Kidney Injury, Acute
Conditions
Keywords
Sodium Nitrate
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.
Detailed description
The timing of the follow-up blood test was changed from 48 hours (± 12 hours) to 72 hours (± 36 hours) after contrast exposure. This change allows participants more flexibility to complete their lab work at a convenient outpatient location without requiring a return visit within a narrow time window. The new timing still falls within the period when kidney function changes from contrast exposure would be expected to appear, so the study's ability to detect these changes is preserved and safety monitoring remains consistent.
Interventions
DRUGSodium Nitrate
The study drug is sodium nitrate capsule at a dose of 12mmol of nitrate. This medication will be given orally 1-8 hours before the planned contrast administration and then once per day for a total of four doses.
DRUGPlacebo
The placebo control medication will be a capsule filled with lactose that will be taken in the same manner and schedule as the sodium nitrate capsule
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of participants receiving the first dose of blinded study drug within 1-8 hours prior to contrast exposure | Approximately 34 days | Success is defined as greater than 80% of patients receiving the first dose of blind study drug within 1-8 hours prior to contrast exposure. |
| Percent of participants completing full course of 4 doses of blinded study drug | Approximately 34 days | Success is defined as greater than 80% of patients completing the full course of 4 doses of blinded study drug |
| Percent of participants with 48-hour basic metabolic panel collected between 36-108 hours of contrast exposure | Approximately 34 days | Success is defined as greater than 80% of patients having appropriately collected 48-hour basic metabolic panel collected 36-108 hours of contrast exposure |
| Percent of participants who had completion of clinical outcome monitoring at 30-day follow-up interview | Approximately 34 days | Success is defined as greater than 80% of patients completing full clinical outcome monitoring at 30-day follow-up interview. |
| Percent of participants recruited to the trial for undergoing coronary angiogram | Approximately 34 days | Success is defined as four or more patients being recruited into the study prior to coronary angiogram each month of the study averaged over the study period |
| Percent of participants recruited to the trial for undergoing a contrast-enhanced CT scan | Approximately 34 days | Success is defined as four or more patients being recruited into the study prior to contrast-enhanced CT scan each month of the study averaged over the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who develop of Contrast-Associated Acute Kidney Injury (CA-AKI) | Approximately 34 days | As defined by creatinine measurement at 48 hours after contrast administration meeting Kidney Disease Improving Global Outcomes (KDIGO) criteria |
| 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 | Approximately 34 days | — |
| Number of participants with all-cause mortality within 30 days of planned contrast administration as defined by cessation of life due to any cause | Approximately 34 days | — |
| Number of participants with major adverse cardiovascular events (MACE) | Approximately 34 days | MACE is a composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke within 30 days of planned contrast administration |
| Number of participants with cardiovascular death within 30 days of planned contrast administration as defined by cessation of life deemed secondary to cardiovascular cause | Approximately 34 days | — |
| Number of participants with non-fatal myocardial infarction within 30 days of planned contrast administration | Approximately 34 days | — |
| Number of participants with non-fatal stroke within 30 days of planned contrast administration | Approximately 34 days | — |
| Number of participants with major adverse kidney events (MAKE) | Approximately 34 days | MAKE is a composite outcome of death, new renal replacement therapy, or persistent renal dysfunction within 30 days of planned contrast administration. Persistent renal dysfunction is defined as creatinine value greater than or equal to 200% of baseline value at 30 days |
| Number of participants with persistent renal dysfunction at 30 days of planned contrast administration | Approximately 34 days | Renal dysfunction is defined as creatinine value greater than or equal to 200% of baseline value at 30 days. |
| Number of participants with new onset hypotension | Approximately 34 days | — |
| Number of adverse events within 30 days of planned contrast administration | Approximately 34 days | — |
Countries
United States
Contacts
CONTACTAllison Schley
STUDY_CHAIRHitinder Gurm, MBBS
University of Michigan
PRINCIPAL_INVESTIGATORDavid Hamilton, MD
University of Michigan
Outcome results
None listed