drugset / Trial / NCT06702553

Nitric Oxide for Reduced Intensive Support in Cardiac Surgery With Cardiopulmonary Bypass

Phase 3 Recruiting 3650 enrolled Xijing Hospital Andrei Bautin, The Almazov National Medical Research Centre, St. Petersburg, Russian Federation · collab Evgeniy Grigoriev, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation · collab Evgeniy Rosseykin, Federal Center of Cardiovascular Surgery, Khabarovsk, Russian Federation · collab Grigoryev Evgeny, Scientific Research Insitute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia. · collab Jia Min, The First Affiliated Hospital of Nanchang University, Nanchang, China. · collab Jiange Han, Tianjin Chest Hospital, Tianjin, China · collab Jiawan Wang, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China · collab Jing Shi, The Afffliated Hospital of Guizhou Medical University, Guiyang, China. · collab Lorenzo Berra., M.D., Massachusetts General Hospital · collab Mikhail Vasilev, Meshalkin National Medical Research Center, Мeshalkin of the ministry of health of the Russian Federation,Novosibirsk,Russia. · collab Nikolay O. Kamenshchikov., M.D., Tomsk National Research Medical Center of the Russian Academy of Sciences · collab Qingping Wu, Wuhan Union Hospital, Wuhan, China · collab Vladimir Boboshko, E. Meshalkin National Medical Research Center, Novosibirsk, Russian Federation · collab Vladimir Pichugin, Specialized Cardiac Surgery Clinical Hospital named after Academician B.A. Korolev, Nizhny Novgorod, Russian Federation · collab Zongbin Song, Xiangya Hospital, Central South University, Changsha, China. · collab

RandomizedParallel-groupQuadruple-blindTreatment

Summary

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.

Timeline

Start: 2025-05-19
Primary completion: 2028-03-31
Completion: 2029-03-31

Publications

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Nitric Oxide	Other / unclassified	40 ppm	Inhaled
Subject	Nitric Oxide	Other / unclassified	80 ppm	Inhaled

Indications

No indication recorded.