CLEAR SYNERGY Neutrophil Substudy

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

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:

1. Evaluation of markers of neutrophil activity at randomization (baseline) and 3 months follow-up in the colchicine versus placebo groups, and;
2. 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:

1. Assess the effect of colchicine on neutrophil activation in response to STEMI.
2. Examine clinical and genetic factors that determine heterogeneity of treatment response anddistinguish colchicine responders from non- responders.
3. 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.

Study Overview

• Status: Active, not recruiting
• Conditions: STEMI - ST Elevation Myocardial Infarction; Neutrophils.Hypersegmented | Bld-Ser-Plas
• Intervention / Treatment: Drug: Colchicine Pill

• Study Type: Observational
• Enrollment (Actual): 322

Contacts and Locations

• Study Contact: Name: Fatmira Curovic; Phone Number: 347-602-2934; Email: fatmira.curovic@nyumc.org
• Study Contact Backup: Name: Binita Shah, MD

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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. These are patients who present with STEMI.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Placebo	Drug: Colchicine Pill; 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.
Colchicine	Drug: Colchicine Pill; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Population Health Research Institute
• Investigators: Principal Investigator: Binita Shah, MD, NYU School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2019
• Primary Completion (Actual): February 20, 2023
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 14, 2019

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 18-01323; 1R01HL146206 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No