Randomized, Placebo-controlled Trial of Inhaled Treprostinil for Patients at Risk for Acute Respiratory Distress Syndrome.

RATIONALE Inhaled treprostinil may improve oxygenation and have additional antiinflammatory effects in early acute hypoxemic respiratory failure, potentially preventing or reducing severity of Acute Respiratory Distress Syndrome (ARDS). OBJECTIVE To determine whether administration of inhaled treprostinil to patients at risk for ARDS is feasible, safe, and efficacious. METHODS We performed a double-blind, placebo-controlled, single-center randomized pilot trial at a quaternary care academic medical center. Patients with acute hypoxemia due to pneumonia or signs of low-pressure pulmonary edema with a unilateral or bilateral infiltrate on chest imaging and a ≥ 4 liter per minute supplemental oxygen requirement but not requiring positive pressure ventilation were evaluated. Randomized patients received study drug or placebo (2:1 ratio respectively). Treatment was initiated at 6 breaths every four hours and titrated up to 12 breaths. Subjects were maintained on treatment for 7 days, and then tapered off over a period of 4 days. Study drug was stopped if positive pressure ventilation was required (invasive or non-invasive). RESULTS Fourteen patients were enrolled over a period of 31 months. Baseline characteristics were not significantly different between treatment groups with respect to age, gender, race, APACHE score, LIPS score or baseline mean SaO2/FiO2 ratio. Trends in daily baseline and 30- minute post-dose SaO2/FiO2 ratio for all treatment points were not significantly different between placebo and treprostinil. Four patients required positive pressure ventilation in the treprostinil group vs one in the placebo group. CONCLUSIONS Inhaled treprostinil administration is feasible in patients at risk for ARDS, but was not associated with improvement in the S/F ratio relative to placebo. Drug-associated adverse events were not severe nor unexpected based on the known adverse effect profile of inhaled treprostinil. The clinical benefit of this intervention is unclear at this time in the absence of larger studies. Clinical trial registered with Clinicaltrials.gov (NCT02370095).