Clopidogrel vs. Aspirin for Cardiovascular Risk Reduction in Patients With S. Aureus Bacteremia (Clopido-SNAP 2)

This is an open-label randomized controlled trial which will enroll patients with S. aureus bacteremia who are already taking aspirin for secondary prevention of cardiovascular events. We will randomize patients to continue their aspirin or change clopidogrel which is also approved for secondary prevention.

Unlike aspirin, clopidogrel may have activity against S. aureus. We wish to determine if changing to clopidogrel will improve outcomes in S. aureus bacteremia in people who otherwise would have a reason to be taking it.

This study is an approved sub-study of The Staphylococcus aureus Network Adaptive Platform (SNAP) trial (NCT05137119).

If positive, this study will support a Phase 3 RCT in people who do not currently have an indication for clopidogrel.

Study Overview

• Status: Recruiting
• Conditions: Staphylococcus Aureus Endocarditis; Staphylococcus Aureus Septicemia; Staphylococcus Aureus Bloodstream Infection
• Intervention / Treatment: Drug: Clopidogrel; Drug: Aspirin

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lina Petrella; Phone Number: 23730 5149341934; Email: lina.petrella@muhc.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A3S1
      • Recruiting
      • McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital)
      • Principal Investigator: Emily G McDonald, MD MSc
      • Principal Investigator: Todd C Lee, MD MPH FIDSA
      • Sub-Investigator: Alexander Lawandi, MD MSc
      • Contact: Lina Petrella; Phone Number: 23730 514-934-1934; Email: lina.petrella@muhc.mcgill.ca
      • Sub-Investigator: Matthew P. Cheng, MD SM
      • Sub-Investigator: Patrick Lawler, MD MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

The participant must meet all inclusion and exclusion criteria for the SNAP

Platform (NCT05137119) and also the following inclusion and exclusion criteria:

Inclusion Criteria:

• Patient is taking aspirin for secondary prevention of cardiovascular disease (coronary, cerebrovascular, or peripheral vascular disease)

Exclusion Criteria:

