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Cardiac SurgeryPhase 2/3ROCSNCT02361944

Risk of Oxygen During Cardiac Surgery Trial

A Phase 2/3 study testing Oxygen - normoxia and Oxygen - hyperoxia in people with Cardiac Surgery, run by Vanderbilt University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cardiac Surgery
What is being tested?
Oxygen - normoxia and Oxygen - hyperoxia
Could I receive a placebo?
No, everyone receives an active treatment
How many people
213 participants
Where
1 siteUnited States
Study dates
5 Apr 2016to 8 Jan 2021
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

Other trials in United States

About this study

Official title: Risk of Oxygen During Cardiac Surgery (ROCS) 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.

Conditions
Cardiac Surgery
Being tested
Oxygen - normoxia, Oxygen - hyperoxia
Keywords
oxygen, hyperoxia, reactive oxygen species, oxidative stress, oxidative damage, endothelial function, vascular reactivity, mitochondrial function, surgery, anesthesia, kidney injury, renal failure, delirium, myocardial injury, arrythmia
Medical subject headings
Hyperoxia, Renal Insufficiency, Delirium, Arrhythmias, Cardiac

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oxygen - normoxiaDrug

    Also called oxygen

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

  • Oxygen - hyperoxiaDrug

    Also called oxygen

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

Study groups in NCT02361944
Study groupRoleWhat they receive
NormoxiaExperimentalOxygen administration to maintain a hemoglobin oxygen saturation of 95-97% or arterial PaO2 80-110 mmHg during surgery.
Receives: Drug: Oxygen - normoxia
HyperoxiaActive comparatorFraction of inspired oxygen 1.0 during mechanical ventilation and 0.8 during cardiopulmonary bypass during surgery.
Receives: Drug: Oxygen - hyperoxia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intraoperative Systemic Oxidative Damage

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

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

  2. Acute Kidney Injury

    quantified by change in serum creatinine concentration

    Measured: baseline to postoperative day 2

Secondary outcomes (31)
  1. Vascular Reactivity / Endothelial Function (as Measured by Flow Mediated Dilation)

    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.

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

  2. Mitochondrial Function

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

    Measured: up to 2 days following surgery

  3. Number of People With Arrhythmia

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

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

  4. Myocardial Injury or Infarction

    plasma concentration of creatine kinase, myocardial band

    Measured: morning of postoperative day 1

  5. Number of People With Stroke

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

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

  6. Postoperative Cognitive Dysfunction

    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.

    Measured: up to 18 months following surgery

  7. Respiratory Failure

    reintubation

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

  8. Chronic Kidney Disease

    eGFR one year following surgery

    Measured: 12 months following surgery

  9. Inflammation

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

    Measured: up to 2 days following surgery

  10. Hemolysis

    plasma free hemoglobin

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

  11. Reactive Oxygen Species Production

    TMH electron spin probe

    Measured: 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)

  12. Acute Brain Dysfunction (Delirium)

    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.

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

  13. Oxygenation and Perfusion (Lactate)

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

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

  14. Acute Kidney Injury, According to KDIGO Criteria

    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

    Measured: up to 7 days following surgery

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

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

    Measured: baseline to 2 days following surgery

  16. Acute Kidney Injury Estimated by Urine Concentration of NGAL

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

    Measured: baseline to 2 days following surgery

  17. Reactive Oxygen Species Production

    CAT1H electron spin probe

    Measured: 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)

  18. Oxygenation and Perfusion (SpO2)

    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.

    Measured: during surgery

  19. Oxygenation and Perfusion (PaO2)

    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)

    Measured: 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)

  20. Oxygenation and Perfusion (Cerebral Oximetry)

    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.

    Measured: continuously assessed throughout surgery and recorded each minute

  21. Oxygenation and Perfusion (SvO2)

    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)

    Measured: 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)

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

    Measured: 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)

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

    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.

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

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

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

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

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

    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.

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

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

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

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

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

    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.

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

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

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

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

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

    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.

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

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

    Plasminogen activator inhibitor 1

    Measured: 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)

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

    E-selectin

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2015 (estimated)
  2. Study start5 Apr 2016
  3. Primary completion8 Oct 2020
  4. Study completion8 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
213 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02361944
Sponsor's protocol ID
131128
Other IDs
R01GM112871
Acronym
ROCS
Status last verified
Jan 2024
First submitted
30 Jan 2015
Last updated
1 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lopez MG, Pandey AK, Hennessy C, Hughes CG, Absi TS, Shah AS, Shotwell MS, Harrison DG, Billings FT 4th; ROCS Trial Investigators. Effects of Oxygen on Perioperative Vascular Function: A Randomized Clinical Trial. J Am Heart Assoc. 2025 Aug 5;14(15):e041778. doi: 10.1161/JAHA.125.041778. Epub 2025 Jul 17.

    PubMed 40673571
  • Lopez MG, Shotwell MS, Hennessy C, Pretorius M, McIlroy DR, Kimlinger MJ, Mace EH, Absi T, Shah AS, Brown NJ, Billings FT 4th; ROCS trial investigators. Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery: A Randomized Clinical Trial. JAMA Surg. 2024 Oct 1;159(10):1106-1116. doi: 10.1001/jamasurg.2024.2906.

    PubMed 39110454
  • Lopez MG, Pretorius M, Shotwell MS, Deegan R, Eagle SS, Bennett JM, Sileshi B, Liang Y, Gelfand BJ, Kingeter AJ, Siegrist KK, Lombard FW, Richburg TM, Fornero DA, Shaw AD, Hernandez A, Billings FT 4th. The Risk of Oxygen during Cardiac Surgery (ROCS) trial: study protocol for a randomized clinical trial. Trials. 2017 Jun 26;18(1):295. doi: 10.1186/s13063-017-2021-5.

    PubMed 28651648

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Oxygen - normoxia and Oxygen - hyperoxia in people with Cardiac Surgery, run by Vanderbilt University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02361944, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2024.

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