Nitric Oxide for Cardiac Surgery

(NORISC Trial)

Recruiting at 3 trial locations

Overseen By ziyu Zheng, ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Xijing Hospital

Must not be taking: Inhaled nitric oxide, Prostacyclin

Disqualifiers: Emergency surgery, Heart failure, Kidney disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 hours post-ICU admission or until extubation

3650 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if inhaled nitric oxide can reduce complications after heart surgery involving a machine that maintains blood and oxygen flow. The focus is on minimizing serious issues such as heart failure, kidney problems, respiratory failure, and other major adverse events within 30 days post-surgery. Participants will receive either nitric oxide or standard care during and after surgery. Individuals undergoing planned heart or aortic surgery requiring a heart-lung machine, who have not had previous heart surgery, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment nearing widespread availability.

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.

Is there any evidence suggesting that inhaled nitric oxide is likely to be safe for humans?

Research has shown that inhaled nitric oxide (iNO) is generally safe for patients undergoing heart surgery. Earlier studies demonstrated that iNO improved blood flow and oxygen levels in patients with pulmonary hypertension during surgery. This treatment did not increase the need for blood or platelet transfusions, indicating good tolerance.

Early data also suggest that iNO can reduce signs of organ injury and complications in patients using a heart-lung machine during heart surgery. Other reports indicated that all patients who received iNO treatment were successfully discharged, and the treatment did not affect ventilator settings.

While these findings are encouraging, larger studies are still needed to confirm these benefits and ensure the treatment's safety for a broader patient population. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for heart conditions during surgery focus on maintaining blood flow and protecting the heart with medications like beta-blockers or calcium channel blockers. However, Nitric Oxide (NO) is unique because it targets the blood vessels directly, helping them widen and improve blood flow. Unlike standard treatments, NO is administered through inhalation during and after cardiopulmonary bypass, which could enhance oxygen delivery and reduce complications. Researchers are excited about this approach because it could lead to faster recovery times and better outcomes for patients undergoing heart surgery.

What evidence suggests that inhaled nitric oxide might be an effective treatment for cardiac surgery complications?

This trial will compare inhaled nitric oxide (iNO) with standard care in patients undergoing cardiac surgery. Research has shown that iNO can reduce the time patients spend on breathing machines after heart surgery and decrease certain indicators of organ damage and complications. This suggests it might improve heart and lung function post-surgery. However, previous studies did not find that iNO affected ICU or hospital stay durations, or survival rates. The main issue has been the small size of earlier studies, which makes it difficult to confirm its full benefits. Larger studies are needed to validate these findings. ^{2 3 6 7 8}

Who Is on the Research Team?

Chong Lei, M.D., & phd

Principal Investigator

Xijing Hospital

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Intervention: iNO Group Experimental Treatment 1 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 Group Placebo Group 1 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.

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+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of nitric oxide in cardiac surgery. Nonami, Y.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38556145/

Inhaled nitric oxide and postoperative outcomes in cardiac ... The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1089860324000417

Inhaled nitric oxide and postoperative outcomes in cardiac ... The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06702553?term=show%20wu%20pain&viewType=Table&checkSpell=&rank=9

Nitric Oxide for Reduced Intensive Support in Cardiac ... Preliminary data support the effect of inhaled NO on reducing biomarkers of organ injury and clinical signs of organ dysfunction in cardiac surgery under CPB.

4. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4142086

Abstract 4142086: Efficacy And Safety Of Inhaled Nitric ... Our analysis showed that iNO significantly reduced the duration of mechanical ventilation (MD = -5.733, 95% CI [-10.494; -0.972]). However, no ...

5. annalsthoracicsurgery.org annalsthoracicsurgery.org/article/S0003-4975(01)03398-7/fulltext

Beneficial effects of inhaled nitric oxide in adult cardiac ... Inhaled nitric oxide effectively and selectively lowered right ventricular afterload and right ventricular work in critically ill adult cardiac patients.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37713058/

Real-world safety and effectiveness of inhaled nitric oxide ... INOflo treatment was a safe and effective strategy to improve hemodynamics and oxygenation in patients with pulmonary hypertension during cardiac surgery.

7. link.springer.com link.springer.com/article/10.1007/s11748-023-01971-2

Real-world safety and effectiveness of inhaled nitric oxide ... INOflo treatment was a safe and effective strategy to improve hemodynamics and oxygenation in patients with pulmonary hypertension during cardiac surgery.

8. bmccardiovascdisord.biomedcentral.com bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-025-04967-3

Innovative nitric oxide delivery technology for postoperative ... All patients received iNO treatment successfully and were discharged. The NO concentration remained stable, unaffected by ventilator settings, ...