3650 Participants Needed

Nitric Oxide for Cardiac Surgery

(NORISC Trial)

Recruiting at 2 trial locations
CL
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zZ
Overseen Byziyu Zheng, ph.D.
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are already on inhaled nitric oxide therapy or inhaled/aerosolized prostacyclin, you cannot participate in the trial.

What data supports the effectiveness of the treatment Nitric Oxide for cardiac surgery?

Research suggests that nitric oxide can protect organs during cardiac surgery, especially the heart and kidneys, and may improve outcomes by acting as a safe and promising approach in managing patients during surgery. It has also shown benefits in improving oxygen levels in patients after heart surgery, potentially reducing complications and hospital stay.12345

Is nitric oxide safe for use in cardiac surgery?

Nitric oxide is considered safe for use in cardiac surgery, with side effects that are known, predictable, reversible, and relatively rare. It has been used in clinical practice at an acceptable cost, and further research supports its safety and potential benefits in managing patients during surgery.13567

How does the drug nitric oxide differ from other treatments for cardiac surgery?

Nitric oxide is unique in cardiac surgery because it acts as a protective agent for organs and tissues during the operation, especially benefiting the heart and kidneys. Unlike other treatments, it can be administered to supplement the body's own nitric oxide production, which may be reduced during surgery, and it is known for its predictable and reversible side effects.14589

What is the purpose of this trial?

Cardiac surgery is a procedure that is commonly performed worldwide. Despite these technological advances, cardiac surgery remains a high-risk surgery. Among post-operative complications, acute kidney injury, respiratory failure, myocardial infarction, and stroke as well as cognitive dysfunction are significant causes of mortality in patients undergoing and following cardiac surgery. Inhaled nitric oxide (NO) therapy as a selective pulmonary vasodilator in cardiac surgery has been one of the most significant pharmacological advances in managing pulmonary hemodynamics and life threatening right ventricular dysfunction and failure. In addition, newer applications show greater promise of inhaled NO as a therapy in the area of cardiac surgery associated acute kidney injury and ischemia reperfusion. However, this remarkable expectation to inhaled NO has experienced a roller-coaster ride with high hopes and nearly universal demonstration of physiological benefits but disappointing translation of these benefits to harder clinical outcomes, like mortality. Most of our understanding on the iNO field in cardiac surgery stems from small observational or single center randomized trials, which failed to ascertain strong evidence base. As a consequence, there are only week clinical practice guidelines on the field and only European expert opinion for the use of iNO in routine and more specialized cardiac surgery. There is need for a large multicenter randomized controlled study to confirm the administration of iNO as an effective weapon for the battle against life threatening complication in high risk cardiac surgical patients.In a previous meta analysis with 27 studies included, we demonstrated that inhaled nitric oxide (NO) could reduce the duration of mechanical ventilation and reducing biomarkers of organ injury and clinical signs of organ dysfunction in cardiac surgery under cardiopulmonary bypass (CPB) , but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies (of the 27 studies included, 20 studies with sample size less than 100) and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.We are planning a large multicenter controlled randomized trial to demonstrate that inhaled nitric oxide can reduce composite outcome of death and Major Adverse Events (MAEs), including need for intensive supports due to heart failure, low cardiac output sydrome, or renal failure, respiratory failure, etc., and myocardial infarction, stroke, and sepsis at 30 days after surgery from 20% to 16% in patient undergoing cardiac surgery with cardiopulmonary bypass.If the hypothesis had been proved and validated, the results of this study can provide strong evidence for guidelines to facilitate the routine use of iNO in all cardiopulmonary bypass assisted cardiac procedures with 31,800 postoperative outcomes improved per year in US and in China.

Research Team

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Chong Lei, M.D., & phd

Principal Investigator

Xijing Hospital

Eligibility Criteria

This trial is for adults (18+) needing elective cardiac or aortic surgery with cardiopulmonary bypass. It's not open to those who've had previous open-heart surgeries.

