Clinical trial NCT07016074: Inorganic Nitrate (NaNO3) Prevention of Contrast-Associated Acute Kidney Injury
Official title: Inorganic Nitrate (NaNO3) Prevention of Contrast-Associated Acute Kidney Injury
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Kidney Injury, Acute
Keywords: Sodium Nitrate
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2025-06-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This pilot study is designed to test the logistics and recruitment of a trial testing the benefit of sodium nitrate in the prevention of contrast-associated kidney injury in a group of patients at high-risk.


Eligibility criteria: Inclusion Criteria:

* Planned coronary angiogram or contrast-enhanced CT scan.
* High-risk for contrast-associated acute kidney injury (AKI) with creatine/Glomerular filtration rate (GFR) within 90 days as defined as:

  1. Undergoing coronary angiogram with GFR \<45 mL/min/1.73m2 OR
  2. Undergoing coronary angiogram with GFR \<60 mL/min/1.73m2 and concurrent risk of AKI as defined by Hamilton et al. BMC2 risk prediction model ≥ 7%.

     OR
  3. Undergoing contrast-enhanced CT scan with GFR\<45 mL/min/1.73m2
* If subject is a woman of child-bearing potential, subject agrees to the use of highly effective contraception starting at screening and during study participation.
* Ability to take oral medication and be willing to adhere to the study intervention regimen.
* Ability to understand and willingness to agree to an informed consent

Exclusion Criteria:

* Already fulfilling definition of acute kidney injury prior to contrast exposure by kidney disease improving global outcomes (KDIGO) criteria (absolute increase in creatinine from baseline of 0.3mg/dL or more OR relative increase in creatine of 50% or more from baseline).
* Primary indication for Percutaneous Coronary Intervention (PCI) including acute ST-segment elevation myocardial infarction
* End-stage renal disease actively on dialysis.
* Received any intravenous or intraarterial contrast within five days from planned contrast administration.
* Cardiac arrest within 14 days of planned contrast administration.
* Systolic blood pressure \< 100mmHg or diastolic blood pressure \<60mmHg OR currently receiving inotropes or vasopressors for hemodynamic support.
* History of hypersensitivity or known allergy to any of the components of the investigational product or placebo including sodium nitrate, inorganic nitrate, beet root juice, or lactose. This does not include lactose intolerance.
* Pregnancy or nursing female
* Participation in other investigational trials within the past 30 days prior to enrollment.
* Use of tadalafil within 48 hours, sildenafil or vardenafil within 24 hours, and avanafil within 12 hours of initiation of trial medication. If participant is on continuous dosing of tadalafil, sildenafil, vardenafil, or avanafil, they will be excluded from the trial. If participant is on intermittent dosing of tadalafil, sildenafil, vardenafil, or avanafil, patient agrees to withhold use of medication for duration of medication treatment extending 48 hours after the final dose.

Primary outcomes:
measure: Percent of participants receiving the first dose of blinded study drug within 1-8 hours prior to contrast exposure
timeFrame: Approximately 34 days
measure: Percent of participants completing full course of 4 doses of blinded study drug
timeFrame: Approximately 34 days
measure: Percent of participants with 48-hour basic metabolic panel collected between 36-60 hours of contrast exposure
timeFrame: Approximately 34 days
measure: Percent of participants who had completion of clinical outcome monitoring at 30-day follow-up interview
timeFrame: Approximately 34 days
measure: Percent of participants recruited to the trial for undergoing coronary angiogram
timeFrame: Approximately 34 days
measure: Percent of participants recruited to the trial for undergoing a contrast-enhanced CT scan
timeFrame: Approximately 34 days
Secondary outcomes:
measure: Number of participants who develop of Contrast-Associated Acute Kidney Injury (CA-AKI)
timeFrame: Approximately 34 days
measure: Number of participants who had initiation of renal replacement therapy within 30 days of planned contrast administration for patients that did not have active need for dialysis prior to study enrollment
timeFrame: Approximately 34 days
measure: Number of participants with all-cause mortality within 30 days of planned contrast administration as defined by cessation of life due to any cause
timeFrame: Approximately 34 days
measure: Number of participants with major adverse cardiovascular events (MACE)
timeFrame: Approximately 34 days
measure: Number of participants with cardiovascular death within 30 days of planned contrast administration as defined by cessation of life deemed secondary to cardiovascular cause
timeFrame: Approximately 34 days
measure: Number of participants with non-fatal myocardial infarction within 30 days of planned contrast administration
timeFrame: Approximately 34 days
measure: Number of participants with non-fatal stroke within 30 days of planned contrast administration
timeFrame: Approximately 34 days
measure: Number of participants with major adverse kidney events (MAKE)
timeFrame: Approximately 34 days
measure: Number of participants with persistent renal dysfunction at 30 days of planned contrast administration
timeFrame: Approximately 34 days
measure: Number of participants with new onset hypotension
timeFrame: Approximately 34 days
measure: Number of adverse events within 30 days of planned contrast administration
timeFrame: Approximately 34 days
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Hitinder Gurm, MBBS
role: STUDY_CHAIR
affiliation: University of Michigan
name: David Hamilton, MD
role: PRINCIPAL_INVESTIGATOR
References: