Clinical trial NCT03331146: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
Official title: Randomized, Controlled, Double-blinded Pilot Study: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Acute Kidney Injury
Keywords: Nitric Oxide
Sodium Nitrite
Cardiopulmonary bypass
cardioplegic cardiac arrest
coronary revacularization
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2017-11-06
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The main objective of this study is to evaluate the efficacy of intravenous sodium nitrite compared with placebo in reducing the occurrence of CSA-AK as diagnosed by KDIGO criteria during the first 72 hrs after cardiac surgery in high-risk patients undergoing cardiac surgery. Secondary objectives are to determine whether IV sodium nitrite achieves adequate pharmacokinetics (PK) in patients undergoing cardiac surgery with the use of CPB.

Detailed description: Acute kidney injury is one of the most untoward consequences of cardiac-surgery with the use of CPB. As such it is associated with a high mortality and morbidity and health care expense. Unfortunately, currently, there is no effective preventive or treatment strategy for cardiac surgery-associated (CSA) AKI other than renal replacement therapy.

It is postulated that a major mechanism of CSA-AKI is created by the ischemia reperfusion injury (IRI) resulting from aortic cross clamping and unclamping. This creates a cascade of events culminating in inflammation, microvascular dysfunction and tubular cell maladaptation and eventually renal tissue damage. Current treatment modalities that target the microcirculation such as blood pressure and cardiac output fails to prevent renal abnormalities and as such may be deleterious to the renal tissue microcirculation. The PI hypothesizes that a therapeutic strategy that limits IRI such as the administration of inhaled nitric oxide (NO) or sodium nitrite (NaNO2) would ameliorate CSA-AKI by limiting inflammatory injury to the kidney.

The anion nitrite (NO2-) releases NO in biological systems and has been demonstrated to inhibit IR injury in the heart, liver and kidneys created by various pathologic states1-3 and improve outcomes in patients with acute myocardial infarction, in patients with pulmonary hypertension and is the putative active mediator of protection in liver-transplantation patients receiving inhaled nitric oxide4.

The objective of this study is to determine whether the NO donor, nitrite will prevent I/R injury in patients at high risk of development of CSA-AKI undergoing open-heart surgery with cardiopulmonary bypass.

Eligibility criteria: Inclusion Criteria:

* Patients CCFS score ≥ 6 (Table 1)
* Patients admitted to UAB cardiac intensive care unit (CICU) following elective cardiac surgery with cardiopulmonary bypass under general endotracheal anesthesia
* 19 years old
* Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2

Exclusion Criteria:

* Prisoners directly admitted from a correctional facility.
* Children \< 19 years or under 50 kg body weight if age is unknown.
* Patients enrolled in a concurrent ongoing interventional, randomized clinical trial.
* Patients with end stage renal disease or preexisting GFR \<30 mL/min/1.73 m2 or need for dialysis. 34
* Patients with end stage heart disease on the cardiac transplant list.
* Patients undergoing procedures without the use of CPB
* All transplant patients.
* Patients on ventricular assist devices.
* Patients undergoing emergency procedures.
* Patients with glucose 6-dehydrogenase deficiency
* Pregnancy

Primary outcomes:
measure: Nitrite Metabolome Levels
timeFrame: baseline to 73 hrs post-operatively
measure: Biomarkers of Hemolysis
timeFrame: baseline to 73 hrs post-operatively
measure: Biomarkers of Kidney Injury
timeFrame: baseline to 73 hrs post-operatively
measure: Cell Cycle Stress
timeFrame: baseline to 73 hrs post-operatively
Secondary outcomes:
measure: Biomarkers of Hepatic injury
timeFrame: baseline to 24 hours post-operatively
measure: Biomarkers of Kidney Injury
timeFrame: baseline to 24 hours post-operatively
measure: Cell Cycle Stress
timeFrame: baseline to 24 hours post-operatively
measure: Biomarkers of Myocardial Injury
timeFrame: baseline to 24 hours post-operatively
measure: Urine Output
timeFrame: baseline to 73 hrs post-operatively
measure: Vasopressors Usage
timeFrame: baseline to 73 hrs post-operatively
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Department of Anesthesiology and Perioperative Medicine
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Ahmed F Zaky, MD
role: PRINCIPAL_INVESTIGATOR
References: