Clinical trial NCT04224675: Captopril Versus Atenolol to Prevent Expansion Rate of Thoracic Aortic Aneurysms
Official title: Captopril Versus Atenolol to Prevent Expansion Rate of Thoracic Aortic Aneurysms
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Aneurysm
Lead sponsor: Onassis Cardiac Surgery Centre
Sponsor class: OTHER
First posted: 2020-01-13
Enrollment: 424
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Thoracic aortic aneurysms (TAA) are considered "silent killers" because they scarcely display any symptomatology, but are correlated with significant mortality and morbidity. Current guidelines regard aortic aneurysm disease as a coronary artery disease equivalent and suggest aspirin and statin use to reduce the progression of atherosclerosis, as well as beta-blocker (BB) therapy. No therapy, however, is effective at limiting aneurysm expansion and preventing rupture, even in large trials. TAA has emerged as an inflammation-mediated disorder. Angiotensin-converting enzyme inhibitors (ACEIs) can reduce the wall shear stress and inflammation, both of which play vital roles in the expansion of the aneurysm.

The study will be a randomized, double-blind trial. Patients will be randomized into one of two parallel arms, receiving captopril or atenolol. The doses of captopril and atenolol will be 25 mg daily for the first 15 days, rising to 100 mg according to clinical tolerance and BP estimates. The sample size will be set at 424 subjects (212 per group). The primary end-point will be the rate of change in the absolute diameter of the aortic root and ascending aorta on MRI of the aorta after 36 months of therapy with captopril vs. atenolol.

BBs have not been precisely found to decrease aneurysm growth rates. ACEIs could lead to the prevention of aneurysm degeneration through their antihypertensive and anti-inflammatory properties.

The results of this trial will clarify that ACEIs are superior to BB therapy in reducing the growth rate of TAAs, the rate of change in aortic insufficiency, the time to aortic rupture or dissection, the need for aortic surgery or intervention, and death.


Eligibility criteria: Inclusion Criteria:

All adult men or women, aged at least 70 years, with TAA 3.0-5.5 cm in diameter measurements according to magnetic resonance imaging (MRI) of the aorta and with a systolic BP \< 150 mmHg will be eligible for inclusion in the study.

Exclusion Criteria:

Patients already receiving an ACEI or BB daily, patients with known renal artery stenosis (\> 50%), patients incapable of providing informed consent, history of aortic dissection, angioedema or any intolerance to ACEIs or BBs, asthma, pregnancy, frailty, respiratory failure, and renal failure.

Primary outcomes:
measure: rate of change in the absolute diameter of the aortic root and ascending aorta on MRI of the aorta after 36 months of therapy with captopril vs. atenolol
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Spartalis M, Tzatzaki E, Iliopoulos DC, Spartalis E, Patelis N, Athanasiou A, Paschou SA, Voudris V, Siasos G. Captopril versus atenolol to prevent expansion rate of thoracic aortic aneurysms: rationale and design. Future Cardiol. 2021 Mar;17(2):189-195. doi: 10.2217/fca-2020-0062. Epub 2020 Aug 25.