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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
Ottawa Heart Institute Research Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients who have been selected to undergo alcohol septal ablation for hypertrophic obstructive cardiomyopathy based on clinical need
  2. Age >18 years, <80 years

Exclusion Criteria:

  1. Patients with known allergy to aspirin
  2. Inability or refusal to consent to participate in the study
  3. 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

First Posted
January 6, 2016
Last Updated
January 12, 2023
Sponsor
Ottawa Heart Institute Research Corporation
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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

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Mobilization of Endothelial Progenitor Cells and Aspirin

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