Sildenafil in COVID-19

September 27, 2021 updated by: Felipe Martinez Lomakin, Universidad Nacional Andres Bello

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Chile
    • Valparaiso
      • Viña Del Mar, Valparaiso, Chile
        • Hospital Naval Almirante Nef

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sildenafil
Patients allocated to this arm will receive Sildenafil 25mg every 8 hours orally for up to seven consecutive days.
Drug: Sildenafil
Patients allocated to this arm will receive Sildenafil 25mg every 8 hours orally for up to seven consecutive days.
Placebo Comparator: Control
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Arterial Oxygenation
Time Frame: One hour after sildenafil administration
Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.
One hour after sildenafil administration
Arterial Oxygenation
Time Frame: Daily until the end of follow-up (up to 15 days after randomisation)
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
Time Frame: One hour after sildenafil administration
Mean difference in the alveolo-arterial gradient between study groups.
One hour after sildenafil administration
Alveolo-arterial gradient
Time Frame: Daily until the end of follow-up (up to 15 days after randomisation)
Mean difference in the alveolo-arterial gradient between study groups.
Daily until the end of follow-up (up to 15 days after randomisation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intensive care unit admission
Time Frame: Up to two weeks after randomisation
Proportion of patients requiring admission to an intensive care unit in each study group
Up to two weeks after randomisation
Noninvasive Mechanical Ventilation or Requirement of High-Flow Nasal Cannula
Time Frame: Up to two weeks after randomisation
Proportion of patients requiring noninvasive mechanical ventilation o high-flow nasal cannula unit in each study group
Up to two weeks after randomisation
Invasive mechanical ventilation
Time Frame: Up to two weeks after randomisation
Proportion of patients requiring invasive mechanical ventilation in each study group
Up to two weeks after randomisation
Survival
Time Frame: Up to two weeks after randomisation
Proportion of patients that survived COVID19 in each study group
Up to two weeks after randomisation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: Up to two weeks after randomisation
Adverse events attributable to sildenafil use.
Up to two weeks after randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Nacional Andres Bello

Collaborators

Hospital Naval Almirante Nef, Viña del Mar, Chile

Investigators

  • Study Director: Mario Santamarina, MD, Hospital Naval Almirante Nef
  • Principal Investigator: Felipe Martinez, MD, MSc, Universidad Andrés Bello

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 19, 2020

Primary Completion (Actual)

April 30, 2021

Study Completion (Actual)

June 30, 2021

Study Registration Dates

First Submitted

July 25, 2020

First Submitted That Met QC Criteria

July 25, 2020

First Posted (Actual)

July 28, 2020

Study Record Updates

Last Update Posted (Actual)

September 29, 2021

Last Update Submitted That Met QC Criteria

September 27, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UNAB-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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