Clinical trial NCT03627130: The Use of Inorganic Nitrate for the Prevention of Contrast-induced Nephropathy
Official title: Effect of Inorganic Nitrate on Contrast-induced Nephropathy in Patients Undergoing Coronary Angiography/Percutaneous Coronary Intervention for Acute Coronary Syndrome (ACS): A Randomised Single-centre, Double-blind Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Contrast-induced Nephropathy
Acute Kidney Injury
Acute Coronary Syndrome
Keywords: Percutaneous Coronary Intervention
Nitric Oxide
Nitrite
Acute Kidney Injury
Acute Coronary Syndrome
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
First posted: 2018-08-13
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Contrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is an important 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 an effective intervention. Dietary inorganic nitrate therapy, which through its chemical reduction in the body delivers nitric oxide has shown promise in attenuating CIN, but its effectiveness in preserving long-term renal function is unknown.

Detailed description: The NITRATE-CIN trial is a single-centre, randomised double-blinded placebo-controlled trial, which plans to recruit, over a period of 2 years, 640 patients presenting with acute coronary syndromes (ACS) who are at risk of CIN.

Patients will be randomised to either dietary inorganic nitrate therapy or placebo.

The primary endpoint will be the development of CIN (KDIGO criteria). A key secondary endpoint will be whether nitrate therapy impacts upon persistent renal impairment over a 3-month follow-up period. Additional secondary endpoints include the measurement of serum renal biomarkers (e.g. neutrophil gelatinase-associated lipocalin) and urinary albumin at 6, 48 h and 3 months following administration of contrast.

Findings from NITRATE-CIN will potentially demonstrate that nitrate attenuates contrast-induced acute and chronic kidney injury and influence future clinical practice guidelines in at-risk patients undergoing coronary angiographic procedures.

Eligibility criteria: Inclusion Criteria:

1. Patients undergoing coronary angiography+/-Percutaneous Coronary Intervention (PCI) for NSTE-ACS
2. Requirement for CIN prophylaxis as per Barts Heart Centre Criteria for CIN prophylaxis:

   eGFR\<60ml/min OR 2 of the following: diabetes, liver failure (cirrhosis), age \> 70yr, exposure to contrast in last 7 days, heart failure (or LVEF\<40%), concomitant renally active drugs (ACEi, ARB, NSAIDs, aminoglycosides, diuretics)
3. Aged \>18
4. Patients able and willing to give their written informed consent.

Exclusion Criteria:

1. ST segment myocardial infarction undergoing Primary PCI.
2. Patients with eGFR\<30ml/min or on renal replacement therapy
3. Subjects presenting with cardiogenic shock (systolic blood pressure \<80 mmHg for \>30 minutes, or requiring inotropes or emergency intra aortic balloon pump for hypotension treatment) or cardiopulmonary resuscitation
4. Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
5. Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
6. Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject's unwillingness to comply with all study related procedures).
7. Severe acute infection
8. Pregnancy
9. Breast-feeding mothers.
10. Any Inclusion Criteria not met

Primary outcomes:
measure: Contrast Induced Nephropathy
timeFrame: 48-72 hours
Secondary outcomes:
measure: Demonstration of a persistent benefit of dietary inorganic nitrate against long-term renal impairment
timeFrame: 3 months
measure: Measurement of Circulating Nitrite and Nitrate levels
timeFrame: Baseline, and at 6 hours, 48 hours and 3 months following treatment.
measure: Major Adverse Cardiac Events
timeFrame: 3 and 12 months follow-up
measure: Cost effectiveness of dietary inorganic Nitrate
timeFrame: 1 year
measure: To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by urinary renal biomarkers
timeFrame: 4-6 hours
measure: To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by serum biomarkers
timeFrame: 4-6 hours
measure: To determine if dietary inorganic nitrate decreases rates of post-procedural Myocardial Infarction
timeFrame: 6-12 hrs
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Barts Heart Centre
Study officials:
affiliation: Queen Mary University of London
name: Amrita Ahluwalia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beirne AM, Mitchelmore O, Palma S, Andiapen M, Rathod KS, Hammond V, Bellin A, Cooper J, Wright P, Antoniou S, Yaqoob MM, Naci H, Mathur A, Ahluwalia A, Jones DA. 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. J Cardiovasc Pharmacol Ther. 2021 Jul;26(4):303-309. doi: 10.1177/1074248421000520. Epub 2021 Mar 25.