A Phase 4 interventional study of Macitentan in Cardiac Allograft Vasculopathy, sponsored by University of California, Los Angeles. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-12.
Sponsored by University of California, Los Angeles · Phase 4, Interventional, and Other
Many patients with end-stage heart failure, a condition in which the heart fails to pump enough blood to support the body's other organs, are fortunate enough to receive a heart transplant. However, despite taking medicines aimed at blunting the immune system's response to the donor heart, some of them will develop transplant-related disease in the coronary arteries supplying their hearts. Fifty years after the first human-to-human heart transplant, this disorder-cardiac allograft vasculopathy (CAV)-remains a leading cause of long-term death and has been coined the 'Achilles' Heel' of heart transplantation. Indeed, a better understanding of how CAV occurs and improved therapies to prevent and/or slow its development are desperately needed to meaningfully impact patient outcomes.
Endothelin-1 (ET-1) is a key molecular regulator of arterial health, and our prior data suggests that it is associated with accelerated CAV. In this particular study of recent heart transplant recipients, we are asking: Does ET-1 contribute to the coronary artery's capacity to dilate/constrict? To answer this question, during the cardiac catheterization at 1 year post-transplant (standard of care), we will measure blood levels of ET-1 and perform an invasive evaluation of coronary vasomotor function inn a consecutive subset of patients who will have received a 1-week course of the oral endothelin receptor antagonist (macitentan) prior this catheterization, which will allow us to test how much ET-1 contributes to coronary responsiveness.
The findings from this study may provide the necessary foundation to study whether endothelin receptor antagonists are able to effectively reduce the rate of accelerated CAV.
1,027 studies on the registry are indexed under Vascular Diseases; 167 are open to participants now.
This study's enrollment of 19 is below the median of 78 across 639 interventional studies indexed under Vascular Diseases.
Browse Vascular Diseases studies →University of California, Los Angeles is the lead sponsor of 1,142 studies on the registry; 192 are open to participants now.
Of its 91 completed or terminated interventional studies of FDA-regulated products, 66 (73%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
A consecutive subset of eligible patients based on inclusion/exclusion criteria will receive a 1-week course of Macitentan (10 mg po daily) prior to their routine 1-year coronary angiogram (7th and final dose of Macitentan will occur on the day of the angiogram).
Drug: Macitentan
Macitentan is a nonselective endothelin-receptor antagonist (ERA) that is approved for use in pulmonary arterial hypertension (PAH); the use of Macitentan in post-heart transplant patients is considered investigational.
Also known as: Opsumit
Macitentan: Nitroglycerin (NTG) Luminal Dilation Ratio as Proportion of Vasomotor Tone Attributable to Endothelin-1 (ET-1)
Macitentan: NTG luminal volume dilation ratio on Intravascular Ultrasound (IVUS). Vasodilation achieved by Macitentan was compared with that after intracoronary nitroglycerin, a maximal dilator of epicardial arteries, to determine the relative contribution of ET-1 to the overall resting vasomotor tone. The contribution of ET-1 to resting vasomotor tone is expressed as the ratio of dilation to Macitentan over the dilation to nitroglycerin.
Time frame: End of study week 1 (time of 1 year post-transplant coronary angiogram)
| Milestone | Intervention Arm |
|---|---|
| Started | 19 |
| Completed | 17 |
| Not completed | 2 |
| Withdrew: Withdrawal by subject | 2 |
Macitentan: NTG luminal volume dilation ratio on Intravascular Ultrasound (IVUS). Vasodilation achieved by Macitentan was compared with that after intracoronary nitroglycerin, a maximal dilator of epicardial arteries, to determine the relative contribution of ET-1 to the overall resting vasomotor tone. The contribution of ET-1 to resting vasomotor tone is expressed as the ratio of dilation to Macitentan over the dilation to nitroglycerin.
| ratio | Participants With Progressive Cardiac Allograft Vasculopathy (CAV) at 1-year Post-transplant | Participants Without Progressive Cardiac Allograft Vasculopathy (CAV) at 1-year Post-transplant |
|---|---|---|
| Macitentan: Nitroglycerin (NTG) Luminal Dilation Ratio as Proportion of Vasomotor Tone Attributable to Endothelin-1 (ET-1) | 0.33 (0.31 to 0.37) | 0.30 (0.29 to 0.32) |
Collected over One week prior to one-year post-transplant angiogram (Day -7 to Study Day). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Intervention Arm | 0/19 (0%) | 0/19 (0%) | 0/19 (0%) |
| Age, Continuous(years) | Intervention Arm |
|---|---|
| Mean | 54.2 (42.8 to 65.7) |
| Sex: Female, Male(Participants) | Intervention Arm |
|---|---|
| Female | 4 |
| Male | 15 |
| Race/Ethnicity, Customized(Participants) | Intervention Arm |
|---|---|
| Hispanic | 6 |
| Non-Hispanic White | 10 |
| Non-Hispanic Black | 1 |
| Non-Hispanic Asian | 1 |
| Other | 1 |
| Region of Enrollment(participants) | Intervention Arm |
|---|---|
| United States | 19 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of California, Los Angeles