TY - JOUR
T1 - Sildenafil for treating patients with COVID-19 and perfusion mismatch
T2 - a pilot randomized trial
AU - Santamarina, Mario G.
AU - Beddings, Ignacio
AU - Lomakin, Felipe Martinez
AU - Boisier Riscal, Dominique
AU - Gutiérrez Claveria, Mónica
AU - Vidal Marambio, Jaime
AU - Retamal Báez, Nicole
AU - Pavez Novoa, Cristian
AU - Reyes Allende, César
AU - Ferreira Perey, Paulina
AU - Gutiérrez Torres, Miguel
AU - Villalobos Mazza, Camila
AU - Vergara Sagredo, Constanza
AU - Ahumada Bermejo, Sebastian
AU - Labarca Mellado, Eduardo
AU - Barthel Munchmeyer, Elizabeth
AU - Marchant Ramos, Solange
AU - Volpacchio, Mariano
AU - Vega, Jorge
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: SARS-CoV-2 seems to affect 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 efficacy of oral sildenafil 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-confirmed 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 sildenafil (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 differences 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 sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41–68] years. No significant differences 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 sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly 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 significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. Trial Registration: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446.
AB - Background: SARS-CoV-2 seems to affect 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 efficacy of oral sildenafil 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-confirmed 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 sildenafil (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 differences 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 sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41–68] years. No significant differences 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 sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly 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 significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. Trial Registration: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446.
KW - Blood gas analysis
KW - COVID-19
KW - Intensive care unit
KW - Length of stay
KW - Mechanical ventilation
KW - Sildenafil
KW - Subtraction CT angiography
KW - Ventilation–perfusion ratio
UR - http://www.scopus.com/inward/record.url?scp=85122187553&partnerID=8YFLogxK
U2 - 10.1186/s13054-021-03885-y
DO - 10.1186/s13054-021-03885-y
M3 - Article
C2 - 34980198
AN - SCOPUS:85122187553
SN - 1364-8535
VL - 26
JO - Critical Care
JF - Critical Care
IS - 1
M1 - 1
ER -