Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

NCT ID: NCT03331146

Last Updated: 2018-09-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-01
• Study Completion Date: 2020-12-01

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.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Control group

saline infusion will be administered after induction of general anesthesia

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

A placebo (saline infusion) will be administered after induction of general anesthesia.

Sodium Nitrite

Intervention Type: DRUG

Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs.

Sodium Nitrite

sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.

Group Type: ACTIVE_COMPARATOR

Saline

Intervention Type: DRUG

A placebo (saline infusion) will be administered after induction of general anesthesia.

Sodium Nitrite

Intervention Type: DRUG

Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs.

Interventions

Saline

A placebo (saline infusion) will be administered after induction of general anesthesia.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

NaNO2

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Zaky

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed F Zaky, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

UAB Department of Anesthesiology and Perioperative Medicine

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

1709284471

Identifier Type: -

Identifier Source: org_study_id