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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Coronary Artery Disease, Coronary Artery Angiography, Coronary Catheterization, Contrast-induced Nephropathy, Stable Angina, Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Vitamin E
* Drug: N-acetyl cysteine
* Drug: Placebo oral capsule
* Drug: Placebos
* Drug: Normal Saline Flush, 0.9% Injectable Solution


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* The placebo of vitamin E as a soft gel capsule with the consumption order similar to vitamin e group<br>Drug: Placebos<br>* The placebo of n-acetylcysteine as a tablet with the consumption order similar to n-acetylcysteine group<br>Drug: Normal Saline Flush, 0.9% Injectable Solution<br>* Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization<br>|
| Active Comparator: Vitamin E<br>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: Vitamin E<br>* As a gel capsule of vitamin E 800 IU orally 2 hours before intervention and 400 IU orally 4 hours after intervention<br>Drug: Placebos<br>* The placebo of n-acetylcysteine as a tablet with the consumption order similar to n-acetylcysteine group<br>Drug: Normal Saline Flush, 0.9% Injectable Solution<br>* Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization<br>|
| Active Comparator: NAC<br>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: N-acetyl cysteine<br>* As an effervescent tablets of NAC 1200 mg orally 2 hours before intervention and 1200 mg orally 4 hours after intervention<br>Drug: Placebo oral capsule<br>* The placebo of vitamin E as a soft gel capsule with the consumption order similar to vitamin e group<br>Drug: Normal Saline Flush, 0.9% Injectable Solution<br>* Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization<br>|

What is the study measuring?
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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 |