Randomized Phase III Trial Assessing Regional Lung Function for Lung Transplant by Hyperpolarized 129Xenon Gas MRI

Hyperpolarized 129Xe (HPX) MRI is a promising diagnostic modality with the potential to move beyond structural imaging by CT, overcome the lack of regionality of pulmonary function testing, and improve spatial resolution compared to 133Xenon Scintigraphy (XS). As part of an FDA registration program, we conducted a phase III multicenter trial in patients undergoing lung transplant evaluation to establish the equivalence of HPX to evaluate regional pulmonary function with the currently approved standard, XS. Subjects were randomized to undergo either HPX followed by XS or XS followed by HPX. 129Xe was hyperpolarized by the Polarean HPX system. Ventilation of the six (6) lung zones was quantified to determine the contribution of each zone to total lung function, and then used to calculate the fraction of ventilation contributed by each zone. The primary endpoint would be met if the 95% confidence interval (CI) of the mean intra-patient differences between the modalities fell within the prospectively defined equivalence margin of ±14.7%. 49 subjects (15 females, age 61.5±10.5, O2 3.6±1.3 liter/min) were enrolled and received HPX and XS. HPX was well tolerated. The intra-patient mean difference of the ventilation measured by HPX vs XS was -1.59 ±7.28% (95%CI -3.69-0.50%). The 95% CI for HPX fell within the pre-defined equivalence margin, demonstrating equivalence between the two imaging modalities to a significance level of p