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Sildenafil in COVID-19

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ClinicalTrials.gov Identifier: NCT04489446
Recruitment Status : Recruiting
First Posted : July 28, 2020
Last Update Posted : November 3, 2020
Sponsor:
Collaborator:
Hospital Naval Almirante Nef, Viña del Mar, Chile
Information provided by (Responsible Party):
Felipe Martinez Lomakin, Universidad Nacional Andres Bello

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

Condition or disease Intervention/treatment Phase
Covid19 SARS-COV2 Infection Drug: Sildenafil Drug: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Eligible participants will be randomised to either sildenafil or placebo for up to seven days.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sildenafil for Treating Patients With COVID-19 and Perfusion Mismatch: A Pilot Randomised Trial
Actual Study Start Date : August 19, 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Arterial Oxygenation [ Time Frame: One hour after sildenafil administration ]
    Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.

  2. 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.

  3. Alveolo-arterial gradient [ Time Frame: One hour after sildenafil administration ]
    Mean difference in the alveolo-arterial gradient between study groups.

  4. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Invasive mechanical ventilation [ Time Frame: Up to two weeks after randomisation ]
    Proportion of patients requiring invasive mechanical ventilation in each study group

  4. Survival [ Time Frame: Up to two weeks after randomisation ]
    Proportion of patients that survived COVID19 in each study group


Other Outcome Measures:
  1. Adverse events [ Time Frame: Up to two weeks after randomisation ]
    Adverse events attributable to sildenafil use.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04489446


Contacts
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Contact: Mario Santamarina, MD +56 32 2573399 mgsantama@yahoo.com
Contact: Felipe M Martinez, MD, MSc +56 32 2573399 felipe.martinez.l@unab.cl

Locations
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Chile
Hospital Naval Almirante Nef Recruiting
Viña Del Mar, Valparaiso, Chile
Contact: Mario Santamarina, MD    +5632 2573399    mgsantama@yahoo.com   
Principal Investigator: Ignacio Beddings, MD         
Principal Investigator: Dominique Boisier, MD         
Principal Investigator: Jaime Vidal, MD         
Principal Investigator: Cesar Reyes, MD         
Principal Investigator: Monica Gutierrez, MD         
Principal Investigator: Eduardo Labarca, MD         
Principal Investigator: Jorge Vega, MD         
Principal Investigator: Miguel Gutierrez, MD         
Principal Investigator: Roberto Contreras, MD         
Principal Investigator: Sebastian Ahumada, MD         
Sub-Investigator: Nicole Retamal         
Sponsors and Collaborators
Universidad Nacional Andres Bello
Hospital Naval Almirante Nef, Viña del Mar, Chile
Investigators
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Study Director: Mario Santamarina, MD Hospital Naval Almirante Nef
Principal Investigator: Felipe Martinez, MD, MSc Universidad Andres Bello
Additional Information:
Publications:
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Responsible Party: Felipe Martinez Lomakin, Investigator, Universidad Nacional Andres Bello
ClinicalTrials.gov Identifier: NCT04489446    
Other Study ID Numbers: UNAB-003
First Posted: July 28, 2020    Key Record Dates
Last Update Posted: November 3, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Felipe Martinez Lomakin, Universidad Nacional Andres Bello:
COVID19
SARS-COV2 Infection
Sildenafil
Phosphodiesterase 5 inhibitors
Additional relevant MeSH terms:
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Infection
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents