Covid19, SARS-COV2 Infection
Conditions
Keywords
COVID19, SARS-COV2 Infection, Sildenafil, Phosphodiesterase 5 inhibitors
Brief summary
This randomised trial aims to assess the role of sildenafil in improving oxygenation amongst hospitalised patients with COVID19.
Detailed description
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.
Interventions
DRUGSildenafil
Patients allocated to this arm will receive Sildenafil 25mg every 8 hours orally for up to seven consecutive days.
DRUGPlacebo
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.
Sponsors
Hospital Naval Almirante Nef, Viña del Mar, Chile
Universidad Nacional Andres Bello
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Eligible participants will be randomised to either sildenafil or placebo for up to seven days.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alveolo-arterial gradient | One hour after sildenafil administration | Mean difference in the alveolo-arterial gradient between study groups. |
| Arterial Oxygenation | One hour after sildenafil administration | Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Noninvasive Mechanical Ventilation or Requirement of High-Flow Nasal Cannula | Up to two weeks after randomisation | Proportion of patients requiring noninvasive mechanical ventilation o high-flow nasal cannula unit in each study group |
| Survival | Up to two weeks after randomisation | Proportion of patients that survived COVID19 in each study group |
| Invasive mechanical ventilation | Up to two weeks after randomisation | Proportion of patients requiring invasive mechanical ventilation in each study group |
| Intensive care unit admission | Up to two weeks after randomisation | Proportion of patients requiring admission to an intensive care unit in each study group |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Up to two weeks after randomisation | Adverse events attributable to sildenafil use. |
Countries
Chile
Outcome results
None listed