CLEAR SYNERGY Neutrophil Substudy

Study Overview
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Brief Summary
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CLEAR SYNERGY is an international multi center 2x2 randomized placebo controlled trial of colchicine and spironolactone in patients with STEMI. Subjects enrolled in the main CLEAR SYNERGY trial will be asked to participate in this sub study (n=670) to undergo: Evaluation of markers of neutrophil activity at randomization (baseline) and 3 months follow-up in the colchicine versus placebo groups, and; Examination of clinical and genetic factors that determine heterogeneity of treatment response and distinguish colchicine responders from non- responders. Participants undergo a blood draw at baseline and 3 months follow-up as part of the main trial, and participants who also participate in this sub study will have an additional 2 tablespoons of blood drawn. The sub study objectives are to: Assess the effect of colchicine on neutrophil activation in response to STEMI. Examine clinical and genetic factors that determine heterogeneity of treatment response anddistinguish colchicine responders from non- responders. Explore the derivation of a risk score that includes markers of neutrophil activity and is associated with adjudicated MACE over 3 years after STEMI, and assess the impact of colchicine on the relation between this risk score and MACE.

Official Title
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Studies on the Effects of Colchicine on Neutrophil Biology in Acute Myocardial Infarction: A Substudy of the CLEAR SYNERGY (OASIS 9) Trial

Conditions
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Neutrophils.Hypersegmented &#X7C; Bld-Ser-Plas, STEMI - ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Colchicine Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are randomized to the drug RCT portion of the CLEAR SYNERGY (OASIS 9) trial will be eligible for participation in this Neutrophil biomarker substudy. Exclusion Criteria: Use of anti-inflammatory agents (except aspirin) Active infection

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Colchicine<br> | Drug: Colchicine Pill<br>* Participants in the main CLEAR SYNERGY trial are randomized to colchicine/spironolactone versus placebo in a 2x2 factorial design. The substudy is interested in the evaluation of biospecimens obtained from patients in the colchicine vs placebo group.<br>|
| Placebo<br> | Drug: Colchicine Pill<br>* Participants in the main CLEAR SYNERGY trial are randomized to colchicine/spironolactone versus placebo in a 2x2 factorial design. The substudy is interested in the evaluation of biospecimens obtained from patients in the colchicine vs placebo group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| soluble L-selectin | Change in soluble L-selectin between baseline and 3 mo after STEMI in the placebo vs. colchicine groups. | between baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other soluble markers of neutrophil activity | Other markers of neutrophil activity will be evaluated at baseline and 3 months after STEMI (myeloperoxidase, matrix metalloproteinase-9, neutrophil gelatinase-associated lipocalin, neutrophil elastase, intercellular/vascular cellular adhesion molecules) | between baseline and 3 months | 
| Markers of systemic inflammation | Markers of systemic inflammation will be evaluated at baseline and 3 months after STEMI (high sensitive CRP, IL-1β) | between baseline and 3 months | 
| Neutrophil-driven responses that may further propagate injury | Neutrophil-driven responses that may further propagate injury will be evaluated at baseline and 3 months after STEMI (neutrophil extracellular traps, neutrophil-derived microparticles) | between baseline and 3 months |