Evaluation of Inhaled Nitric Oxide on Right Ventricular Function and Pulmonary Vascular Mechanics Post-Cardiac Surgery

The primary objective of this study is to investigate the effects of **inhaled nitric oxide (iNO)** on pulmonary vascular mechanics, right ventricular function, and right ventricular-vascular coupling in patients during the immediate post-operative period following cardiac surgery. This is clinically relevant as optimizing right ventricular function and pulmonary vascular mechanics can significantly impact patient recovery and outcomes after cardiac surgery.

Secondary objectives include:

• Evaluating the synergistic effects of iNO combined with a lung recruitment maneuver on pulmonary vascular mechanics, right ventricular function, and right ventricular-vascular coupling in the immediate post-operative period after cardiac surgery.
• Studying patterns of pulmonary blood flow redistribution, measured by electrical impedance tomography (EIT), that predict a positive effect on vascular mechanics and right ventricular function.

The clinical trial involves **patients** in the immediate cardiac surgery post-operative period, focusing on the effects of inhaled iNO on pulmonary vascular mechanics, right ventricular function, and right ventricular-vascular coupling. The study population includes both male and female participants, aged over 18 years, who are under passive mechanical ventilation. Participants are required to have a pre-operative FEVI of at least 30%, absence of hypovolemia, stable spontaneous heart rhythm, and post-operative hemodynamic stability. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria emphasize informed consent and specific health conditions, ensuring a targeted and relevant study group.

The clinical trial is designed to evaluate the effects of **inhaled nitric oxide** on pulmonary vascular mechanics and right ventricular function in patients during the immediate post-operative period following cardiac surgery. This is a Phase III, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on January 24, 2025, and conclude by December 31, 2027. Participants will be randomly assigned to receive either the investigational product, **VasoKINOX 800 ppm mol/mol**, or a control treatment. The investigational product is administered as a **medicinal gas, compressed** via inhalation.

The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be assessed based on criteria such as age over 18 years, being under passive mechanical ventilation, and post-operative hemodynamic stability. Participants must provide informed consent and meet all inclusion criteria to be enrolled. Follow-up visits will monitor parameters of right ventricular function and secondary endpoints, including the results of electrical impedance tomography. The end-of-study visit will evaluate the overall outcomes and safety of the treatment.

Participant involvement is expected to last for a maximum of one day, corresponding to the **max treatment period** of the investigational product. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any situation that compromises the participant's safety. The primary endpoint focuses on parameters of right ventricular function, while secondary endpoints include the regional distribution of ventilation and perfusion as assessed by electrical impedance tomography. The trial aims to provide valuable insights into the therapeutic potential of **inhaled nitric oxide** in the specified patient population.

The clinical trial involves the administration of **VasoKINOX 800 ppm mol/mol**, a **medicinal gas, compressed** formulation containing **nitric oxide** as the active substance. This experimental medication is provided by AIR LIQUIDE SANTE INTERNATIONAL and is identified by the marketing authorization number 82148. The pharmaceutical form is a compressed gas intended for inhalation. The administration route is via **inhalation gas**, with a maximum daily dose of 40 parts per million (ppm) and a total maximum dose of 40 ppm. The treatment period is limited to a maximum of one day. The trial aims to evaluate the effects of inhaled nitric oxide on pulmonary vascular mechanics and right ventricular function following cardiac surgery.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. The focus remains solely on the administration of the experimental medicinal gas. Participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed inhalation regimen. The trial does not involve any pediatric formulations or orphan drug designations. The study is conducted under the authorization of the relevant regulatory bodies, ensuring compliance with clinical trial standards and protocols.

Efficacy in the clinical trial titled "Role of inhaled nitric oxide on right ventricular function and pulmonary vascular mechanics following cardiac surgery" will be assessed using specific primary and secondary endpoints. The primary endpoint focuses on evaluating the **right ventricular function** parameters. This will provide insights into the effects of inhaled nitric oxide (iNO) on the heart's ability to pump blood effectively post-cardiac surgery. Secondary endpoints include the results of electrical impedance tomography (EIT), which will assess the regional distribution of ventilation and perfusion, as well as EIT pulsatility. These measurements will help determine the impact of iNO on pulmonary vascular mechanics and right ventricular-vascular coupling.