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Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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Recruitment Status : Withdrawn (Principal Investigator made aware of similar studies that have already been published.)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

Tracking Information
First Submitted Date  ICMJE October 20, 2017
First Posted Date  ICMJE November 6, 2017
Last Update Posted Date September 27, 2018
Estimated Study Start Date  ICMJE October 1, 2018
Estimated Primary Completion Date June 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2017)
  • Nitrite Metabolome Levels [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring nitrite, nitrate, and nitrosothiols levels
  • Biomarkers of Hemolysis [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin
  • Biomarkers of Kidney Injury [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)
  • Cell Cycle Stress [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
Original Primary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • Nitrite Metabolome [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring nitrite, nitrate, and nitrosothiols levels
  • Hemolysis [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin
  • Kidney Injury [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)
  • Stress [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2017)
  • Biomarkers of Hepatic injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring serum AST and ALT
  • Biomarkers of Kidney Injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring kidney injury indicators creatine, neutrophil, lipocalin (NGAL)
  • Cell Cycle Stress [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
  • Biomarkers of Myocardial Injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring myocardial injury indicators troponin and CKMB
  • Urine Output [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring total urine output
  • Vasopressors Usage [ Time Frame: baseline to 73 hrs post-operatively ]
    Percentage of vasopressor usage between the control and intervention
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • Hepatic injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring serum AST and ALT
  • Kidney Injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring kidney injury indicators creatine, neutrophil, lipocalin (NGAL)
  • Stress [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
  • Myocardial Injury [ Time Frame: baseline to 24 hours post-operatively ]
    Measuring myocardial injury indicators troponin and CKMB
  • Urine Output [ Time Frame: baseline to 73 hrs post-operatively ]
    Measuring total urine output
  • Vasopressors [ Time Frame: baseline to 73 hrs post-operatively ]
    Determining the use of vasopressors in both treatment groups
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
Official Title  ICMJE Randomized, Controlled, Double-blinded Pilot Study: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Acute Kidney Injury
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Placebo Comparator: Control group
    saline infusion will be administered after induction of general anesthesia
    Interventions:
    • Drug: Saline
    • Drug: Sodium Nitrite
  • Active Comparator: Sodium Nitrite
    sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
    Interventions:
    • Drug: Saline
    • Drug: Sodium Nitrite
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: September 25, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2017)
40
Estimated Study Completion Date  ICMJE December 1, 2020
Estimated Primary Completion Date June 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03331146
Other Study ID Numbers  ICMJE 1709284471
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ahmed Zaky, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ahmed F Zaky, MD University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP