The Use of Inorganic Nitrate for the Prevention of Contrast-induced Nephropathy (NITRATE-CIN)

Barts & The London NHS Trust

Status and phase: Completed; Phase 2

Conditions: Acute Coronary Syndrome; Acute Kidney Injury; Contrast-induced Nephropathy

Treatments: Drug: Potassium Nitrate; Drug: Potassium Chloride

Study type: Interventional

Funder types: Other

Identifiers

NCT03627130

18/1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 640 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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640 participants in 2 patient groups, including a placebo group

Potassium Nitrate

Active Comparator group

Description:

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

Treatment:

Drug: Potassium Nitrate

Potassium Chloride

Placebo Comparator group

Description:

Potassium Chloride

Treatment:

Drug: Potassium Chloride