The POST-ACS Study
Potential Impact of Oral Semaglutide on Coronary Artery Disease Progression Following Acute Coronary Syndrome: The POST-ACS Study
1 other identifier
interventional
140
1 country
1
Brief Summary
Individuals with T2DM have a two-fold excess risk of cardiovascular (CV) events compared with their non-diabetic counterparts. Although it is the primary cause of death in T2DM, there is no significant evidence that intensive glucose lowering reduces CV events. Multiple Cardiovascular Outcome Trials have suggested CV safety and benefit with the new class hypoglycemic agents - glucagon-like peptide 1 receptor agonists (GLP-RAs) in patients with DM and a high CV risk profile with a mechanism not directly dependent on their glucose-lowering effect. Varies theories regarding the mechanism of action of GLP-RAs on reducing CV events have been proposed, including reducing inflammation, protection of ischemia/reperfusion injury, and improvement in endothelial dysfunction but the effects of these new agents on in-vivo atherosclerotic plaque burden is currently unproven. The investigators hypothesize that compared with placebo, 1-year treatment with the oral GLP-RA "Semaglutide" will result in a regression of necrotic core within potentially vulnerable coronary plaques (identified using the novel method "Plaque Maps" analysis on CT Coronary Angiography) in patients with raised HbA1c (\>5.7%) after acute coronary syndromes (ACS). Methods: One hundred forty patients admitted with ACS and have raised HbA1c \>5.7% will be enrolled in the trial and randomized in a 1:1 blinded fashion to receive conventional therapy and initiation of Semaglutide or conventional therapy plus placebo. All patients will have a CT Coronary Angiography with Plaque Map analysis of atherosclerotic burden, plaque composition and presence of potentially vulnerable plaque morphology at baseline prior to therapy initiation and following 12 months of treatment. In addition, to help elucidate the potential mechanisms of any anti-atherosclerotic effects, patients will have a non-invasive assessment of vascular function assessed by aortic pulse wave velocity and comprehensive biomarker analysis of inflammation, atherogenesis and oxidative stress.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4 diabetes-mellitus
Started Aug 2022
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 11, 2022
CompletedFirst Posted
Study publicly available on registry
April 11, 2022
CompletedStudy Start
First participant enrolled
August 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 28, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2024
CompletedOctober 27, 2022
October 1, 2022
1.7 years
February 11, 2022
October 25, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Compare the regression of vulnerable coronary plaque (necrotic core) assessed using histologically validated "Plaque Maps" derived from CT Coronary angiography in patients with raised HbA1c admitted with ACS and treated with oral Semaglutide or placebo.
Reduction in mean coronary plaque necrotic core (%) identified by CT Coronary Angiography Plaque Maps after 12-month therapy (Semaglutide or placebo).
12 months
Secondary Outcomes (4)
-Evaluate the effect of oral Semaglutide on atherosclerotic plaque burden.
12 months
Evaluate the effect of oral Semaglutide on levels of biomarkers of inflammation.
12 months
-Evaluate any potential effect of oral Semaglutide on arterial stiffness
12 months
Evaluate the effect of oral Semaglutide on levels of biomarkers of oxidative stress.
12 months
Study Arms (2)
Active drug
ACTIVE COMPARATOROral Semaglutide + conventional therapy (includes dual antiplatelets, Statin, Angiotensin-converting enzyme inhibitors (ACE inhibitors) and beta-blockers)
Placebo
PLACEBO COMPARATORplacebo (same dose and administration route) + conventional therapy (includes dual antiplatelets, Statin, Angiotensin-converting enzyme inhibitors (ACE inhibitors) and beta-blockers)
Interventions
Participants in both arms will undergo CT coronary angiogram with Plaque Map analysis at baseline prior to therapy initiation and following 12 months of treatment.
Participants in both arms will undergo aortic carotid-femoral pulse wave velocity (cfPWV)through the Vicorder (Skidmore medical, UK), which uses oscillometric cuff-based measurements to establish the index of arterial stiffness. The procedure will be done at baseline and 12 months after therapy initiation.
All the participants will have (non-fasting) blood samples performed to assess serum glucose, lipid profile and serum biomarkers for plaque initiation (Lipid profile, LpPLA2), endothelial activation (MCP-1), plaque inflammation (hsCRP, IL6, IL18, TNF, advanced glycation end-products), vulnerable transformation (vEGF, PAI-1, BMP-6) and measures of oxidative stress (Ox-LDL, TAOS, TBARs) at baseline, and at 12 months after therapy initiation
Eligibility Criteria
You may qualify if:
- HbA1c \> 5.7% (39 mmol/mol)
- Patients presented with a clinical diagnosis of ACS comprising detection of a rise and/or fall of cardiac troponin (cTn) with at least one value above the 99th percentile and with at least one of the following:
- Symptoms of acute myocardial ischemia;
- New ischemic electrocardiographic (ECG) changes (ST-T wave changes or new LBBB);
- Development of pathological Q waves;
- Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic aetiology;
- Identification of a coronary thrombus by angiography including intracoronary imaging or by autopsy
You may not qualify if:
- Type 1 DM
- Left ventricular ejection fraction \<40%
- Heart failure classified as being in New York Heart Association (NYHA) Class III-IV.
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation.
- History of renal insufficiency with estimated glomerular filtration rate \<30mL/min/1.73m2
- A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- History of treatment with GLP-1 within 90 days before screening
- Current use of SGLT-2 inhibitors within 30 days of screening
- Known or suspected hypersensitivity to Semaglutide or related products.
- Female who is pregnant, breastfeeding or intends to become pregnant, or is of child-bearing potential and not using a highly effective contraceptive method.
- Current enrolment in any other clinical trial within 30 days from screening
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Swansea Bay University Health Board
Swansea, SA2 8QA, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2022
First Posted
April 11, 2022
Study Start
August 31, 2022
Primary Completion
April 28, 2024
Study Completion
August 1, 2024
Last Updated
October 27, 2022
Record last verified: 2022-10
Data Sharing
- IPD Sharing
- Will not share