NITRATE-CIN Study: Protocol of a Randomized (1:1) Single-Center, UK, Double-Blind Placebo-Controlled Trial Testing the Effect of Inorganic Nitrate on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography for Acute Coronary Syndromes.

Abstract

BACKGROUND:

Contrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is a significant cause of morbidity/mortality following coronary angiographic procedures in high-risk patients. Despite preventative measures intended to mitigate the risk of CIN, there remains a need for novel effective treatments. Evidence suggests that delivery of nitric oxide (NO) through chemical reduction of inorganic nitrate to NO may offer a novel therapeutic strategy to reduce CIN and thus preserve long term renal function.

DESIGN:

The NITRATE-CIN trial is a single-center, randomized, double-blind placebo-controlled trial, which plans to recruit 640 patients presenting with acute coronary syndromes (ACS) who are at risk of CIN. Patients will be randomized to either inorganic nitrate therapy (capsules containing 12 mmol KNO3) or placebo capsules containing potassium chloride (KCl) daily for 5 days. The primary endpoint is development of CIN using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A key secondary endpoint is renal function over a 3-month follow-up period. Additional secondary endpoints include serum renal biomarkers (e.g. neutrophil gelatinase-associated lipocalin) at 6 h, 48 h and 3 months following administration of contrast. Cost-effectiveness of inorganic nitrate therapy will also be evaluated.

SUMMARY:

This study is designed to investigate the hypothesis that inorganic nitrate treatment decreases the rate of CIN as part of semi-emergent coronary angiography for ACS. Inorganic nitrate is a simple and easy to administer intervention that may prove useful in prevention of CIN in at-risk patients undergoing coronary angiographic procedures.

• Authors: Anne-Marie Beirne, Oliver Mitchelmore, Susana Palma, Mervyn Andiapen, Krishnaraj S Rathod, Victoria Hammond, Anna Bellin, Jackie Cooper, Paul Wright, Sotiris Antoniou, Muhammad Magdi Yaqoob, Huseyin Naci, Anthony Mathur, Amrita Ahluwalia, Daniel A Jones
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 26 Issue 4 Pg. 303-309 (07 2021) ISSN: 1940-4034 [Electronic] United States
• PMID: 33764198 (Publication Type: Clinical Trial Protocol, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Contrast Media
• Lipocalin-2
• Nitrates
• Potassium Compounds
• potassium nitrate

Topics

• Acute Coronary Syndrome (diagnostic imaging)
• Acute Kidney Injury (chemically induced, prevention & control)
• Contrast Media (adverse effects)
• Coronary Angiography (adverse effects, methods)
• Double-Blind Method
• Humans
• Kidney Function Tests
• Lipocalin-2 (blood)
• Nitrates (administration & dosage, adverse effects, economics)
• Potassium Compounds (administration & dosage, adverse effects, economics)
• Research Design
• United Kingdom