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Completed

NCT Number: NCT02361944

Risk of Oxygen During Cardiac Surgery Trial

The investigators will recruit and randomize 200 elective cardiac surgery patients to receive physiologic oxygenation (normoxia) or hyper-oxygenation (hyperoxia) during surgery to test the hypothesis that intraoperative physiologic oxygenation decreases the generation of reactive oxygen species, oxidative damage, and postoperative organ injury compared to hyper-oxygenation.

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Open-heart cardiac surgery, defined as surgery on the heart or aorta that requires sternotomy or thoracotomy.

Exclusion criteria

  • Current acute coronary syndrome (defined as ST elevation myocardial infarction or non-ST elevation myocardial infarction (troponin leak within 72 hours of surgery or consent +/- EKG changes consistent with myocardial ischemia)).
  • Home supplemental oxygen use.
  • Preoperative supplemental oxygen requirement to maintain arterial O2 sat of 92%.
  • Right to left intracardiac shunt including atrial septal defect and ventricular septal defect with Cor Pulmonale.
  • Carotid stenosis defined as >50% stenosis.
  • Cardiac surgery that requires intraoperative circulatory arrest, such as aortic arch replacement.
  • Current use of hemo- or peritoneal dialysis.
  • Pregnancy

Treatment and study plan

Oxygen - normoxia

Drug

Titration of FIO2 to maintain normal hemoglobin oxygen saturation (95-97%)

Other names: oxygen

Oxygen - hyperoxia

Drug

Administration of 1.0 FIO2 during ventilation and 0.8 or above during cardiopulmonary bypass

Other names: oxygen

Primary outcomes

  1. Intraoperative Systemic Oxidative Damage

    Time frame: separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    quantified by measuring F2-isoprostanes isofurans following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting

  2. Acute Kidney Injury

    Time frame: baseline to postoperative day 2

    quantified by change in serum creatinine concentration

Secondary outcomes

  1. Vascular Reactivity / Endothelial Function (as Measured by Flow Mediated Dilation)

    Time frame: ICU admission (immediately after arrival in ICU from operating room)

    brachial artery flow mediated dilation assessed when patient arrives in ICU after surgery. brachial artery flow mediated dilation is represented as the percent change in brachial artery diameter following 5 minutes of artery occlusion. The entire assessment takes place at ICU admission.

  2. Mitochondrial Function

    Time frame: up to 2 days following surgery

    mitochondrial function in atrial myocardium estimated by quantifying adenylate kinase at the end of surgery and oxygen intervention

  3. Number of People With Arrhythmia

    Time frame: from surgery to hospital discharge, average of 6 days following surgery

    defined as any atrial fibrillation following surgery until hospital discharge assessed using continuous telemetry, rhythm strips, and electrocardiograms

  4. Myocardial Injury or Infarction

    Time frame: morning of postoperative day 1

    plasma concentration of creatine kinase, myocardial band

  5. Number of People With Stroke

    Time frame: from surgery to hospital discharge, average of 6 days following surgery

    Defined as new deficit on neurologic exam and confirmed with radiologic evidence occurring at any point prior to hospital discharge

  6. Postoperative Cognitive Dysfunction

    Time frame: up to 18 months following surgery

    Median change scores at the Short Blessed Scale (SBT) administered one-year following surgery. The SBT is a validated rating scale, administered by the clinician, measuring the cognitive performance. Sum Total (range 0-28) with 0 indicating no cognitive impairment and 28 indicating severe cognitive impairment.

  7. Respiratory Failure

    Time frame: from surgery to hospital discharge, average of 6 days following surgery

    reintubation

  8. Chronic Kidney Disease

    Time frame: 12 months following surgery

    eGFR one year following surgery

  9. Inflammation

    Time frame: up to 2 days following surgery

    Estimated by quantifying plasma concentration of plasminogen activator inhibitor-1 (PAI-1)

  10. Hemolysis

    Time frame: separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    plasma free hemoglobin

  11. Reactive Oxygen Species Production

    Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    TMH electron spin probe

  12. Acute Brain Dysfunction (Delirium)

    Time frame: from surgery to hospital discharge, average of 6 days following surgery

    The number of participants with acute brain dysfunction as assessed by the Confusion Assessment Method for the ICU (CAM-ICU) twice daily while patients are in the ICU or for first 3 postoperative days.

  13. Oxygenation and Perfusion (Lactate)

    Time frame: ICU admission (immediately after arrival in ICU from operating room)

    arterial lactate measured from arterial blood collected at ICU admission (immediately after arrival in ICU from operating room)

  14. Acute Kidney Injury, According to KDIGO Criteria

    Time frame: up to 7 days following surgery

    KDIGO acute kidney injury is defined as an increase in SCr ≥ 0.3 mg/dL (≥ 26.5 lmol/L) within 48 hours of surgery or 1.5 to 1.9 times baseline within 7 days of surgery

  15. Acute Kidney Injury Estimated by Urine Concentration of TIMP-2 IGFBP7

    Time frame: baseline to 2 days following surgery

    Urinary concentration of [TIMP2]*[IGFBP7] 6 hours after ICU admission

  16. Acute Kidney Injury Estimated by Urine Concentration of NGAL

    Time frame: baseline to 2 days following surgery

    Urinary concentration of neutrophil gelatinase-associated lipocalin (NGAL) 6 hours after ICU admission.

