16

17

0.60

Crossover to other surfactant ^c

0.2

3

<0.001

^a Pneumothorax and or pulmonary interstitial emphysema. ^b BPD is bronchopulmonary dysplasia, diagnosed by positive X-ray and oxygen dependence at 28 days. ^c Protocol permitted use of comparator surfactant in patients who failed to respond to therapy with the initial randomized surfactant if the infant was < 72 hours of age, had received a full course of the randomized surfactant, and had an a/A PO₂ ratio < 0.10.

Infasurf versus Survanta® Treatment Trial

A total of 662 infants with RDS who required endotracheal intubation and had an a/A PO₂ < 0.22 were enrolled into a 2 multiple-dose, randomized, double-blind treatment trial comparing Infasurf (4 mL/kg of a formulation that contained 25 mg of phospholipids/mL rather than the 35 mg/mL in the marketed formulation) and Survanta® (4 mL/kg). Repeat doses were allowed ≥ 6 hours following the previous treatment (for up to three doses before 96 hours of age) if the patient required ≥ 30% oxygen. The surfactant was given through a 5 French feeding catheter inserted into the endotracheal tube. The total dose was instilled in four equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5 to 2 minutes. Each of the aliquots was administered with the patient in one of four different positions (prone, supine, right, and left lateral) to facilitate even distribution of the surfactant. Results for the major efficacy parameters evaluated at 28 days or to discharge (incidence of air leaks, death due to respiratory causes or to any cause, BPD, or treatment failure) for all treated patients from this treatment trial were not significantly different between Infasurf and Survanta®.

Prophylaxis Trial

A total of 457 infants £ 30 weeks gestation and < 1251 grams birth weight were enrolled into a multiple-dose, randomized, double-blind trial comparing Infasurf (4 mL/kg of a formulation that contained 25 mg of phospholipids/ mL rather than the 35 mg/mL in the marketed formulation) and Survanta® (4 mL/kg). The initial dose was administered within 15 minutes of birth and repeat doses were allowed ≥ 6 hours following the previous treatment (for up to three doses before 96 hours of age) if the patient required ≥ 30% oxygen. The surfactant was given through a 5 French feeding catheter inserted into the endotracheal tube. The total dose was instilled in four equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5 to 2 minutes. Each of the aliquots was administered with the patient in one of four different positions: prone, supine, right, and left lateral. Results for efficacy endpoints evaluated at 28 days or to discharge for all treated patients from this prophylaxis trial showed an increase in mortality from any cause at 28 days (p=0.03) and in death due to respiratory causes (p=0.005) in Infasurf-treated infants. For evaluable patients (patients who met the protocol-defined entry criteria), mortality from any cause and mortality due to respiratory causes were also higher in the Infasurf group (p=0.07 and 0.03, respectively). However, these observations have not been replicated in other adequate and well-controlled trials and their relevance to the intended population is unknown. All other efficacy outcomes (incidence of RDS, air leaks, BPD, and treatment failure) were not significantly different between Infasurf and Survanta® when analyzed for all treated patients and for evaluable patients.