Effect of Nitric Oxide in Cardiac Surgery Patients With Endothelial Dysfunction. (MGHK23)
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02836899|
Recruitment Status : Recruiting
First Posted : July 19, 2016
Last Update Posted : August 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Kidney Injury||Drug: Nitric Oxide Other: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||250 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Prevention of Acute Kidney Injury by Nitric Oxide in Prolonged Cardiopulmonary Bypass. A Double Blind Controlled Randomized Trial in Cardiac Surgical Patients With Endothelial Dysfunction.|
|Actual Study Start Date :||February 8, 2017|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2021|
Placebo Comparator: Control
Inhaled nitrogen will be administered via the cardiopulmonary bypass (CPB) machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the Intensive Care Unit (ICU). Once patients are extubated they will breathe test gas via a facemask or nasal cannula. Test gas administration will commence at the onset of CPB and last for 24 hours.
This is the placebo group. Nitrogen will be added instead of nitric oxide.
Experimental: Nitric Oxide
Inhaled nitric oxide (iNO) will be administered via the CPB machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the ICU. Once patients are extubated they will breathe test gas via a facemask or nasal cannula. Test gas administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, iNO will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.
Drug: Nitric Oxide
Inhaled nitric oxide will be administered in a final concentration of 80 ppm. The treatment will begin at the onset of the cardiopulmonary bypass until to 24h after Intensive Care Unit (ICU) admission, including 2-4 hours of weaning from nitric oxide and careful hemodynamics monitoring.
- Acute kidney injury [ Time Frame: 7 days ]Incidence of Acute Kidney injury according to KDIGO criteria.
- AKI severity [ Time Frame: 7 days after cardiac surgery ]Difference in AKI severity between the two groups using following KDIGO stages.
- Renal replacement therapy [ Time Frame: up to 1 year ]To study the incidence of acute renal failure requiring RRT
- Major Adverse Kidney Events (MAKE) [ Time Frame: 6 weeks after cardiac surgery ]Difference between groups of MAKE at 6 weeks after surgery. MAKE is a composite outcome of death, new dialysis and worsened renal function (defined as a 25% or greater decline in eGFR compared to the baseline).
- Organ dysfunction [ Time Frame: 7 days ]Assessment of organ dysfunction through the evaluation of SOFA score
- Prolonged cardiovascular support [ Time Frame: 48 hours after cardiac surgery ]Difference between groups of prolonged cardiovascular support defined as need for vasopressors, inotropic agents, balloon pump, or ventricular-assist device for more than 48 hours after cardiac surgery.
- Vasoactive-inotropic score (VIS) [ Time Frame: 7 days after cardiac surgery ]Difference between groups of maximum daily VIS and duration of vasopressors and or inotropic agents support. VIS is calculated as Dopamine dose (mcg/kg/min) + Dobutamine dose (mcg/kg/min) + 100 x Epinephrine dose (mcg/kg/min) + 10 x Milrinone dose (mcg/kg/min) + 10,000 x Vasopressin dose (units/kg/min) + 100 x Norepinephrine dose (mcg/kg/min) + 10 x Phenilephrine dose (mcg/kg/min).
- Duration of mechanical ventilation [ Time Frame: up to 6 weeks ]Difference of duration of mechanical ventilation
- Intensive care unit length of stay (ICU-LOS) [ Time Frame: up to 6 weeks ]Difference between groups of ICU-LOS defined as number of days spent in an ICU bed.
- Hospital length of stay (LOS) [ Time Frame: up to 1 year ]Difference between groups of hospital LOS defined as number of days spent in a hospital bed.
- Renal tubular injury [ Time Frame: Up to 6 weeks ]Renal biomarkers to evaluate renal tubular injury.
- Incidence of AKI related to risk factors [ Time Frame: 7 days ]Incidence and severity of AKI related to presence of CKD at baseline, duration of CPB, duration of aortic cross clamp, levels of free Hb, levels of NO consumption, pulmonary pressure at baseline, cardiovascular risks associated with endothelial dysfunction, scheduled procedure and EuroSCORE II.
- Incidence of delirium [ Time Frame: 7 days after cardiac surgery ]Difference between groups of Incidence of Delirium will be assessed daily in the first 7 days after surgery by using the confusion assessment method for intensive care unit (CAM-ICU).
- Score of the Activity of Daily Living [ Time Frame: One year follow up ]Analysis of the quality of life up to 1 year after surgery by the Activity of Daily Living evaluation (by Katz Index) and PROMIS global health.
- Overall mortality [ Time Frame: up to 1 year ]Evaluation of the overall intrahospital mortality and at 28 6 weeks 90 days and 1 year after surgery
- Methemoglobin levels in blood [ Time Frame: During and 48 hours after cardiac surgery ]Blood methemoglobin levels will be measured to evaluate the oxidation of oxyhemoglobin in the two groups until 48h after surgery.
- Incidence of non fatal stroke [ Time Frame: 6 weeks ]Difference between groups of incidence of non fatal stroke will be assessed by at 6 weeks after cardiac surgery.
- Perioperative and non-perioperative nonfatal myocardial infarction [ Time Frame: 72 hours and 1 year follow up ]Incidence of Perioperative and non-perioperative nonfatal myocardial infarction as defined by the third universal definition of MI released in 2012 by the ESC/ACCF/AHA/WHF.
- Post operative bleeding [ Time Frame: 24 after surgery ]Incidence of postoperative bleeding calculated as the sum of blood loss through thoracic drains from the moment of closure of the chest over a period of 24 hours.
- Transfusions [ Time Frame: 7 days surgery ]Differences between the two groups of transfusions with plasma and stored or autologous red blood cells (RBCs) recovered using intraoperative cell salvage devices.
- Post-operative infections [ Time Frame: 6 weeks ]Post-operative infections (e.g., pneumonia, wound infection, endocarditis, central line infection, urinary tract infection, sepsis).
- Cardiac and non-cardiac complications [ Time Frame: 6 weeks ]Cardiac arrhythmias and other non-cardiac post-operative complications (e.g., hepatobiliary disorders, pneumothorax, pleural effusion, vascular disorders).
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): NCT02836899
|Contact: Lorenzo Berra, MD||+1 (617) 643 7733||LBERRA@mgh.harvard.edu|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Lorenzo Berra, MD 617-643-7733 email@example.com|
|Principal Investigator:||Lorenzo Berra, MD||Massachusetts General Hospital|