Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

Phase 3

Withdrawn

• Conditions: Acute Kidney Injury
• Interventions: Drug: Saline; Drug: Sodium Nitrite

• Registration Number: NCT03331146
• Lead Sponsor: University of Alabama at Birmingham

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.

Study Timeline

• Study First Submitted: 2017-10-20
• Study First Submitted QC: 2017-10-31
• Study First Posted: 2017-11-06
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-25
• Last Update Posted: 2018-09-27
• Study Start: 2018-10-01
• Primary Completion: 2019-06-01
• Study Completion: 2020-12-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium Nitrite	Saline	sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
Control group	Saline	saline infusion will be administered after induction of general anesthesia
Sodium Nitrite	Sodium Nitrite	sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
Control group	Sodium Nitrite	saline infusion will be administered after induction of general anesthesia

Primary Outcome Measures

Name	Time	Method
Nitrite Metabolome Levels	baseline to 73 hrs post-operatively	Measuring nitrite, nitrate, and nitrosothiols levels
Biomarkers of Hemolysis	baseline to 73 hrs post-operatively	Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin
Biomarkers of Kidney Injury	baseline to 73 hrs post-operatively	Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)
Cell Cycle Stress	baseline to 73 hrs post-operatively	Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7

Secondary Outcome Measures

Name	Time	Method
Vasopressors Usage	baseline to 73 hrs post-operatively	Percentage of vasopressor usage between the control and intervention
Biomarkers of Kidney Injury	baseline to 24 hours post-operatively	Measuring kidney injury indicators creatine, neutrophil, lipocalin (NGAL)
Cell Cycle Stress	baseline to 24 hours post-operatively	Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
Biomarkers of Myocardial Injury	baseline to 24 hours post-operatively	Measuring myocardial injury indicators troponin and CKMB
Urine Output	baseline to 73 hrs post-operatively	Measuring total urine output
Biomarkers of Hepatic injury	baseline to 24 hours post-operatively	Measuring serum AST and ALT

Trial Locations

Locations (1)

UAB Department of Anesthesiology and Perioperative Medicine; 🇺🇸 Birmingham, Alabama, United States