Atorvastatin Versus Rosuvastatin on Contrast Induced Acute Kidney Injury (PRATO-ACS 2) (PRATO-ACS-2)

Impact of Early High-dose Atorvastatin Versus Rosuvastatin on Contrast Induced Acute Kidney Injury in Unselected Patients With Non- ST Elevation Acute Coronary Syndromes Scheduled for Early Invasive Strategy.

The aim of the project is to compare the nephro-protective effects of high-dose atorvastatin and high-dose rosuvastatin on the incidence of Contrast Induced-Acute Kidney Injury in patients with non-ST-elevation acute coronary syndromes scheduled for early invasive strategy.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Atorvastatin

Detailed Description

This is a prospective, single-centre, randomized study, designed to compare the nephro-protective effects of high-dose atorvastatin and high-dose rosuvastatin on the incidence of Contrast Induced-Acute Kidney Injury (CI-AKI). Consecutive statin-naïve patients admitted in the investigators institution for non-ST elevation Acute Coronary Syndrome (NSTE-ACS) and scheduled for early invasive strategy will be eligible.

Patients are randomized into two groups: 1) high-dose rosuvastatin (40 mg on-admission followed by 20 mg/day); 2) high-dose atorvastatin (80 mg on-admission followed by 40 mg/day). Randomization will be performed on-admission by computerized open-label assignment in blinded envelopes used in a consecutive fashion. All patients receive the standard pre-procedural hydration. The primary end-point is the proportion of patients with an increase in serum creatinine of ≥ 0.5 mg/dl or ≥ 25% above baseline within 72 hours after contrast medium administration. The secondary end-points are persistent worsening of renal damage (eGFR reduction >= 25% at 30 days) and cumulative adverse clinical events at follow-up. Specifically: death, myocardial infarction, dialysis, stroke or persistent renal damage at 30 days; death or myocardial infarction at 6 and 12 months.

• Study Type: Interventional
• Enrollment (Actual): 760
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Prato, Italy, 59100
    • Cardiology Division, Prato Hospital

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:

• All consecutive statin-naive patients with non ST-elevation acute coronary syndrome admitted to our institution and scheduled for early invasive strategy are considered for enrollment

Exclusion Criteria:

• Current statin treatment
• High-risk features warranting emergency coronary angiography (within 2 hours)
• Acute renal failure or end-stage renal failure requiring dialysis or serum creatinine ≥ 3 mg/dl
• Severe comorbidities which precluded early invasive strategy
• Contraindications to statin treatment
• Contrast media administration within the last 10 days
• Pregnancy
• Refusal of consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rosuvastatin; Rosuvastatin (40 mg on-admission followed by 20 mg/day) until discharge; then 20 mg/day (10 mg/day if creatinine clearance < 30 ml/min)	Drug: Rosuvastatin
Active Comparator: Atorvastatin; atorvastatin (80 mg on-admission followed by 40 mg/day before and after discharge)	Drug: Atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contrast Induced-Acute Kidney Injury	Increase in serum creatinine ≥ 0.5 mg/dl or ≥ 25 % within 72 hours of contrast medium exposure	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function at 30 days	Estimation of the glomerular filtration rate in all patients at 30 days	30 days after discharge
Cardiovascular and renal outcome	Composite cardiovascular and renal events at follow-up including acute renal failure requiring dialysis, persistent renal damage, all-causes mortality, myocardial infarction or stroke.	30 days, 6 months, 12 months
Anti-inflammatory effect of rosuvastatin and atorvastatin	High-sensitivity C-reactive protein (hs-CRP)will be measured on admission, at discharge and at 30 days.	On admission (baseline), at discharge (after 5 days) & at 30 days
Lipid-modulatory effects of atorvastatin and rosuvastatin	Low density lipoprotein (LDL) levels will be determined on admission, at discharge and at 30 days.	On admission (baseline), at discharge (after 5 days) & at 30 days
Myocardial Damage	Total cardiac biomarkers release during the index event	During hospitalization (average 5 days)

Collaborators and Investigators

• Sponsor: Centro Cardiopatici Toscani
• Investigators: Principal Investigator: Anna Toso, MD, Prato Hospital, Italy

Publications and helpful links

General Publications

• Toso A, Leoncini M, Maioli M, Tropeano F, Villani S, Bellandi F. A Prospective, Randomized, Open-Label Trial of Atorvastatin versus Rosuvastatin in the Prevention of Contrast-Induced Acute Kidney Injury, Worsened Renal Function at 30 Days, and Clinical Events After Acute Coronary Angiography: the PRATO-ACS-2 Study. Cardiorenal Med. 2020;10(5):288-301. doi: 10.1159/000506857. Epub 2020 May 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: May 30, 2013
• First Submitted That Met QC Criteria: June 5, 2013
• First Posted (Estimate): June 6, 2013

Study Record Updates

• Last Update Posted (Estimate): October 6, 2016
• Last Update Submitted That Met QC Criteria: October 5, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Statins; Contrast-Induced Acute Kidney Injury; Periprocedural Myocardial Damage
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Disease; Renal Insufficiency; Syndrome; Acute Kidney Injury; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium
• Other Study ID Numbers: 472013