We plan to conduct a large, prospective, randomized trial of early non-tidal (high frequency oscillatory ventilation, HFOV) vs tidal(synchronized intermittent mandatory ventilation with continuous tidal volume monitoring, SIMV) ventilation in infants ≤1200 g. For a large multicenter trial to be successful, strict compliance with the study protocol is essential. We performed a pilot study of 50 infants from 7 centers to test the feasibility of the study protocol in a variety of geographically diverse ICNs, including both university-based and community-based nurseries. Eligible infants were <4 hrs old, had received 1 dose of Survanta, and were ventilated with mean airway pressure (paw)≥6 cm H2O and FiO2>0.25. Infants were stratified by BW (501-800, 801-1200g) and maternal steroid status, and randomized to HFOV or SIMV. HFOV was provided by the SensorMedics 3100A, and SIMV by VIP Bird or Drager ventilators. The protocol dictated changes of ventilator settings in response to oxygenation (pulse oximetry), ventilation (PaCO2), measured tidal volume (SIMV patients), and lung inflation(chest radiographs). In both HFOV and SIMV arms, a strategy of modest permissive hypercapnia (PaCO2 40-55 torr) and “normal” lung inflation (dome of right hemidiaphragm between 8 and 9.5 ribs) was used. The protocols were designed to aggressively wean patients to extubation. Regular decreases in ventilator support were mandated for patients who were within the target SaO2, PaCO2, and lung inflation ranges for >12 hrs. Extubation was mandated for any patient with FiO2 ≤0.25; and mean Paw ≤5 cmH2O (SIMV) or ≤7 cmH2O (HFOV). All patients were treated with xanthines prior to extubation, and were placed on the Aladdin NCPAP when extubated. Protocols also included use of: a) prophylactic indomethacin, b) Survanta, and c) steroids for any patient ventilated with FiO2 > 0.30 at ≥10 days. 26 HFOV patients (BW 823 ± 215 {SD} g, age at entry 2.8 ± 1.2 hrs); and 24 SIMV patients (BW 856 ± 206 g, age at entry 2.3 ± 1.1 hrs) were entered. Protocol compliance was graded by dividing each patient's ventilator course into sequential 6 hr epochs. Percent of epochs in which the protocol was followed was then calculated for each patient. Protocol compliance was 88% for HFOV and 82% for SIMV patients (P=0.17). We conclude that these protocols, which address all aspects of ventilator management in patients <1200 gms on HFOV and SIMV, 1) can be implemented in a variety of settings, and 2) are easily followed with an acceptable degree of compliance. These protocols will be used in the planned large multicenter trial.