Sildenafil in Acute Pulmonary Embolism (YGGDRASIL)

Pulmonary Vasodilation by Sildenafil in Acute Pulmonary Embolism

To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE).

Study Overview

• Status: Completed
• Conditions: Pulmonary Embolism
• Intervention / Treatment: Drug: Placebo; Drug: Sildenafil

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 80 years to 80 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sildenafil; 50 mg sildenafil oral. One dose	Drug: Sildenafil; 50 mg sildenafil, one dose
Placebo Comparator: Placebo; Placebo pill. One dose	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Index	Cardiac Index measured by cardiac magnetic resonance imaging	74 (plus/minus 17) minutes after drug administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricular stroke volume	Evaluated by cardiac magnetic resonance imaging	74 (plus/minus 17) minutes after drug administration
Cardiac output	Evaluated by cardiac magnetic resonance imaging	74 (plus/minus 17) minutes after drug administration
Right ventricular end diastolic volume	Evaluated by cardiac magnetic resonance imaging	74 (plus/minus 17) minutes after drug administration
Right ventricular end systolic volume	Evaluated by cardiac magnetic resonance imaging	74 (plus/minus 17) minutes after drug administration
Right ventricular ejection fraction	Evaluated by cardiac magnetic resonance imaging	74 (plus/minus 17) minutes after drug administration
Mean longitudinal strain	Evaluated by cardiac magnetic resonance imaging	74 (plus/minus 17) minutes after drug administration
Mean pulmonary capillary wedge pressure	Evaluated by Right heart catheterization	32 (plus/minus 5 min) minutes after drug administration
diastolic pulmonary artery pressure	Evaluated by Right heart catheterization	32 (plus/minus 5 min) minutes after drug administration
systolic pulmonary artery pressure	Evaluated by Right heart catheterization	32 (plus/minus 5 min) minutes after drug administration
mean pulmonary artery pressure	Evaluated by Right heart catheterization	32 (plus/minus 5 min) minutes after drug administration
Pulmonary vascular resistance	Evaluated by Right heart catheterization	32 (plus/minus 5 min) minutes after drug administration
Venous oxygen saturation	Evaluated by Right heart catheterization	32 (plus/minus 5 min) minutes after drug administration
Right ventricular/left ventricular diameter	Evaluated by echocardiography	84 (plus/minus 40) minutes after drug administration
Right ventricular fractional area change	Evaluated by echocardiography	84 (plus/minus 40) minutes after drug administration
Tricuspid annular plane systolic excursion	Evaluated by echocardiography	84 (plus/minus 40) minutes after drug administration
Pulmonary artery acceleration time	Evaluated by echocardiography	84 (plus/minus 40) minutes after drug administration
Tricuspid regurgitant gradient	Evaluated by echocardiography	84 (plus/minus 40) minutes after drug administration

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Asger Andersen, MD,PhD, Aarhus University Hospital

Publications and helpful links

General Publications

• Andersen A, Waziri F, Schultz JG, Holmboe S, Becker SW, Jensen T, Søndergaard HM, Dodt KK, May O, Mortensen UM, Kim WY, Mellemkjær 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): September 10, 2017
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (Actual): February 25, 2020

Study Record Updates

• Last Update Posted (Actual): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 21, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: 1-10-72-282-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: By request

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