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

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ClinicalTrials.gov Identifier: NCT03627130
Recruitment Status : Recruiting
First Posted : August 13, 2018
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Barts & The London NHS Trust

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.

Condition or disease Intervention/treatment Phase
Contrast-induced Nephropathy Acute Kidney Injury Acute Coronary Syndrome Drug: Potassium Nitrate Drug: Potassium Chloride Phase 2

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, 500 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 516 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: IMP and placebo will be identical
Primary Purpose: Treatment
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
Actual Study Start Date : November 29, 2018
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : October 1, 2021


Arm Intervention/treatment
Active Comparator: Potassium Nitrate
Potassium nitrate capsules (KNO3: 12 mmol giving 744 mg of nitrate) for 5 days
Drug: Potassium Nitrate
Potassium nitrate capsules (KNO3: 12 mmol giving 744 mg of nitrate) for 5 days

Placebo Comparator: Potassium Chloride
Potassium Chloride
Drug: Potassium Chloride
Potassium Chloride capsules for 5 days




Primary Outcome Measures :
  1. Contrast Induced Nephropathy [ Time Frame: 48-72 hours ]
    Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria


Secondary Outcome Measures :
  1. Demonstration of a persistent benefit of dietary inorganic nitrate against long-term renal impairment [ Time Frame: 3 months ]
    Difference in real function as measured by eGFR (estimated glomerular filtration rate) at 3 months post-contrast exposure

  2. Measurement of Circulating Nitrite and Nitrate levels [ Time Frame: Baseline, and at 6 hours, 48 hours and 3 months following treatment. ]
    Plasma Nitrite/Nitrate levels

  3. Major Adverse Cardiac Events [ Time Frame: 3 and 12 months follow-up ]
    Defined as death, non-fatal myocardial infarction, revascularisation, acute heart failure, non-fatal stroke

  4. Cost effectiveness of dietary inorganic Nitrate [ Time Frame: 1 year ]
    Incremental Cost Effectiveness Ratio (ICER)

  5. To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by urinary renal biomarkers [ Time Frame: 4-6 hours ]
    Measurement of urinary IGFB7/TIMP-2

  6. To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by serum biomarkers [ Time Frame: 4-6 hours ]
    Measurement of serum Neutrophil gelatinase-associated lipocalin (NGAL)

  7. To determine if dietary inorganic nitrate decreases rates of post-procedural Myocardial Infarction [ Time Frame: 6-12 hrs ]
    Definition as per Society for Cardiovascular Angiography and Interventions (SCAI)



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03627130


Contacts
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Contact: Daniel Jones, MRCP, PhD 020 7882 8377 daniel.jones@qmul.ac.uk
Contact: Amrita Ahluwalia, PhD 020 7882 8377 a.ahluwalia@qmul.ac.uk

Locations
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United Kingdom
Barts Heart Centre Recruiting
London, United Kingdom, EC1A 7BE
Contact: Mervyn Andiapen    02037658707    mervyn.andiapen@bartshealth.nhs.uk   
Sponsors and Collaborators
Barts & The London NHS Trust
Investigators
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Principal Investigator: Amrita Ahluwalia, PhD Queen Mary University of London

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Responsible Party: Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT03627130     History of Changes
Other Study ID Numbers: 18/1
First Posted: August 13, 2018    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The trial protocol will be published prior to the commencement of the study
Supporting Materials: Study Protocol
Time Frame: Mid-late 2018
Access Criteria: Freely available via journal

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Barts & The London NHS Trust:
Percutaneous Coronary Intervention
Nitric Oxide
Nitrite
Acute Kidney Injury
Acute Coronary Syndrome

Additional relevant MeSH terms:
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Syndrome
Acute Coronary Syndrome
Kidney Diseases
Acute Kidney Injury
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Urologic Diseases
Renal Insufficiency