Inomax (nitric oxide) / Mallinckrodt - LARVOL DELTA

Methemoglobin Concentration in High Dose Inhaled Nitric Oxide (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Jun 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date

iNO300 Therapy in Critically Ill Patients With Pneumonia (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Massachusetts General Hospital | Initiation date: Jun 2025 ➔ Jan 2026 | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial initiation date • Trial primary completion date • Infectious Disease • Pneumonia • Respiratory Diseases

DOMINO: Diffuse Optical Monitoring With Inhaled Nitric Oxide (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Steven Messe | Trial completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Cardiovascular

NORISC: Nitric Oxide for Reduced Intensive Support in Cardiac Surgery With Cardiopulmonary Bypass (clinicaltrials.gov) - P3 | N=3650 | Recruiting | Sponsor: Xijing Hospital | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Cardiovascular • Congestive Heart Failure

Vascular ARDS Recruitment After Inhaled Nitric Oxide (clinicaltrials.gov) - P=N/A | N=70 | Suspended | Sponsor: Massachusetts General Hospital | Trial primary completion date: Apr 2026 ➔ Dec 2028 | Trial completion date: May 2026 ➔ Dec 2028 | Recruiting ➔ Suspended

Trial completion date • Trial primary completion date • Trial suspension • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

iNO300 Therapy in Critically Ill Patients With Pneumonia (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P1 trial • Infectious Disease • Pneumonia • Respiratory Diseases

NORISC: Nitric Oxide for Reduced Intensive Support in Cardiac Surgery With Cardiopulmonary Bypass (clinicaltrials.gov) - P3 | N=3650 | Not yet recruiting | Sponsor: Xijing Hospital | Initiation date: Dec 2024 ➔ May 2025

Adverse events • Trial initiation date • Cardiovascular • Congestive Heart Failure

Mallinckrodt plc Reports Fourth Quarter and Fiscal Year 2024 Financial Results and Provides 2025 Guidance (PRNewswire) - "Acthar Gel net sales were $138.8 million in the fourth quarter, an increase of 33.0% versus the prior year period, and $485.7 million for the full year, an increase of 14.2%...Terlivaz net sales were $6.1 million in the fourth quarter, up from $5.6 million in the same period last year, and $24.7 million for the full year, up from $15.6 million...INOmax (nitric oxide) net sales were $60.8 million in the fourth quarter, down 14.0% compared to the prior year period, and full-year net sales were $261.4 million, down 13.8%, primarily due to competitive pressures in the U.S."

Sales • Ankylosing Spondylitis • Diabetic Nephropathy • Lupus • Multiple Sclerosis • Myositis • Ocular Inflammation • Psoriatic Arthritis • Pulmonary Arterial Hypertension • Renal Disease • Rheumatoid Arthritis • Sarcoidosis • Steven-Johnson Syndrome • Systemic Lupus Erythematosus

Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia (clinicaltrials.gov) - P1/2 | N=32 | Terminated | Sponsor: AdventHealth | N=182 ➔ 32

Enrollment change • Bronchopulmonary Dysplasia • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Effect of INO in Patients with Submassive and Massive PE (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: University of California, Los Angeles | Trial completion date: Jun 2023 ➔ Jun 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Trial completion date • Trial primary completion date • Cardiovascular • Pulmonary Embolism • Respiratory Diseases

Inhaled Nitric Oxide in Severe Obesity (clinicaltrials.gov) - P=N/A | N=60 | Not yet recruiting | Sponsor: Massachusetts General Hospital | Phase classification: P2 ➔ P=N/A

Phase classification • Genetic Disorders • Obesity • Respiratory Diseases • IL10 • IL1B • IL6 • TNFA

NORISC: Nitric Oxide for Reduced Intensive Support in Cardiac Surgery with Cardiopulmonary Bypass (clinicaltrials.gov) - P3 | N=3650 | Not yet recruiting | Sponsor: Xijing Hospital

Adverse events • New P3 trial • Surgery • Cardiovascular • Congestive Heart Failure

An Overview of the INOmax® EVOLVE™ DS Nitric Oxide Delivery System (AARC 2024) - "Sponsored by Mallinckrodt. Presentation to include an overview of the features, patient safety considerations, theory of operation/dual channel design, back-up system, mini-cylinders and alarms of the INOmax EVOLVE DS delivery system."

