The NIH was one of eleven centers nationwide in this prospective, multi-center, double-blind, randomized, placebo-controlled study of 150 patients with SCD presenting with vaso-occlusive pain crisis. The objective was to determine the safety and efficacy of nitric oxide for inhalation in the treatment of vaso-occlusive pain crisis in patients with sickle cell disease and to validate an approved device for transcutaneous measurement of methemoglobin in a population of patients with sickle cell anemia.. The study population included patients with sickle cell disease (SS, S-beta-Thalassemia) presenting with vaso-occlusive pain crisis. Patients with known SCD were identified and consented prior to their presentation to the Emergency Department/Emergency Clinic (ED/EC) or other appropriate unit. Entry into the trial began when the patient presented to the ED/EC or other appropriate unit in pain crisis, met all inclusion criteria and signed an informed consent confirming their willingness to participate. Participants were 10 years of age or above and were administred either placebo or inhaled nitric oxide to see if the experimental agent, inhaled nitric oxide, could reduce the time it takes for resolution of the vaso-occlusive crisis. We, at the NIH, began pre-enrolling in January 2005 and pre-enrolled 116 subjects. Of these 116 subjects, 51 actually enrolled and were randomized to either placebo or nitric oxide and an additional 13 more subjects who were not pre-enrolled also were randomized in the study, bringing the total number of subjects at the NIH randomized to the study to 64. Of these 64 subjects, 5 were children. Some of the other participating sites also pre-enrolled subjects. The total number of subjects randomized in the treatment study was 150. As of December 22, 2008 the protocol was closed to recruitment and enrollment. The trial lasted for approximately 45 months and all participating sites have completed enrollment and follow up. The study remains open for data analysis and manuscript preparation. Preliminarily, the primary outcome measure is negative. Subjects treated with inhaled nitric oxide did not have a shorter duration of crisis than those treated with placebo. Additional analysis of secondary outcome variables is proceeding.
|Gladwin, Mark T; Kato, Gregory J; Weiner, Debra et al. (2011) Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA 305:893-902|