This randomised trial aims to assess the role of sildenafil in improving oxygenation amongst hospitalised patients with COVID19.

Perfusion anomalies, namely hypoperfusion of healthy lung and vasoplegia with hyperperfusion of diseased lung areas, have been recently described amongst patients with COVID19. In this triple-blind pilot randomised trial, adult patients with high clinical suspicion of SARS-CoV2 infection and perfusion defects in a substraction computed tomography angiography will be randomised in a 1:1 ratio to receive sildenafil or placebo. Informed consent will be obtained from every included participant. Patients requiring mechanical ventilation at baseline will be excluded, as will those who present a contraindication to sildenafil, previous users of sildenafil, those requiring therapy with nitrates, patients in which an order to limit therapeutic efforts has been issued, pregnant or breastfeeding women and those who decline to participate in this study. The primary outcome for this trial wil be oxygenation changes in blood gas analyses. Secondary outcomes will include clinical deterioration requiring admission to an intensive care unit, requirement of high-flow nasal cannula or invasive mechanical ventilation and overall survival. Patients will be followed-up until hospital discharge or up to fifteen days after randomisation. Statistical analyses will be undertaken by a statistician unaware of treatment allocation under the intention-to-treat principle.

Inclusion Criteria:

• Adult participant with high clinical suspicion of a SARS-CoV2 infection.
• Hypoperfusion of healthy lung areas in a substraction computed tomography angiography within 24 hours of admission to the hospital.

Exclusion Criteria:

• Requirement of therapy with nitrates of nitrites
• Arterial hypotension at presentation
• Recent diagnosis of coronary artery disease (<6 months)
• Acute heart failure at presentation
• Recent stroke (< 6 months)
• Chronic respiratory failure with CO2 retention
• Known hypersensitivity to sildenafil
• Advanced liver disease (Child-Pugh class B or higher)
• Users of cytochrome P450 3A4 inhibitors (Erythromycin, Ketoconazole, Itraconazole, Saquinavir)
• Pulmonary hypertension
• Chronic users of phosphodiesterase 5 inhibitors
• Requirement of invasive mechanical ventilation at baseline
• Decision to limit therapeutic efforts at baseline
• Pregnancy or lactation
• History of retinitis pigmentosa
• Known obstruction to left-ventricular outflow tract
• Unwillingness to participate in the trial