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

• Published in: Critical care (London, England) England), 2022-01, Vol.26 (1), p.1-1, Article 1
• Main Authors: Santamarina, Mario G, Beddings, Ignacio, Lomakin, Felipe Martinez, Boisier Riscal, Dominique, Gutiérrez Claveria, Mónica, Vidal Marambio, Jaime, Retamal Báez, Nicole, Pavez Novoa, Cristian, Reyes Allende, César, Ferreira Perey, Paulina, Gutiérrez Torres, Miguel, Villalobos Mazza, Camila, Vergara Sagredo, Constanza, Ahumada Bermejo, Sebastian, Labarca Mellado, Eduardo, Barthel Munchmeyer, Elizabeth, Marchant Ramos, Solange, Volpacchio, Mariano, Vega, Jorge
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Blood gas analysis; Comorbidity; Confidence intervals; Coronaviruses; COVID-19; COVID-19 - drug therapy; COVID-19 - physiopathology; Critical care; Disease; Dosage and administration; Enzymes; Female; Humans; Hypertension; Laboratories; Male; Mechanical ventilation; Medical imaging; Middle Aged; Mortality; Patients; Pilot Projects; Pneumonia; Severe acute respiratory syndrome coronavirus 2; Sildenafil; Sildenafil Citrate - administration & dosage; Software; Subtraction CT angiography; Survival analysis; Testing; Treatment Outcome; Variance analysis; Vasodilator Agents - administration & dosage; Ventilation-Perfusion Ratio; Ventilators
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-021-03885-y

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. 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 (PaO /FiO 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. 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 PaO /FiO 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). 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. 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 .