• Active bleeding (allowing up to 3 days from platform entry to randomize in the event anti-thrombotic therapy is resumed)
• Anticipated major cardiac surgery, neurosurgery, or spine surgery within the next 3 days
• Pregnancy
• Known receipt of clopidogrel, prasugrel, or ticagrelor within the last month
• Allergy to clopidogrel
• Concomitant receipt of oral Xa inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Change to clopidogrel; Patients will have their aspirin discontinued and start clopidogrel.	Drug: Clopidogrel; Patients will change from aspirin to clopidogrel (without loading dose)
Active Comparator: Continue aspirin; Patients will continue their existing aspirin	Drug: Aspirin; Patients will continue their existing aspirin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Desirability of Outcome Ranking (DOOR)	Desirability of Outcome Ranking (DOOR) - an ordinal outcome with 5 levels defined: Rank 1 - Alive without complication Rank 2 - Alive with 1 complication Rank 3 - Alive with 2 complications Rank 4 - Alive with 3 complications Rank 5 - Dead Complications include: Clinical failure: Absence of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated.; Infectious Complications: Including new endocarditis; new evidence of other deep metastatic foci (e.g., osteomyelitis or deep abscess); relapse of MRSA bacteremia after a patient has sterilized their initial blood cultures; readmission for subsequent care of S. aureus bacteremia; need for unplanned source control procedures; Serious adverse drug event (Common Terminology Criteria class 4) due to study drug OR adverse drug event (classes 1-3) leading to discontinuation of the study drug	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Event or Adverse Event Leading to Discontinuation	Defined as a serious adverse drug event (Common Terminology Criteria for Adverse Events (CTCAE) class 4) presumed due to study drug OR adverse drug event (CTCAE classes 1-3) leading to discontinuation of the study drug	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
All cause mortality	Death from any cause	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Infectious Complications	Defined as change in therapy for inadequate clinical response; new endocarditis; new evidence of other deep metastatic foci (e.g., osteomyelitis or deep abscess); relapse of MRSA bacteremia after a patient has sterilized their initial blood cultures; readmission for subsequent care of S. aureus bacteremia; need for unplanned source control procedures. New implies that the complication was not suspected at enrollment and is not a function of delay to diagnostic testing.	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Clinically relevant major bleeding	This will be defined according to the criteria of the International Society on Thrombosis and Haemostasis as one or more of the following: fatal bleeding; symptomatic bleeding in a critical area or organ (including hemorrhagic stroke); bleeding that causes a fall in hemoglobin level of ≥20 g/L; or bleeding that requires a transfusion of 2 or more units of whole blood or red cells. For bleeds into non-critical areas, we will also record the site of bleeding.	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Clinically relevant venous thromboembolic events	This will be defined as an acute objectively confirmed deep vein thrombosis (upper extremity, lower extremity, other such as portal vein, cerebral vein, splanchnic vein) and/or segment or proximal pulmonary embolism, which is symptomatic and/or necessitates specific treatment. Below knee DVT and superficial thrombophlebitis are not included. Pulmonary embolism needs to be, segmental or proximal. Subsegmental pulmonary embolisms are not included as they have poor interrater reliability and may represent artefact in up to 50% of cases.	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Clinically relevant stroke	Stroke is defined as the acute onset of focal neurological dysfunction caused by brain, spinal cord, or retinal vascular injury because of infarction (ischemia). Ideally, at least one of the following should be present to confirm the diagnosis of stroke: confirmation by neurology, stroke specialist, or neurosurgical specialist, brain imaging (e.g., CT scan, MRI scan, or cerebral vessel angiography compatible with acute ischemia). If the acute focal signs represent a worsening of a previous deficit, these signs must persist for more than 24 hours and be accompanied by an appropriate new MRI or CT scan finding. In the absence of neuroimaging, a staff neurologist consult which makes the diagnosis of stroke will be considered.	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Clinically relevant acute myocardial infarction	Patients with S. aureus bacteremia often have substantial physiological stresses which can be associated with rises in cardiac troponin (demand ischemia). For the purposes of this outcome, acute myocardial infarction is captured as a type 1 myocardial infarction: detection of rise and/or fall of cardiac biomarkers with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia. For the purposes of this pragmatic trial, such a myocardial infarction will be inferred from the opinions of the staff cardiologist, intensivist, or general internal medicine specialist. The peak troponin value will be recorded, and a redacted copy of the relevant consultant's note and ECGs will be uploaded for audit.	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Clinically relevant arterial thromboembolic event	Clinical history compatible with sudden worsening of end organ or limb perfusion and confirmation by imaging (e.g., CT angiography, arterial doppler) or need for urgent surgery or thrombolysis.	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)
Clinical Failure	Defined as the absence of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment.	Day 90 post enrollment in the S. aureus Network Adaptive Platform Trial (NCT05137119)

Collaborators and Investigators

• Sponsor: Todd C. Lee MD MPH FIDSA
• Investigators: Principal Investigator: Emily G McDonald, MD MSc, Research Institute of the McGill University Health Centre; Principal Investigator: Todd C Lee, MD MPH FIDSA, Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• Gentry CA, Williams RJ 2nd, Whitman CM, Thind SK, Kliewer BS. Staphylococcus aureus bacteraemia treatment outcomes in patients receiving ticagrelor vs a propensity-matched cohort receiving clopidogrel. Int J Antimicrob Agents. 2023 Apr;61(4):106743. doi: 10.1016/j.ijantimicag.2023.106743. Epub 2023 Feb 2.
• Caffrey AR, Appaneal HJ, LaPlante KL, Lopes VV, Ulloa ER, Nizet V, Sakoulas G. Impact of Clopidogrel on Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: a National Retrospective Cohort Study. Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0211721. doi: 10.1128/aac.02117-21. Epub 2022 Apr 13.
• Tong SYC, Mora J, Bowen AC, Cheng MP, Daneman N, Goodman AL, Heriot GS, