Inhaled carbon monoxide (CO) delivered in small doses to patients on mechanical ventilation is being tested as a novel therapy to accelerate the resolution of acute respiratory distress syndrome (ARDS) because, apart from lung protective ventilation, no effective interventions exist for ARDS.

A team of Duke lung specialists is working with colleagues at 3 US hospitals to study a CO dosage and delivery system (NCT02425579). The study’s objective is to assess the safety of inhaled CO therapy in patients on mechanical ventilation with sepsis-induced ARDS. The other participating organizations are Weill Medical College of Cornell University (sponsor) in New York and Massachusetts General Hospital and Brigham and Women’s Hospital in Boston. The team of investigators plans to begin phase 2 in 2017.

Bryan D. Kraft, MD, a Duke critical care specialist and pulmonologist, says regular rounding in the intensive care unit to assess patients with ARDS prompted the initiative.

“Supportive care is all we can provide,” says Kraft, who is the study’s coinvestigator. “Sometimes it’s enough, but in many cases, the lungs never heal and the patients become ventilator-dependent. These challenging cases led us to propose new strategies for patients with ARDS by trying to jumpstart healing rather than waiting for the lung to heal by itself.”

Kraft is working with Claude A. Piantodosi, MD, interim chief of the Duke Division of Pulmonary, Allergy, and Critical Care Medicine, and Karen E. Welty-Wolf, MD, pulmonologist at the Durham Veterans Affairs Medical Center and co–principal investigator. The Duke team has worked for many years on adjunctive therapies for ARDS, particularly in connection with sepsis and pneumonia.

The study team has partnered with 12th Man Technologies in Los Angeles to create a portable sensing and dosing device approximately the size of a toaster that is in line with the ventilator circuit.

“The device measures the patient’s respiratory rate and tidal volume, as well as the delivered CO concentration, hundreds of times per second and adjusts the CO dosing to maintain a constant concentration,” Kraft says.

For nearly 2 decades, Kraft says, researchers have recognized the potential benefits of CO as a treatment for acute lung injury and ARDS, despite its known toxicity at high concentrations. In a previous study involving nonhuman primates, Kraft’s team demonstrated the therapeutic potential of using small doses of CO delivered via this ventilator-compatible delivery system.

“Our objective was to take this experimental therapy for ARDS from a preclinical setting to a clinical setting in 5 years,” Kraft says. “We accomplished that. Now our goal is to show it is safe in critically ill patients and to move to a phase 2 and ultimately phase 3 clinical trial.”