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Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

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ClinicalTrials.gov Identifier: NCT03331146
Recruitment Status : Withdrawn (Principal Investigator made aware of similar studies that have already been published.)
First Posted : November 6, 2017
Last Update Posted : September 27, 2018
Sponsor:
Information provided by (Responsible Party):
Ahmed Zaky, 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.

Condition or disease Intervention/treatment Phase
Acute Kidney Injury Drug: Saline Drug: Sodium Nitrite Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Randomized, Controlled, Double-blinded Pilot Study: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
Estimated Study Start Date : October 1, 2018
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Control group
saline infusion will be administered after induction of general anesthesia
Drug: Saline
A placebo (saline infusion) will be administered after induction of general anesthesia.

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.
Other Name: NaNO2

Active Comparator: Sodium Nitrite
sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
Drug: Saline
A placebo (saline infusion) will be administered after induction of general anesthesia.

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.
Other Name: NaNO2




Primary Outcome Measures :
  1. Nitrite Metabolome Levels [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring nitrite, nitrate, and nitrosothiols levels

  2. Biomarkers of Hemolysis [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin

  3. Biomarkers of Kidney Injury [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)

  4. Cell Cycle Stress [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7


Secondary Outcome Measures :
  1. Biomarkers of Hepatic injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring serum AST and ALT

  2. Biomarkers of Kidney Injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring kidney injury indicators creatine, neutrophil, lipocalin (NGAL)

  3. Cell Cycle Stress [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7

  4. Biomarkers of Myocardial Injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring myocardial injury indicators troponin and CKMB

  5. Urine Output [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring total urine output

  6. Vasopressors Usage [ Time Frame: baseline to 73 hrs post-operatively ]
    Percentage of vasopressor usage between the control and intervention



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Ages Eligible for Study:   19 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03331146


Locations
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United States, Alabama
UAB Department of Anesthesiology and Perioperative Medicine
Birmingham, Alabama, United States, 35249
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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Principal Investigator: Ahmed F Zaky, MD University of Alabama at Birmingham

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Responsible Party: Ahmed Zaky, Associate Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT03331146     History of Changes
Other Study ID Numbers: 1709284471
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: September 27, 2018
Last Verified: September 2018

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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

Keywords provided by Ahmed Zaky, University of Alabama at Birmingham:
Nitric Oxide
Sodium Nitrite
Cardiopulmonary bypass
cardioplegic cardiac arrest
coronary revacularization

Additional relevant MeSH terms:
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Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs