Macitentan to Prevent PRVO

NCT05946811 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: HP-00106867
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Embolism

Keywords

macitentan; pulmonary embolism; pulmonary hypertension; post-PE syndrome

Outcome Measures

Primary Outcomes (1)

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

  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.

  3 months

Secondary Outcomes (2)

• The difference in levels of biomarkers of endothelial dysfunction and vascular remodeling

  3 months

• The difference in scores of functional capacity and severity of pulmonary hypertension

  6 months

Study Arms (2)

Macitentan arm

EXPERIMENTAL

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

Drug: Macitentan 10mg

Placebo

PLACEBO COMPARATOR

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

Drug: Macitentan 10mg

Interventions

Macitentan 10mg DRUG

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

Macitentan arm; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Pulmonary Embolism; Hypertension, Pulmonary

Interventions

macitentan

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Hypertension

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: July 14, 2023
• Study Start: May 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)