PROSPECTIVE STUDY OF NITRIC OXIDE FOR SICKLE CELL PAIN CRISIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The study is an investigator-initiated and industry/intramural NIH sponsored trial involving a collaborative research and development agreement between NIH and INO Therapeutics. The goal is to determine the safety and efficacy of nitric oxide (NO) for inhalation in the treatment of vaso-occlusive pain crisis (VOC) in patients with sickle cell disease. It is a prospective, multicenter, double-blind, randomized, placebo-controlled trial sponsored by INO Therapeutics with the study initiated by the PI, Dr. Mark Gladwin from the NIH Clinical Center. Nationally, 142 subjects are expected to enroll over an 18 month period. Locally 20 subjects will be enrolled. The study population is comprised of persons with SS or S-Beta-thalassemia who present with VOC. 80 ppm inhaled NO will be given by face mask using a blinded version of the INOvent continuous flow, delivery system for 4 hours then 40 ppm for another 4 hours. It will be delivered with air and oxygen to an FIO2 of 24%. If required, patients in the NO group who remain in the hospital will continue to receive 800 ppm NO by inhalation at 6 mL/pulse/breath via nasal cannula using the INOpulse, pulsed flow, delivery system, for up to 72 hours total treatment time with 1 liter continuous oxygen if 60 pounds (27kg) or greater or 3 ml/pulse/breath if less than 60 pounds. Placebo is 100% grade 5 nitrogen gas delivered with oxygen at 24% by continuous flow for 8 hours. Patients who remain in the hospital will continue to receive it by nasal cannula at 6ml/pulse/breath at 800 ppm using the INO pulse delivery system with 1 liter continuous oxygen if 60 pounds or greater and 3 mL/pulse/breath if less than 60 pounds up to 72 hours total. Primary efficacy is time to resolution of VOC. Safety endpoints are incidence and types of reported SAE and proportion of patients withdrawn from study for safety issues. Primary analysis is a Wilcoxon ranked sum test or in case of censored times to crisis resolution the Gehan-Wilcoxon test to compare the difference in median duration of VOC.