Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial

Abstract

Background: SARS-CoV-2 seems to afect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation–perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efcacy of oral sildenafl in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. Methods: Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confrmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafl (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were diferences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. Results: Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafl group); 33 [82.5%] were male; and median age was 57 [IQR 41–68] years. No signifcant diferences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p=0.67 and p=0.69). IMV was required in 4 patients who received placebo and none in the sildenafl arm (logrank p=0.04). Patients in the sildenafl arm showed a signifcantly shorter median length of hospital stay than the placebo group (9 IQR 7–12 days vs. 12 IQR 9–21 days, p=0.04). Conclusions: No statistically signifcant diferences were found in the oxygenation parameters. Sildenafl treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specifc perfusion patterns in sCTA. A large-scale study is needed to confrm these results.