Clinical trial NCT04283240: Sildenafil in Acute Pulmonary Embolism
Official title: Pulmonary Vasodilation by Sildenafil in Acute Pulmonary Embolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Pulmonary Embolism
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2020-02-25
Enrollment: 20
Sex: ALL
Minimum age (years): 80
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Cardiac Index
timeFrame: 74 (plus/minus 17) minutes after drug administration
Secondary outcomes:
Other outcomes:
measure: Right ventricular stroke volume
timeFrame: 74 (plus/minus 17) minutes after drug administration
measure: Cardiac output
timeFrame: 74 (plus/minus 17) minutes after drug administration
measure: Right ventricular end diastolic volume
timeFrame: 74 (plus/minus 17) minutes after drug administration
measure: Right ventricular end systolic volume
timeFrame: 74 (plus/minus 17) minutes after drug administration
measure: Right ventricular ejection fraction
timeFrame: 74 (plus/minus 17) minutes after drug administration
measure: Mean longitudinal strain
timeFrame: 74 (plus/minus 17) minutes after drug administration
measure: Mean pulmonary capillary wedge pressure
timeFrame: 32 (plus/minus 5 min) minutes after drug administration
measure: diastolic pulmonary artery pressure
timeFrame: 32 (plus/minus 5 min) minutes after drug administration
measure: systolic pulmonary artery pressure
timeFrame: 32 (plus/minus 5 min) minutes after drug administration
measure: mean pulmonary artery pressure
timeFrame: 32 (plus/minus 5 min) minutes after drug administration
measure: Pulmonary vascular resistance
timeFrame: 32 (plus/minus 5 min) minutes after drug administration
measure: Venous oxygen saturation
timeFrame: 32 (plus/minus 5 min) minutes after drug administration
measure: Right ventricular/left ventricular diameter
timeFrame: 84 (plus/minus 40) minutes after drug administration
measure: Right ventricular fractional area change
timeFrame: 84 (plus/minus 40) minutes after drug administration
measure: Tricuspid annular plane systolic excursion
timeFrame: 84 (plus/minus 40) minutes after drug administration
measure: Pulmonary artery acceleration time
timeFrame: 84 (plus/minus 40) minutes after drug administration
measure: Tricuspid regurgitant gradient
timeFrame: 84 (plus/minus 40) minutes after drug administration
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Asger Andersen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.