Vitamin E and N-acetylcysteine for Preventing Contrast-Induced Acute Kidney Injury After Coronary Artery Catheterization

Antioxidants for Preventing Contrast-Induced Acute Kidney Injury After Coronary Artery Catheterization

In a double-blinded randomized clinical trial, all patients undergoing coronary artery catheterization who will met our criteria, will be enrolled into three groups to receive either, vitamin e, n-acetylcysteine, or placebo. The aim of study will be to compare the superiority of vitamin e over n-acetylcysteine for the prevention of contrast-induced acute kidney injury (CIAKI).

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Acute Coronary Syndrome; Stable Angina; Contrast-induced Nephropathy; Coronary Catheterization; Coronary Artery Angiography
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: Placebos; Drug: Normal Saline Flush, 0.9% Injectable Solution; Drug: Vitamin E; Drug: N-acetyl cysteine

Detailed Description

Patients aged ≥18 years with chronic kidney disease who undergo coronary catheterization will be enrolled into the study if they meet the inclusion criteria. Patients will be randomly assigned into three groups in a 1:1:1 ratio (Computer-generated random number will be used to assign a patient in either group): we will use simple randomization for assigning each patient in a group. The participants, physicians and outcome assessors will be blinded throughout the trial until the opening of the randomization cold.

All patients will be entered into three group and they will be given normal saline 0.9%, vitamin E, NAC, and the placebos of both regimens. The vitamin E will be given as a soft gel capsule and its placebo will have the same shape and taste. The NAC will be given as an effervescent tablet with a glass of water for consumption and its placebo will also have the same shape and taste. These drugs will be given in addition to the routine hydration therapy which will be given to all patients.

Primary outcome will be the development of CIAKI. Secondary outcomes will be the development of major adverse cardiovascular events and any events till evaluating the CIAKI within 48-72 hours after intervention.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1995614331
    • Recruiting
    • Rajaie Cardiovascular Medical and Research Center
    • Contact: Majid Maleki, MD; Phone Number: 2043 +98 21 2392; Email: research@rhc.ac.ir

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Patients aged ≥18 years with baseline estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 (based on the Modification of Diet in Renal Disease study group formula) who undergo coronary catheterization (i.e. coronary angiography and percutaneous coronary intervention [PCI]) will be invited to the study if they meet the inclusion criteria: stable angina with ischemia and indication for coronary angiography, non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) requiring an early invasive strategy, and patients undergoing elective PCI .

Exclusion Criteria:

acute ST-segment elevation myocardial infarction, high-risk NSTE-ACS warranting emergency coronary angiography (<2 hours), cardiogenic shock, pulmonary edema, overt heart failure and/or ejection fraction <30%, ACS undergoing coronary angiography or angioplasty during the previous 5 days, sensitivity to contrast medium, recent administration of contrast medium for any reason, AKI, history of dialysis, pregnancy, newly prescribed angiotensin converting enzyme inhibitors or angiotensin receptor blockers, bleeding and/or coagulopathy diseases, and consumption of nephrotoxic drugs, vitamin E, vitamin C, or N-acetylcysteine (NAC) at least 48 hours before intervention.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with the placebos of both vitamin E and NAC (i.e. the placebo of vitamin E as a soft gel capsule and the placebo of NAC as an effervescent tablets along with a glass of water with the same consumption order used in the groups 2 and 3, respectively).	Drug: Placebo oral capsule; The placebo of vitamin E as a soft gel capsule with the consumption order similar to vitamin e group; Drug: Placebos; The placebo of n-acetylcysteine as a tablet with the consumption order similar to n-acetylcysteine group; Drug: Normal Saline Flush, 0.9% Injectable Solution; Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization
Active Comparator: Vitamin E; Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with vitamin E 800 IU orally 2 hours before intervention and 400 IU orally 4 hours after intervention plus the placebo of NAC with a consumption order similar to group 3.	Drug: Placebos; The placebo of n-acetylcysteine as a tablet with the consumption order similar to n-acetylcysteine group; Drug: Normal Saline Flush, 0.9% Injectable Solution; Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization; Drug: Vitamin E; As a gel capsule of vitamin E 800 IU orally 2 hours before intervention and 400 IU orally 4 hours after intervention
Active Comparator: NAC; Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with NAC 1200 mg orally 2 hours before intervention and 1200 mg orally 4 hours after intervention plus the placebo of vitamin E with the consumption order similar to group 2.	Drug: Placebo oral capsule; The placebo of vitamin E as a soft gel capsule with the consumption order similar to vitamin e group; Drug: Normal Saline Flush, 0.9% Injectable Solution; Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization; Drug: N-acetyl cysteine; As an effervescent tablets of NAC 1200 mg orally 2 hours before intervention and 1200 mg orally 4 hours after intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contrast-induced acute kidney injury	Contrast-induced acute kidney injury defined as an absolute increase ≥0.5 mg/dL or a relative increase ≥25% over baseline serum creatinine concentration within 48-72 hours after administration of contrast media.	48 to 72 hours after coronary catheterization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the levels of serum creatinine	Changes in serum creatinine after coronary artery catheterization	48-72 hours post-procedure
eGFR within 48-72 hours after coronary catheterization	Changes in eGFR after coronary artery catheterization	48-72 hours post-procedure
Changes in complete blood cell count components from baseline to follow-up	Changes in complete blood cell count components after coronary artery catheterization	48-72 hours post-procedure
Length of hospital stay	Length of hospital stay	48-72 hours post-procedure
Requirement for renal replacement therapies	Requirement for renal replacement therapies, ie, any kind of dialysis or renal transplantation	48-72 hours post-procedure
Post-procedure acute coronary syndrome (ACS) events	Recurrent acute coronary syndrome after coronary artery catheterization	48-72 hours post-procedure
Post-procedure cerebrovascular events	Cerebrovascular events after coronary artery catheterization	48-72 hours post-procedure
In-hospital mortality	In-hospital mortality after coronary artery catheterization	48-72 hours post-procedure
Post-procedure atrial fibrillation	Atrial fibrillation after coronary artery catheterization	48-72 hours post-procedure
Post-procedure bleeding	Bleeding events after coronary artery catheterization	48-72 hours post-procedure
Pulmonary embolism	Pulmonary embolism after coronary artery catheterization	48-72 hours post-procedure
Re-intervention	Repeated coronary artery catheterization	48-72 hours post-procedure

Collaborators and Investigators

• Sponsor: Rajaie Cardiovascular Medical and Research Center

Publications and helpful links

General Publications

• Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad MH. Short-Term High-Dose Vitamin E to Prevent Contrast Medium-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease Undergoing Elective Coronary Angiography: A Randomized Placebo-Controlled Trial. J Am Heart Assoc. 2016 Mar 15;5(3):e002919. doi: 10.1161/JAHA.115.002919.
• Rezaei Y, Hemila H. Vitamins E and C May Differ in Their Effect on Contrast-Induced Acute Kidney Injury. Am J Kidney Dis. 2017 May;69(5):708-709. doi: 10.1053/j.ajkd.2016.12.022. Epub 2017 Mar 6. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: November 25, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2018
• Last Update Submitted That Met QC Criteria: November 29, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Kidney Diseases; Urologic Diseases; Pain; Neurologic Manifestations; Renal Insufficiency; Coronary Disease; Chest Pain; Angina Pectoris; Coronary Artery Disease; Acute Kidney Injury; Acute Coronary Syndrome; Angina, Stable; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Micronutrients; Respiratory System Agents; Vitamins; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Vitamin E; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: Intervention-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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