Macitentan to Prevent PRVO (MAC-PRO)
The Role of MACitentan on the Prevention of Residual Pulmonary vasculaR Occlusion
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.
Study Overview
Study Type
Phase
- Phase 3
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21201
- University of Maryland Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Macitentan arm
Participants allocated to this arm will receive Macitentan 10 mg daily for 3 months
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Macitentan 10 mg oral once daily for 3 months.
vs placebo
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Placebo Comparator: Placebo
Participants allocated to this arm will receive placebo daily for 3 months.
|
Macitentan 10 mg oral once daily for 3 months.
vs placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
The percentage of pulmonary artery occlusion (Residual pulmonary vascular occlusion or RPVO)
Time Frame: 3 months
|
To quantify RPVO we will use the Qanadli index (QI).
The Qanadli index divides each pulmonary artery (right and left) into 10 segments.
The presence of a thrombus in a segmental artery is scored with 1 point, a thrombus in the most proximal arterial level is scored with a value equal to the number of segmental arteries arising from that artery.
The degree of obstruction score is obtained as follows: 0 when no thrombus, 1 is partially occlusive, and 2 is totally occlusive.
The maximum possible index is 40.
The percentage of obstruction is calculated using the following formula: % = QI Score /40 x 100.
Percent of obstruction will be calculated at baseline and 3-month CT scan.
The difference between 3 month-baseline percent of occlusion will be compared between Macitentan and placebo groups.
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3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
The difference in levels of biomarkers of endothelial dysfunction and vascular remodeling
Time Frame: 3 months
|
We will measure markers of endothelial dysfunction (CD31, CD41, CD62, CD144, CD54), change in diameter of brachial artery in millimeters from the flow mediated vasodilatation test (FMDba), FeNO levels in PPM and biomarkers of NO metabolism (ROS, ADMA, L-Arginine, Citrulline, NO and NOx) at baseline and at 3 months.
We will compare the difference between 3-month -baseline values between the Macitentan and the placebo groups.
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3 months
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The difference in scores of functional capacity and severity of pulmonary hypertension
Time Frame: 6 months
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We will obtain questionnaires of quality of life (SF-36 and PEmb), a six-minute walking test, and the pulmonary pressure by echocardiogram, at baseline and 3-month visit.
The difference between 3-month and baseline will be compared between the Macitentan and placebo groups.
|
6 months
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HP-00106867
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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