Nintedanib in Post-COVID Interstitial Lung Disease: a double-blind, randomized, placebo-controlled Clinical Trial

Abstract Rationale The optimal treatment of interstitial lung disease resulting from COVID-19 is unknown. Objectives We sought to investigate the effect of nintedanib, an antifibrotic medication, on interstitial lung disease in participants who survived severe SARS-CoV-2 infection. Methods We conducted a double-blind, randomized, placebo-controlled trial at six sites across the United States. Participants were included if they had evidence of prior SARS-CoV-2 infection that required supplemental oxygen therapy and had interstitial lung disease (ILD) findings on chest imaging ≥ 30 days post-infection. Participants received either nintedanib or placebo (1:1 ratio) for 180 days. Primary outcome was change in forced vital capacity (FVC) at 180 days; other outcomes included changes in chest computed tomography imaging (qualitative and quantitative), six-minute walk distance, and patient-reported outcome measures. Measurements and Main Results In total, 103 of the planned 170 participants were randomized (51 to nintedanib; 52 to placebo); the study closed to enrollment before target sample size was met. FVC at 180 days improved in both nintedanib (+147.55 mL) and placebo groups (+167.72 mL) but were not significantly different (difference, -20.17 mL; 95% CI: -138.54 to 98.20). Similarly, six-minute walk distance, diffusing capacity, qualitative assessments of chest imaging, and patient-reported outcome measures improved in both groups. Quantitative chest imaging, as measured by data-driven textural analysis, showed no difference in fibrotic score changes for those receiving nintedanib or placebo (-4.49 vs -4.06; difference, -0.43; 95% CI: -3.34 to 2.47). Conclusions Administration of nintedanib in this limited trial did not result in improved outcomes for participants with post-COVID-19 ILD.