Mobilization of Endothelial Progenitor Cells and Aspirin (TROPHIC 3)
Primary Purpose
Hypertrophic Obstructive Cardiomyopathy
Status
Terminated
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Aspirin
Sponsored by
About this trial
This is an interventional basic science trial for Hypertrophic Obstructive Cardiomyopathy focused on measuring endothelial progenitor cells, aspirin, acetylsalicylic acid, alcohol septal ablation
Eligibility Criteria
Inclusion Criteria:
- Patients who have been selected to undergo alcohol septal ablation for hypertrophic obstructive cardiomyopathy based on clinical need
- Age >18 years, <80 years
Exclusion Criteria:
- Patients with known allergy to aspirin
- Inability or refusal to consent to participate in the study
- Patients who are on non-steroidal anti-inflammatory drugs and cannot be stopped for the duration of the study
Sites / Locations
- University of Ottawa Heart Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Aspirin
No aspirin
Arm Description
Aspirin 325mg orally bolus followed by 162mg orally daily during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.
No aspirin allowed during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.
Outcomes
Primary Outcome Measures
Maximum circulating endothelial progenitor cells as a ratio to baseline at any timepoint
Change in number of EPCs measured at 0 (baseline), 1, 6, 24, 72 hours and on day 7 post procedure
Secondary Outcome Measures
Endothelial cell migration in vitro compared to baseline at any timepoint
Change in endothelial migration measured at 0,1, 6, 24, 72 hours and on day 7 post procedure
Full Information
NCT ID
NCT02674958
First Posted
January 6, 2016
Last Updated
January 12, 2023
Sponsor
Ottawa Heart Institute Research Corporation
1. Study Identification
Unique Protocol Identification Number
NCT02674958
Brief Title
Mobilization of Endothelial Progenitor Cells and Aspirin
Acronym
TROPHIC 3
Official Title
Mobilization of Endothelial Progenitor Cells Following Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: Randomized Controlled Trial of Aspirin
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Covid-19 pandemic
Study Start Date
May 2016 (Actual)
Primary Completion Date
April 1, 2022 (Actual)
Study Completion Date
April 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Heart Institute Research Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Aspirin at doses used during acute myocardial infarction may inhibit the mobilization of endothelial progenitor cells (EPCs).
Detailed Description
Aspirin has been shown to lower the number of EPCs in a time- and concentration-dependent manner. In vitro studies also show that aspirin may reduce the migratory and adhesive capacity of isolated EPCs, inhibit iNOS and tubule formation, which are pre-requisites for angiogenesis. This is relevant when patients are given a loading dose of 325mg at the time of diagnosis of acute myocardial infarction where higher numbers of EPCs have been associated with better outcomes. Furthermore, in the PLATO (Platelet Inhibition and Patient Outcomes) trial, high dose aspirin appeared to counteract the beneficial effect seen when ticagrelor or clopidogrel was used with low doses of aspirin in acute coronary syndromes (ACS).
As aspirin is currently standard of care in the management of ACS, it is difficult to conduct a study of the effect of aspirin versus placebo in that scenario. However, during alcohol septal ablation for hypertrophic obstructive cardiomyopathy, the indication for an antiplatelet agent is not well defined and varies between operators. When a small amount of myocardium is deliberately destroyed in this process, it serves as an ideal model to study the effect of aspirin on the biology of EPCs in vivo. This could provide an explanation to the different effects of high versus low dose aspirin when combined with a second antiplatelet agent in the management of ACS.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertrophic Obstructive Cardiomyopathy
Keywords
endothelial progenitor cells, aspirin, acetylsalicylic acid, alcohol septal ablation
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aspirin
Arm Type
Active Comparator
Arm Description
Aspirin 325mg orally bolus followed by 162mg orally daily during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.
Arm Title
No aspirin
Arm Type
No Intervention
Arm Description
No aspirin allowed during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
Acetylsalicylic acid
Intervention Description
Aspirin 325mg bolus followed by 162mg daily until day 7 post alcohol septal ablation
Primary Outcome Measure Information:
Title
Maximum circulating endothelial progenitor cells as a ratio to baseline at any timepoint
Description
Change in number of EPCs measured at 0 (baseline), 1, 6, 24, 72 hours and on day 7 post procedure
Time Frame
0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
Secondary Outcome Measure Information:
Title
Endothelial cell migration in vitro compared to baseline at any timepoint
Description
Change in endothelial migration measured at 0,1, 6, 24, 72 hours and on day 7 post procedure
Time Frame
0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
Other Pre-specified Outcome Measures:
Title
Peak SDF-1 level
Description
Change in level of SDF-1 at 0, 1, 6, 24, 72 hours and on day 7 post procedure
Time Frame
0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
Title
Peak angiopoietin-1 level
Description
Change in level of angiopoietin-1 at 0, 1, 6, 24, 72 hours and day 7 post procedure
Time Frame
0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Title
Peak angiopoietin-2 level
Description
Change in level of angiopoietin-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure
Time Frame
0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Title
Peak tie-2 level
Description
Change in level of tie-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure
Time Frame
0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Title
Peak vascular endothelial growth factor (VEGF) level
Description
Change in level of VEGF at 0, 1, 6, 24, 72 hours and on day 7 post procedure
Time Frame
0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who have been selected to undergo alcohol septal ablation for hypertrophic obstructive cardiomyopathy based on clinical need
Age >18 years, <80 years
Exclusion Criteria:
Patients with known allergy to aspirin
Inability or refusal to consent to participate in the study
Patients who are on non-steroidal anti-inflammatory drugs and cannot be stopped for the duration of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aun-Yeong Chong, MD, MRCP
Organizational Affiliation
OHIRC
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
16539843
Citation
Chen TG, Chen JZ, Xie XD. Effects of aspirin on number, activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood. Acta Pharmacol Sin. 2006 Apr;27(4):430-6. doi: 10.1111/j.1745-7254.2006.00298.x.
Results Reference
result
PubMed Identifier
20659762
Citation
Lou J, Povsic TJ, Allen JD, Adams SD, Myles S, Starr AZ, Ortel TL, Becker RC. The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties. Thromb Res. 2010 Sep;126(3):e175-9. doi: 10.1016/j.thromres.2009.11.017. Epub 2010 Jul 24.
Results Reference
result
PubMed Identifier
23713888
Citation
Etulain J, Fondevila C, Negrotto S, Schattner M. Platelet-mediated angiogenesis is independent of VEGF and fully inhibited by aspirin. Br J Pharmacol. 2013 Sep;170(2):255-65. doi: 10.1111/bph.12250.
Results Reference
result
Learn more about this trial
Mobilization of Endothelial Progenitor Cells and Aspirin
We'll reach out to this number within 24 hrs