Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

Acute Kidney Injury Clinical Trial

Official title:

Randomized, Controlled, Double-blinded Pilot Study: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03331146
• Other study ID #: 1709284471
• Status: Withdrawn
• Phase: Phase 3
• Start date: October 1, 2018
• Est. completion date: December 1, 2020

Study information

• Verified date: September 2018
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 1, 2020
• Est. primary completion date: June 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury

Intervention

Drug:
• Saline
A placebo (saline infusion) will be administered after induction of general anesthesia.
• Sodium Nitrite
Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs.

Locations

Country	Name	City	State
United States	UAB Department of Anesthesiology and Perioperative Medicine	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nitrite Metabolome Levels	Measuring nitrite, nitrate, and nitrosothiols levels	baseline to 73 hrs post-operatively
Primary	Biomarkers of Hemolysis	Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin	baseline to 73 hrs post-operatively
Primary	Biomarkers of Kidney Injury	Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)	baseline to 73 hrs post-operatively
Primary	Cell Cycle Stress	Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7	baseline to 73 hrs post-operatively
Secondary	Biomarkers of Hepatic injury	Measuring serum AST and ALT	baseline to 24 hours post-operatively
Secondary	Biomarkers of Kidney Injury	Measuring kidney injury indicators creatine, neutrophil, lipocalin (NGAL)	baseline to 24 hours post-operatively
Secondary	Cell Cycle Stress	Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7	baseline to 24 hours post-operatively
Secondary	Biomarkers of Myocardial Injury	Measuring myocardial injury indicators troponin and CKMB	baseline to 24 hours post-operatively
Secondary	Urine Output	Measuring total urine output	baseline to 73 hrs post-operatively
Secondary	Vasopressors Usage	Percentage of vasopressor usage between the control and intervention	baseline to 73 hrs post-operatively