Sildenafil in COVID-19

NCT04489446 | Completed Phase 1

• 1 other identifier: UNAB-003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Covid19; SARS-COV2 Infection

Keywords

COVID19; SARS-COV2 Infection; Sildenafil; Phosphodiesterase 5 inhibitors

Outcome Measures

Primary Outcomes (4)

• Arterial Oxygenation

  Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.

  One hour after sildenafil administration

• 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)

• Alveolo-arterial gradient

  Mean difference in the alveolo-arterial gradient between study groups.

  One hour after sildenafil administration

• 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 Outcomes (4)

• Intensive care unit admission

  Up to two weeks after randomisation

• Noninvasive Mechanical Ventilation or Requirement of High-Flow Nasal Cannula

  Up to two weeks after randomisation

• Invasive mechanical ventilation

  Up to two weeks after randomisation

• Survival

  Up to two weeks after randomisation

Other Outcomes (1)

• Adverse events

  Up to two weeks after randomisation

Study Arms (2)

Sildenafil

EXPERIMENTAL

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

Drug: Sildenafil

Control

PLACEBO COMPARATOR

Patients allocated to this arm will receive a placebo that will be similar in form to sildenafil pills in the interventional arm. These doses will be scheduled every 8 hours and wil be administered orally por up to seven consecutive days.

Drug: Placebo

Interventions

Sildenafil DRUG

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

Sildenafil

Placebo DRUG

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.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidad Nacional Andres Bello: lead
• Hospital Naval Almirante Nef, Viña del Mar, Chile: collaborator

Study Sites (1)

Hospital Naval Almirante Nef

Viña del Mar, Región de Valparaíso, Chile

Location

Related Publications (6)

• 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.

  PMID: 32171076 BACKGROUND

• 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. No abstract available.

  PMID: 32119647 BACKGROUND

• 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. No abstract available.

  PMID: 32631389 BACKGROUND

• 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.

  PMID: 32264791 BACKGROUND

• 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. No abstract available.

  PMID: 32503680 BACKGROUND

• Santamarina MG, Beddings I, Lomakin FM, Boisier Riscal D, Gutierrez Claveria M, Vidal Marambio J, Retamal Baez N, Pavez Novoa C, Reyes Allende C, Ferreira Perey P, Gutierrez Torres M, Villalobos Mazza C, Vergara Sagredo C, Ahumada Bermejo S, Labarca Mellado E, Barthel Munchmeyer E, Marchant Ramos S, Volpacchio M, Vega J. Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial. Crit Care. 2022 Jan 3;26(1):1. doi: 10.1186/s13054-021-03885-y.

  PMID: 34980198 DERIVED

Related Links

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

MeSH Terms

Conditions

COVID-19

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mario Santamarina, MD

  Hospital Naval Almirante Nef

  STUDY DIRECTOR

• Felipe Martinez, MD, MSc

  Universidad Andres Bello

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Model Details: Eligible participants will be randomised to either sildenafil or placebo for up to seven days.

Study Record Dates

• First Submitted: July 25, 2020
• First Posted: July 28, 2020
• Study Start: August 19, 2020
• Primary Completion: April 30, 2021
• Study Completion: June 30, 2021
• Last Updated: September 29, 2021

Record last verified: 2021-09

Locations

CL (1)