Sildenafil in COVID-19

Covid19 Clinical Trial

Official title:

Sildenafil for Treating Patients With COVID-19 and Perfusion Mismatch: A Pilot Randomised Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04489446
• Other study ID #: UNAB-003
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 19, 2020
• Est. completion date: June 30, 2021

Study information

• Verified date: September 2021
• Source: Universidad Nacional Andres Bello
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-COV2 Infection

Intervention

Drug:
• Sildenafil
Patients allocated to this arm will receive Sildenafil 25mg every 8 hours orally for up to seven consecutive days.
• 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.

Locations

Country	Name	City	State
Chile	Hospital Naval Almirante Nef	Viña Del Mar	Valparaiso

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Nacional Andres Bello	Hospital Naval Almirante Nef, Viña del Mar, Chile

Country where clinical trial is conducted

Chile, 

References & Publications (5)

Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ, Raizada MK, Grant MB, Oudit GY. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ Res. 2020 May 8;126(10):1456-1474. doi: 10.1161/CIRCRESAHA.120.317015. Epub 2020 Apr 8. Review. — View Citation

Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020 Jun 25;58(7):1131-1134. doi: 10.1515/cclm-2020-0198. — View Citation

Santamarina MG, Boisier D, Contreras R, Baque M, Volpacchio M, Beddings I. COVID-19: a hypothesis regarding the ventilation-perfusion mismatch. Crit Care. 2020 Jul 6;24(1):395. doi: 10.1186/s13054-020-03125-9. — View Citation

Wu Z, Hu R, Zhang C, Ren W, Yu A, Zhou X. Elevation of plasma angiotensin II level is a potential pathogenesis for the critically ill COVID-19 patients. Crit Care. 2020 Jun 5;24(1):290. doi: 10.1186/s13054-020-03015-0. — View Citation

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	Adverse events attributable to sildenafil use.	Up to two weeks after randomisation
Primary	Arterial Oxygenation	Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.	One hour after sildenafil administration
Primary	Arterial Oxygenation	Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.	Daily until the end of follow-up (up to 15 days after randomisation)
Primary	Alveolo-arterial gradient	Mean difference in the alveolo-arterial gradient between study groups.	One hour after sildenafil administration
Primary	Alveolo-arterial gradient	Mean difference in the alveolo-arterial gradient between study groups.	Daily until the end of follow-up (up to 15 days after randomisation)
Secondary	Intensive care unit admission	Proportion of patients requiring admission to an intensive care unit in each study group	Up to two weeks after randomisation
Secondary	Noninvasive Mechanical Ventilation or Requirement of High-Flow Nasal Cannula	Proportion of patients requiring noninvasive mechanical ventilation o high-flow nasal cannula unit in each study group	Up to two weeks after randomisation
Secondary	Invasive mechanical ventilation	Proportion of patients requiring invasive mechanical ventilation in each study group	Up to two weeks after randomisation
Secondary	Survival	Proportion of patients that survived COVID19 in each study group	Up to two weeks after randomisation

External Links

•   COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU)