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Sildenafil in Acute Pulmonary Embolism (YGGDRASIL)

Primary Purpose

Pulmonary Embolism

Status
Completed
Phase
Early Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
Sildenafil
Placebo
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Pulmonary Embolism

Eligibility Criteria

80 Years - 80 Years (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with acute pulmonary embolism confirmed by contrast enhanced computed tomography (CT)
  • symptom duration of less than 14 days
  • older than 18-80 years
  • right ventricular/left ventricular ratio (RV/LV) >1 measured by trans-thoracic echocardiography (TTE, 1 cm above the atrio-ventricular valves in the four-chamber view at end-diastole).

Exclusion Criteria:

  • pregnant
  • cardiac arrest that required cardiopulmonary resuscitation
  • a life expectancy <120 days
  • systolic blood pressure <90 mmHg
  • metal implants, obesity or claustrophobia that excluded the patient from cardiac magnetic resonance (CMR)
  • altered mental status making the patient unable to provide informed consent
  • recent use of drugs with influence on the Nitric oxide-cyclic guanosine monophosphate pathway
  • known or suspected chronic thromboembolic pulmonary hypertension
  • inability to perform study protocol < 72 hours after conventional PE treatment was instituted
  • active bleeding after thrombolysis.

Sites / Locations

  • Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sildenafil

Placebo

Arm Description

50 mg sildenafil oral. One dose

Placebo pill. One dose

Outcomes

Primary Outcome Measures

Cardiac Index
Cardiac Index measured by cardiac magnetic resonance imaging

Secondary Outcome Measures

Full Information

First Posted
February 7, 2020
Last Updated
February 21, 2020
Sponsor
University of Aarhus
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1. Study Identification

Unique Protocol Identification Number
NCT04283240
Brief Title
Sildenafil in Acute Pulmonary Embolism
Acronym
YGGDRASIL
Official Title
Pulmonary Vasodilation by Sildenafil in Acute Pulmonary Embolism
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
March 1, 2015 (Actual)
Primary Completion Date
September 10, 2017 (Actual)
Study Completion Date
September 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE).
Detailed Description
Patients with PE randomized to a single oral dose of sildenafil 50mg (n=10) or placebo (n=10) as add-on to conventional therapy. Right ventricular function evaluated immediately before and shortly after (0.5-1.5h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Embolism

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Treatment was blinded by the institutional pharmacy embedding the placebo or treatment pill in a gelatinous cap
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sildenafil
Arm Type
Active Comparator
Arm Description
50 mg sildenafil oral. One dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo pill. One dose
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Intervention Description
50 mg sildenafil, one dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Cardiac Index
Description
Cardiac Index measured by cardiac magnetic resonance imaging
Time Frame
74 (plus/minus 17) minutes after drug administration
Other Pre-specified Outcome Measures:
Title
Right ventricular stroke volume
Description
Evaluated by cardiac magnetic resonance imaging
Time Frame
74 (plus/minus 17) minutes after drug administration
Title
Cardiac output
Description
Evaluated by cardiac magnetic resonance imaging
Time Frame
74 (plus/minus 17) minutes after drug administration
Title
Right ventricular end diastolic volume
Description
Evaluated by cardiac magnetic resonance imaging
Time Frame
74 (plus/minus 17) minutes after drug administration
Title
Right ventricular end systolic volume
Description
Evaluated by cardiac magnetic resonance imaging
Time Frame
74 (plus/minus 17) minutes after drug administration
Title
Right ventricular ejection fraction
Description
Evaluated by cardiac magnetic resonance imaging
Time Frame
74 (plus/minus 17) minutes after drug administration
Title
Mean longitudinal strain
Description
Evaluated by cardiac magnetic resonance imaging
Time Frame
74 (plus/minus 17) minutes after drug administration
Title
Mean pulmonary capillary wedge pressure
Description
Evaluated by Right heart catheterization
Time Frame
32 (plus/minus 5 min) minutes after drug administration
Title
diastolic pulmonary artery pressure
Description
Evaluated by Right heart catheterization
Time Frame
32 (plus/minus 5 min) minutes after drug administration
Title
systolic pulmonary artery pressure
Description
Evaluated by Right heart catheterization
Time Frame
32 (plus/minus 5 min) minutes after drug administration
Title
mean pulmonary artery pressure
Description
Evaluated by Right heart catheterization
Time Frame
32 (plus/minus 5 min) minutes after drug administration
Title
Pulmonary vascular resistance
Description
Evaluated by Right heart catheterization
Time Frame
32 (plus/minus 5 min) minutes after drug administration
Title
Venous oxygen saturation
Description
Evaluated by Right heart catheterization
Time Frame
32 (plus/minus 5 min) minutes after drug administration
Title
Right ventricular/left ventricular diameter
Description
Evaluated by echocardiography
Time Frame
84 (plus/minus 40) minutes after drug administration
Title
Right ventricular fractional area change
Description
Evaluated by echocardiography
Time Frame
84 (plus/minus 40) minutes after drug administration
Title
Tricuspid annular plane systolic excursion
Description
Evaluated by echocardiography
Time Frame
84 (plus/minus 40) minutes after drug administration
Title
Pulmonary artery acceleration time
Description
Evaluated by echocardiography
Time Frame
84 (plus/minus 40) minutes after drug administration
Title
Tricuspid regurgitant gradient
Description
Evaluated by echocardiography
Time Frame
84 (plus/minus 40) minutes after drug administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
80 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with acute pulmonary embolism confirmed by contrast enhanced computed tomography (CT) symptom duration of less than 14 days older than 18-80 years right ventricular/left ventricular ratio (RV/LV) >1 measured by trans-thoracic echocardiography (TTE, 1 cm above the atrio-ventricular valves in the four-chamber view at end-diastole). Exclusion Criteria: pregnant cardiac arrest that required cardiopulmonary resuscitation a life expectancy <120 days systolic blood pressure <90 mmHg metal implants, obesity or claustrophobia that excluded the patient from cardiac magnetic resonance (CMR) altered mental status making the patient unable to provide informed consent recent use of drugs with influence on the Nitric oxide-cyclic guanosine monophosphate pathway known or suspected chronic thromboembolic pulmonary hypertension inability to perform study protocol < 72 hours after conventional PE treatment was instituted active bleeding after thrombolysis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asger Andersen, MD,PhD
Organizational Affiliation
Aarhus University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
By request
Citations:
PubMed Identifier
33639897
Citation
Andersen A, Waziri F, Schultz JG, Holmboe S, Becker SW, Jensen T, Sondergaard HM, Dodt KK, May O, Mortensen UM, Kim WY, Mellemkjaer S, Nielsen-Kudsk JE. Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial. BMC Pulm Med. 2021 Feb 28;21(1):72. doi: 10.1186/s12890-021-01440-7.
Results Reference
derived

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Sildenafil in Acute Pulmonary Embolism

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