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.
Drug: Sildenafil
Patients allocated to this arm will receive Sildenafil 25mg every 8 hours orally for up to seven consecutive days.
Drug: Placebo
Patients allocated to this arm will receive a matching placebo similar to Sildenafil pills used in the intervention arm. Placebos will be delivered orally every 8 hours for up to seven consecutive days.
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
Hospital Naval Almirante Nef
Viña Del Mar, Valparaiso, Chile