The Use of Inorganic Nitrate for the Prevention of Contrast-induced Nephropathy

Acute Coronary Syndrome Clinical Trial

— NITRATE-CIN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03627130
• Other study ID #: 18/1
• Status: Completed
• Phase: Phase 2
• Start date: November 29, 2018
• Est. completion date: May 30, 2022

Study information

• Verified date: December 2022
• Source: Barts & The London NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 640
• Est. completion date: May 30, 2022
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Kidney Injury
• Contrast-induced Nephropathy
• Kidney Diseases
• Syndrome

Intervention

Drug:
• Potassium Nitrate
Potassium nitrate capsules (KNO3: 12 mmol giving 744 mg of nitrate) for 5 days
• Potassium Chloride
Potassium Chloride capsules for 5 days

Locations

Country	Name	City	State
United Kingdom	Barts Heart Centre	London

Sponsors (1)

Lead Sponsor	Collaborator
Barts & The London NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Contrast Induced Nephropathy	Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria	48-72 hours
Secondary	Demonstration of a persistent benefit of dietary inorganic nitrate against long-term renal impairment	Difference in real function as measured by eGFR (estimated glomerular filtration rate) at 3 months post-contrast exposure	3 months
Secondary	Measurement of Circulating Nitrite and Nitrate levels	Plasma Nitrite/Nitrate levels	Baseline, and at 6 hours, 48 hours and 3 months following treatment.
Secondary	Major Adverse Cardiac Events	Defined as death, non-fatal myocardial infarction, revascularisation, acute heart failure, non-fatal stroke	3 and 12 months follow-up
Secondary	Cost effectiveness of dietary inorganic Nitrate	Incremental Cost Effectiveness Ratio (ICER)	1 year
Secondary	To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by urinary renal biomarkers	Measurement of urinary IGFB7/TIMP-2	4-6 hours
Secondary	To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by serum biomarkers	Measurement of serum Neutrophil gelatinase-associated lipocalin (NGAL)	4-6 hours
Secondary	To determine if dietary inorganic nitrate decreases rates of post-procedural Myocardial Infarction	Definition as per Society for Cardiovascular Angiography and Interventions (SCAI)	6-12 hrs