Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

September 25, 2018 updated by: Ahmed Zaky, University of Alabama at Birmingham

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Birmingham, Alabama, United States, 35249
        • UAB Department of Anesthesiology and Perioperative Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control group
saline infusion will be administered after induction of general anesthesia
A placebo (saline infusion) will be administered after induction of general anesthesia.
Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
Other Names:
  • NaNO2
Active Comparator: Sodium Nitrite
sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
A placebo (saline infusion) will be administered after induction of general anesthesia.
Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
Other Names:
  • NaNO2

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Ahmed F Zaky, MD, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2018

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

December 1, 2020

Study Registration Dates

First Submitted

October 20, 2017

First Submitted That Met QC Criteria

October 31, 2017

First Posted (Actual)

November 6, 2017

Study Record Updates

Last Update Posted (Actual)

September 27, 2018

Last Update Submitted That Met QC Criteria

September 25, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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