Clinical trial NCT05946811: Macitentan to Prevent PRVO
Official title: The Role of MACitentan on the Prevention of Residual Pulmonary vasculaR Occlusion
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Pulmonary Embolism
Keywords: macitentan
pulmonary embolism
pulmonary hypertension
post-PE syndrome
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2023-07-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: About half of patients who suffer of a pulmonary embolism (blood clots in the lungs), do not clear completely the clots overtime, increasing the risk of having a new blood clot in the lungs and elevated blood pressure in the pulmonary artery; therefore, developing fatigue, shortness of breath, and heart failure.

The objective of this clinical trial is to compare 3 months of daily Macitentan (a medicine to increase the diameter of the pulmonary artery) in addition to blood thinners vs. blood thinners alone in patients with acute blood clots in the pulmonary artery:

Question 1: Whether the use of Macitentan in addition to blood thinners enhances the process of cleaning the blood clot in the pulmonary artery compared to blood thinners alone.

Question 2: Whether the use of Macitentan in addition to blood thinners is associated to improve the fatigue and shortness of breath in patients after a pulmonary embolism compared to blood thinners alone.

Participants will be asked to take a capsule for 3 months in addition to blood thinners. The capsule could contain either Macitentan (medicine) or a placebo (not medicine). In 3 months, participants will have a new image of the pulmonary artery to document the cleaning of the clots. Also, blood and urine samples will be collected, as well as a questionnaire will be filled out. In 6 months, patients will have repeated images of the heart as well as repeated questionnaires.


Eligibility criteria: Inclusion Criteria:

* Age 18-75 years old.
* Acute high-risk or intermediate-risk PE diagnosed by CTPA within 28 days prior to enrollment

Exclusion Criteria:

* Contraindication for anticoagulation
* Allergy or contraindications to Macitentan or any other endothelin receptor antagonist.
* Surgical interventions to treat PE including catheter-directed thrombolysis, catheter-based thrombectomy, or surgical pulmonary embolectomy.
* Known inherited or acquired hypercoagulable states
* History of pulmonary embolism prior to index PE
* History of pulmonary hypertension including Group 1 (Primary pulmonary hypertension), Group 2 (secondary to left heart disease), Group 3 (secondary to lung disease), Group 4 (Chronic thromboembolic pulmonary hypertension)
* Severe chronic obstructive pulmonary disease
* Severe uncontrolled asthma
* Pregnancy or fertility treatment
* Breastfeeding
* Life expectancy is less than 6 months
* History of radiation therapy to the chest
* Current or previous use within 90 days of an endothelin-receptor antagonist, prostacyclin analogue, phosphodiesterase type 5 inhibitor, or nitric oxide donor.
* Severe allergic reaction to iodine contrast
* Subjects receiving CYP3A4 and CYP2C9 inhibitors or inducers such as rifampin, ritonavir, fluconazole, amiodarone
* Not able to read or understand the English language

Primary outcomes:
measure: The percentage of pulmonary artery occlusion (Residual pulmonary vascular occlusion or RPVO)
timeFrame: 3 months
Secondary outcomes:
measure: The difference in levels of biomarkers of endothelial dysfunction and vascular remodeling
timeFrame: 3 months
measure: The difference in scores of functional capacity and severity of pulmonary hypertension
timeFrame: 6 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
Study officials:
References: