, Wu H, Androsenko M, Myles J, Kaufman J, Palevsky PM; PRESERVE Trial Group. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018 Feb 15;378(7):603-614. doi: 10.1056/NEJMoa1710933. Epub 2017 Nov 12.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): March 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: May 13, 2021
• First Submitted That Met QC Criteria: May 13, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: coronary angiography; contrast-induced acute kidney injury; Curcuminoids
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: 157/61

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: After pub

Drug and device information, study documents

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