Inclusion Criteria

I am scheduled for heart or aortic surgery that needs a heart-lung machine.
I have never had open heart surgery.

Exclusion Criteria

I need heart surgery that involves cooling my body and stopping my blood circulation.
I am scheduled for heart surgery to fix a birth defect.
I am scheduled for a heart transplant.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive inhaled nitric oxide during cardiopulmonary bypass and postoperatively to reduce major adverse events

6 hours post-ICU admission or until extubation
In-hospital treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of major adverse events and mortality

30 days
Regular follow-up visits

Extended Follow-up

Long-term monitoring of mortality and quality of life outcomes

1 year

Treatment Details

Interventions

  • Nitric Oxide
Trial Overview The study tests if inhaling nitric oxide gas can reduce death and major complications like heart failure, kidney failure, respiratory issues, etc., within 30 days after surgery compared to standard care.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Intervention: iNO GroupExperimental Treatment1 Intervention
Patients will receive 80 parts per million (ppm) NO during CPB through the oxygenator. After weaning of CPB, test gases will be delivered via inspiration limb of ventilator at a dose range of 40-80 ppm until 6 hours after ICU admission or until extubation after surgery, whichever comes first.
Group II: Standard Care/Control GroupPlacebo Group1 Intervention
Patients in this group will receive standard care and 80 ppm nitrogen (N2, control group) are added to the gas mixture as control. In the circumstances when the N2 is not applicable, such as when the plasma-chemical NO synthesis device is employed for NO generatiaon and delivery, the device will be connected to the CPB and ventilator circuits, but the synthesis will remain inactive in the control group. Consequently, the circuit will be supplied with air devoid of NO.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Xijing Hospital

Lead Sponsor

Trials
442
Recruited
1,300,000+

Tomsk National Research Medical Center of the Russian Academy of Sciences

Collaborator

Trials
64
Recruited
110,000+

Massachusetts General Hospital

Collaborator

Trials
3,066
Recruited
13,430,000+

Tianjin Chest Hospital, Tianjin, China

Collaborator

Trials
1
Recruited
3,700+

NORISC Trial Investigators

Collaborator

Trials
1
Recruited
3,700+

Nikolay O. Kamenshchikov., M.D., Tomsk National Research Medical Center of the Russian Academy of Sciences

Collaborator

Trials
1
Recruited
3,700+

Jiange Han, Tianjin Chest Hospital, Tianjin, China

Collaborator

Trials
1
Recruited
3,700+

Qingping Wu, Wuhan Union Hospital, Wuhan, China

Collaborator

Trials
1
Recruited
3,700+

Evgeniy Grigoriev, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation

Collaborator

Trials
1
Recruited
3,700+

Vladimir Boboshko, E. Meshalkin National Medical Research Center, Novosibirsk, Russian Federation

Collaborator

Trials
1
Recruited
3,700+

Findings from Research

Nitric oxide (NO) has a complex role in cardiac health, showing both cardioprotective effects during myocardial ischemia-reperfusion and potential to worsen reperfusion injury by producing harmful peroxynitrite.
Exogenous supplementation of NO, particularly through agents like protamine sulfate, may enhance NO production and provide therapeutic benefits in conditions like pulmonary hypertension and atherosclerotic coronary heart disease.
The role of nitric oxide in cardiac surgery.Nonami, Y.[2022]

References

Nitric Oxide in Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials. [2019]
Effects of inhaled nitric oxide on respiratory system mechanics, hemodynamics, and gas exchange after cardiac surgery. [2019]
Beneficial effects of inhaled nitric oxide in hypoxaemic patients after coronary artery bypass surgery. [2019]
The role of nitric oxide in cardiac surgery. [2022]
Nitric Oxide in Cardiac Surgery: A Review Article. [2023]
Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial. [2020]
Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial. [2018]
8.Russia (Federation)pubmed.ncbi.nlm.nih.gov
[The peculiarties of nitric oxide synthesis in patients after coronary bypass surgery]. [2015]
A potential role for nitric oxide in myocardial stunning. [2019]
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