MAC-PRO: Macitentan to Prevent PRVO

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05946811

Collaborator

(none)

128

Enrollment

Location

Arms

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism	Drug: Macitentan 10mg	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

128 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Role of MACitentan on the Prevention of Residual Pulmonary vasculaR Occlusion

Anticipated Study Start Date :

May 1, 2024

Anticipated Primary Completion Date :

Jan 1, 2028

Anticipated Study Completion Date :

Jun 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Macitentan arm Participants allocated to this arm will receive Macitentan 10 mg daily for 3 months	Drug: Macitentan 10mg Macitentan 10 mg oral once daily for 3 months. vs placebo
Placebo Comparator: Placebo Participants allocated to this arm will receive placebo daily for 3 months.	Drug: Macitentan 10mg Macitentan 10 mg oral once daily for 3 months. vs placebo

Arm

Intervention/Treatment

Experimental: Macitentan arm

Participants allocated to this arm will receive Macitentan 10 mg daily for 3 months

Drug: Macitentan 10mg

Macitentan 10 mg oral once daily for 3 months. vs placebo

Placebo Comparator: Placebo

Participants allocated to this arm will receive placebo daily for 3 months.

Drug: Macitentan 10mg

Macitentan 10 mg oral once daily for 3 months. vs placebo

Outcome Measures

Primary Outcome Measures

The percentage of pulmonary artery occlusion (Residual pulmonary vascular occlusion or RPVO) [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.

Secondary Outcome Measures

The difference in levels of biomarkers of endothelial dysfunction and vascular remodeling [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.
The difference in scores of functional capacity and severity of pulmonary hypertension [6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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