Respiratory Diseases

A Bench Study of Administering Inhaled Nitric Oxide During Intrapulmonary Percussive Ventilation Superimposed With Invasive Mechanical Ventilation (AARC 2024) - " We compared iNO delivery using three configurations superimposing IPV with the Gentinge Servo-U ventilator, the Percussionaire IPV-2c, and INOmax DSIR Plus in a lung model... The delivery of NO during IPV superimposing with mechanical ventilation was affected by the injector module and IPV adaptor location. The accuracy of NO delivery was within the suggested range when the injector module was followed by the IPV adaptor."

Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Enhancing Working Flow Efficiency with EMR Vent Data Integration (AARC 2024) - "The Servo U, Trilogy 202, EVO EV300 and INOmax DSIR Nitric Oxide are the devices that needed to be integrated into the EMR... On average there was a 42% reduction in time spent entering a ventilator or nitric oxide check. There was a 64% reduction in clicks and an 83% reduction in keystrokes. The reduction in keystrokes significantly reduces the chance for transcription errors."

Respiratory Diseases

Comparison of Noninvasive Inhaled Nitric Oxide Delivery Methods in an Infant Model (AARC 2024) - "The iNO system (INOMax, Mallinckrodt) was set to deliver 5, 20, and 40 ppm... Delivery of iNO with a NIV system was very efficient. Practitioners should be aware that when transitioning to ventilatory support with HFNC a decrease in iNO delivery efficiency may occur. Experimental Set-up"

Respiratory Diseases

Delivered Nitric Oxide With Intrapulmonary Percussive Ventilation: A Bench Study (AARC 2024) - "Two INOMAX DSIR iNO delivery systems were utilized: one injecting and sampling on the dry side of the ventilator circuit and one at the patient y-piece for sampling purposes only, distal to the inflow of the IPV to the ventilator circuit (Figure 1)... IPV treatment inline with the ventilator and iNO impacted iNO delivery and sampling in our bench model. Care should be considered for the change in delivered dose during these concurrent treatments. Further research must be done to understand accurately delivered doses when flow-driven adjunct therapies are required based on patient condition during iNO delivery."

Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Inhaled Nitric Oxide in Severe Obesity (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2 trial • Genetic Disorders • Obesity • Respiratory Diseases • IL10 • IL1B • IL6 • TNFA

Evaluation of Inhaled Nitric Oxide Generation Systems at Altitude. (PubMed, Mil Med) - "Both devices delivered a reliable INO dose at ground level. Altitude significantly affected INO delivery accuracy at 14,000 ft (4,267 meter) (P  0.05) although there were large variations with selected ventilator settings. With careful monitoring, devices creating INO from room air without cylinders could be used during aeromedical transport without the need for pressurized cylinders."

Journal • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia (clinicaltrials.gov) - P1/2 | N=182 | Terminated | Sponsor: AdventHealth | Trial completion date: Dec 2024 ➔ Oct 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Oct 2023; based on DSMB recommendation at interim analysis

Trial completion date • Trial primary completion date • Trial termination • Bronchopulmonary Dysplasia • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia (clinicaltrials.gov) - P1/2 | N=182 | Active, not recruiting | Sponsor: AdventHealth | Recruiting ➔ Active, not recruiting | N=138 ➔ 182

Enrollment change • Enrollment closed • Bronchopulmonary Dysplasia • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Methemoglobin Concentration in High Dose Inhaled Nitric Oxide (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed

iNO: Inhaled Nitric Oxide in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: Wake Forest University Health Sciences | Trial completion date: Apr 2025 ➔ Jul 2025 | Trial primary completion date: Nov 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date • Cardiovascular • CNS Disorders • Ischemic stroke • Vascular Neurology

Vascular ARDS Recruitment After Inhaled Nitric Oxide (clinicaltrials.gov) - P=N/A | N=70 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL10 • IL6 • TNFA • VEGFA

Inhaled Nitric Oxide for ARDS-related Pulmonary Hypertension (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Yuri Matusov

New P1 trial • Acute Respiratory Distress Syndrome • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases