Contrast-induced NephropathyPhase 2NITRATE-CINNCT03627130
The Use of Inorganic Nitrate for the Prevention of Contrast-induced Nephropathy
A Phase 2 study testing Potassium Nitrate and Potassium Chloride in people with Contrast-induced Nephropathy and Acute Kidney Injury, run by Barts & The London NHS Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Contrast-induced Nephropathy, Acute Kidney Injury, Acute Coronary Syndrome
- What is being tested?
- Potassium Nitrate and Potassium Chloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 640 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Nov 2018to 30 May 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- Severe acute infection
- Pregnancy
- Breast-feeding mothers.
- Any Inclusion Criteria not met
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- Potassium Nitrate, Potassium Chloride
- Keywords
- Percutaneous Coronary Intervention, Nitric Oxide, Nitrite, Acute Kidney Injury, Acute Coronary Syndrome
- Medical subject headings
- Acute Kidney Injury, Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Potassium NitrateDrug
Potassium nitrate capsules (KNO3: 12 mmol giving 744 mg of nitrate) for 5 days
Potassium ChlorideDrug
Potassium Chloride capsules for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Potassium Nitrate | Active comparator | Potassium nitrate capsules (KNO3: 12 mmol giving 744 mg of nitrate) for 5 days Receives: Drug: Potassium Nitrate |
| Potassium Chloride | Placebo comparator | Potassium Chloride Receives: Drug: Potassium Chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Contrast Induced Nephropathy
Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Measured: 48-72 hours
Secondary outcomes (7)
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
Measured: 3 months
Measurement of Circulating Nitrite and Nitrate levels
Plasma Nitrite/Nitrate levels
Measured: Baseline, and at 6 hours, 48 hours and 3 months following treatment.
Major Adverse Cardiac Events
Defined as death, non-fatal myocardial infarction, revascularisation, acute heart failure, non-fatal stroke
Measured: 3 and 12 months follow-up
Cost effectiveness of dietary inorganic Nitrate
Incremental Cost Effectiveness Ratio (ICER)
Measured: 1 year
To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by urinary renal biomarkers
Measurement of urinary IGFB7/TIMP-2
Measured: 4-6 hours
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)
Measured: 4-6 hours
To determine if dietary inorganic nitrate decreases rates of post-procedural Myocardial Infarction
Definition as per Society for Cardiovascular Angiography and Interventions (SCAI)
Measured: 6-12 hrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2018
- Study start29 Nov 2018
- Primary completion30 May 2022
- Study completion30 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Contrast-induced NephropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 640 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amrita Ahluwalia, PhD, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03627130
- Sponsor's protocol ID
- 18/1
- Acronym
- NITRATE-CIN
- Status last verified
- Dec 2022
- First submitted
- 17 Jan 2018
- Last updated
- 16 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The trial protocol will be published prior to the commencement of the study
Publications
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.
PubMed 38513060Beirne 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.
PubMed 33764198
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03627130
- Acronym / sponsor ID
- NITRATE-CIN / 18/1
- Keywords
- Percutaneous Coronary Intervention, Nitric Oxide, Nitrite, Acute Kidney Injury, Acute Coronary Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 640 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Study start
- 29 Nov 2018 (actual)
- Primary completion
- 30 May 2022 (actual)
- Study completion
- 30 May 2022 (actual)
- First posted
- 13 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Potassium Nitrate | Active comparator | Drug: Potassium NitratePotassium nitrate capsules (KNO3: 12 mmol giving 744 mg of nitrate) for 5 days |
| Potassium Chloride | Placebo comparator | Drug: Potassium ChloridePotassium Chloride |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Potassium NitratePotassium nitrate capsules (KNO3: 12 mmol giving 744 mg of nitrate) for 5 days | Drug | Potassium Nitrate |
| Potassium ChloridePotassium Chloride capsules for 5 days | Drug | Potassium Chloride |
Primary outcome
Contrast Induced Nephropathy
Time frame: 48-72 hours
Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria
7 secondary outcomes
Demonstration of a persistent benefit of dietary inorganic nitrate against long-term renal impairment
Time frame: 3 months
Measurement of Circulating Nitrite and Nitrate levels
Time frame: Baseline, and at 6 hours, 48 hours and 3 months following treatment.
Major Adverse Cardiac Events
Time frame: 3 and 12 months follow-up
Cost effectiveness of dietary inorganic Nitrate
Time frame: 1 year
To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by urinary renal biomarkers
Time frame: 4-6 hours
To determine if dietary inorganic nitrate ingestion decreases sub-clinical renal injury as measured by serum biomarkers
Time frame: 4-6 hours
To determine if dietary inorganic nitrate decreases rates of post-procedural Myocardial Infarction
Time frame: 6-12 hrs
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2022.
- Derived from this study: PubMed 38513060Jones 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.
- Derived from this study: PubMed 33764198Beirne 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.
- Individual participant dataSharing planned: Yes. The trial protocol will be published prior to the commencement of the study
Related trials for Contrast-induced Nephropathy
Recruiting
Effectiveness of Remote Ischemic Preconditioning for Prevention of Contrast Induced Acute Kidney Injury in Patients Undergoing Coronary Angiograms.
Contrast-induced Acute Kidney Injury (CI-AKI) Following Coronary Angiogram (CI-AKI), Contrast-induced Nephropathy Following Coronary Angiogram (CIN)
Not yet recruitingObservational study
Uric Acid to Albumin Ratio for Predicting Contrast Associated Acute Kidney Injury After Cardiac and Non Cardiac Procedures
Contrast-Induced Nephropathy, Acute Kidney Injury
Not yet recruitingObservational study
Beyond the Mehran Risk Score: Predictive Value of Total Ischemic Time for Contrast-Induced Nephropathy in ST Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention.
ST Elevation (STEMI) Myocardial Infarction, Contrast Induced Nephropathy (CIN)
Not yet recruitingObservational study
Contrast Volume as a Predictor of Kidney Injury Following Contrast-Enhanced CT
Contrast-Associated Acute Kidney Injury, Acute Kidney Injury
Not yet recruitingObservational study
Serum Electrolytes and Contrast-Induced Nephropathy in Acute Ischemic Stroke Patients Undergoing Endovascular Treatment
Acute Ischemic Stroke, Contrast-induced Nephropathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amrita Ahluwalia, PhD principal investigator
Queen Mary University of London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Potassium Nitrate and Potassium Chloride in people with Contrast-induced Nephropathy and Acute Kidney Injury, run by Barts & The London NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Contrast Induced Nephropathy (time frame: 48-72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03627130, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2022; AzTrials last refreshed its copy on 8 Nov 2026.