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

NCT03627130 | Completed Phase 2 DMC

• 1 other identifier: 18/1
• Study Type: interventional
• Target: 640
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Percutaneous Coronary Intervention; Nitric Oxide; Nitrite; Acute Kidney Injury; Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (1)

• Contrast Induced Nephropathy

  Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria

  48-72 hours

Secondary Outcomes (7)

• Demonstration of a persistent benefit of dietary inorganic nitrate against long-term renal impairment

  3 months

• Measurement of Circulating Nitrite and Nitrate levels

  Baseline, and at 6 hours, 48 hours and 3 months following treatment.

• Major Adverse Cardiac Events

  3 and 12 months follow-up

• Cost effectiveness of dietary inorganic Nitrate

  1 year

• To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by urinary renal biomarkers

  4-6 hours

Study Arms (2)

Potassium Nitrate

ACTIVE COMPARATOR

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

Drug: Potassium Nitrate

Potassium Chloride

PLACEBO COMPARATOR

Potassium Chloride

Drug: Potassium Chloride

Interventions

Potassium Nitrate DRUG

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

Potassium Nitrate

Potassium Chloride DRUG

Potassium Chloride capsules for 5 days

Potassium Chloride

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing coronary angiography+/-Percutaneous Coronary Intervention (PCI) for NSTE-ACS
• 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)
• Aged \>18
• Patients able and willing to give their written informed consent.

You may not qualify if:

• ST segment myocardial infarction undergoing Primary PCI.
• Patients with eGFR\<30ml/min or on renal replacement therapy
• 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
• Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
• 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.
• 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).
• Severe acute infection
• Pregnancy
• Breast-feeding mothers.

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

Barts Heart Centre

London, EC1A 7BE, United Kingdom

Location

Related Publications (2)

• Jones DA, Beirne AM, Kelham M, Wynne L, Andiapen M, Rathod KS, Parakaw T, Adams J, Learoyd A, Khan K, Godec T, Wright P, Antoniou S, Wragg A, Yaqoob M, Mathur A, Ahluwalia A. Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial. Eur Heart J. 2024 May 13;45(18):1647-1658. doi: 10.1093/eurheartj/ehae100.

  PMID: 38513060 DERIVED

• 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.

  PMID: 33764198 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury; Acute Coronary Syndrome

Interventions

potassium nitrate; Potassium Chloride

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Potassium Compounds

Study Officials

• Amrita Ahluwalia, PhD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: IMP and placebo will be identical
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2018
• First Posted: August 13, 2018
• Study Start: November 29, 2018
• Primary Completion: May 30, 2022
• Study Completion: May 30, 2022
• Last Updated: December 16, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Mid-late 2018
• Access Criteria: Freely available via journal

Locations

GB (1)