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

Critical Care

Paulina Ferreira Perey¹  Miguel Gutiérrez Torres¹  Jorge Vega²  Solange Marchant Ramos³  Elizabeth Barthel Munchmeyer⁴  Camila Villalobos Mazza⁴  Jaime Vidal Marambio⁵  Nicole Retamal Báez⁵  Cristian Pavez Novoa⁵  Dominique Boisier Riscal⁵  Eduardo Labarca Mellado⁵  Constanza Vergara Sagredo⁵  Felipe Martinez Lomakin⁶  César Reyes Allende⁷  Mariano Volpacchio⁸  Ignacio Beddings⁹  Mario G. Santamarina^1,10  Mónica Gutiérrez Claveria^1,11  Sebastian Ahumada Bermejo^1,11 

[1] General Internal Medicine Department, Hospital Naval Almirante Nef, Viña del Mar, Chile;General Internal Medicine Department, Hospital Naval Almirante Nef, Viña del Mar, Chile;Departamento de Medicina, Escuela de Medicina, Universidad de Valparaíso, Viña del Mar, Chile;Hospital Pharmacy Department, Hospital Naval Almirante Nef, Viña del Mar, Chile;Infectious Disease Department, Hospital Naval Almirante Nef, Viña del Mar, Chile;Intensive Care Unit, Hospital Naval Almirante Nef, Viña del Mar, Chile;Intensive Care Unit, Hospital Naval Almirante Nef, Viña del Mar, Chile;Escuela de Medicina, Facultad de Medicina, Universidad Andres Bello, Viña del Mar, Chile;Intensive Care Unit, Hospital Naval Almirante Nef, Viña del Mar, Chile;Respiratory Department, Hospital Naval Almirante Nef, Viña del Mar, Chile;Radiology Department, Centro de Diagnóstico Dr. Enrique Rossi, Buenos Aires, Argentina;Radiology Department, Hospital Clínico San Borja Arriarán, Santiago, Chile;Radiology Department, Hospital Naval Almirante Nef, Subida Alesandri S/N., 254000, Viña del Mar, Provincia de Valparaíso, Chile;Radiology Department, Hospital Dr. Eduardo Pereira, Valparaiso, Chile;Respiratory Department, Hospital Naval Almirante Nef, Viña del Mar, Chile;

关键词: COVID-19;    Sildenafil;    Subtraction CT angiography;    Ventilation–perfusion ratio;    Blood gas analysis;    Mechanical ventilation;    Intensive care unit;    Length of stay;   

DOI  :  10.1186/s13054-021-03885-y

来源: Springer

【 摘 要 】

BackgroundSARS-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.MethodsTriple-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.ResultsTotally, 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).ConclusionsNo 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.

【 授权许可】

CC BY