  17. Reactive Oxygen Species Production

    Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    CAT1H electron spin probe

  18. Oxygenation and Perfusion (SpO2)

    Time frame: during surgery

    hemoglobin O2 saturation summarized using SpO2 data continuously measured and recorded every minute during surgery. We calculated the median SpO2 throughout surgery using all the minute to minute values. For example, if a participant had a 5 hour (300 minutes) long surgery, the participant would have 300 SpO2 measurements. We calculated and report the median of those measurements.

  19. Oxygenation and Perfusion (PaO2)

    Time frame: end of surgery, defined as separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    partial pressure of oxygen in arterial blood measured from blood sampled at end of surgery, defined as following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

  20. Oxygenation and Perfusion (Cerebral Oximetry)

    Time frame: continuously assessed throughout surgery and recorded each minute

    brain hemoglobin oxygenation using near-infrared spectroscopy (NIRS). The median percent changes from baseline (baseline measured at beginning of surgery when probes placed on forehead, prior to intervention) throughout surgery was calculated using cerebral oximetry measurements collected every minute throughout surgery. We calculated the difference between baseline and each measurement throughout surgery. For example, if a participant had a 5 hour (300 minutes) long surgery, the participant would have 300 cerebral oximetry measurements. We calculated and report the median of those measurements.

  21. Oxygenation and Perfusion (SvO2)

    Time frame: end of surgery, defined as following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    mixed venous O2 saturation, measured from blood sampled from pulmonary artery sampled at end of surgery, defined as following separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

  22. Oxygenation and Perfusion (Cardiac Index)

    Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    cardiac output (normalized to body surface area, i.e., cardiac index)

  23. Vascular Reactivity / Endothelial Function (Peripheral Artery Tonometry)

    Time frame: ICU admission (immediately after arrival in ICU from operating room)

    reactive hyperemia index measured at ICU admission (immediately after arrival in ICU from operating room). The reactive hyperemia index is a number generated by an endopat machine performing peripheral artery tonometry. The index ranges from approximately 1-3, where higher values indicate better vascular reactivity and endothelial function.

  24. Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Dependent Vasodilation, EC50)

    Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention

    Effective concentration for 50% dilation acetylcholine dose response, tension wire myography from arterioles dissected from epicardial fat

  25. Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Dependent Vasodilation, Emax)

    Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention

    Maximum percentage of arteriole dilation after increasing doses of acetylcholine measured using tension wire myography of arterioles dissected from epicardial fat. The fat sample was collected during surgery when heart is exposed approximately 2 hours into intervention.

  26. Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Independent Vasodilation, EC50)

    Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention

    Effective concentration for 50% dilation sodium nitroprusside dose response, tension wire myography from arterioles dissected from epicardial fat

  27. Vascular Reactivity / Endothelial Function (Tension Wire Myography, Endothelial Independent Vasodilation, Emax)

    Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention

    Maximum percentage of arteriole dilation after increasing doses of sodium nitroprusside measured using tension wire myography of arterioles dissected from epicardial fat. The fat sample was collected during surgery when heart is exposed approximately 2 hours into intervention.

  28. Vascular Reactivity / Endothelial Function (Tension Wire Myography, sGC Activation Vasodilation, EC50)

    Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention

    Effective concentration for 50% dilation cinaciguat dose response, tension wire myography from arterioles dissected from epicardial fat

  29. Vascular Reactivity / Endothelial Function (Tension Wire Myography, sGC Activation Vasodilation, Emax)

    Time frame: tissue collected during surgery when heart is exposed approximately 2 hours into intervention

    Maximum percentage of arteriole dilation after increasing doses of cinaciguat measured using tension wire myography of arterioles dissected from epicardial fat. The fat sample was collected during surgery when heart is exposed approximately 2 hours into intervention.

  30. Vascular Reactivity / Endothelial Function (PAI-1)

    Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    Plasminogen activator inhibitor 1

  31. Vascular Reactivity / Endothelial Function (E-selectin)

    Time frame: end of surgery, defined as immediately after separation from cardiopulmonary bypass or completion of off-pump coronary artery bypass grafting (approximately 3-5 hours into surgery and intervention)

    E-selectin

Sponsors and collaborators

Lead sponsor

Vanderbilt University

Other

Collaborators

  • National Institute of General Medical Sciences (NIGMS)

Registry information

Official study title

Risk of Oxygen During Cardiac Surgery (ROCS) Trial

Acronym: ROCS

Important dates

Study start
2016
Primary completion
2020
Study completion
2021
First posted
Feb 12, 2015
Registry last updated
Feb 1, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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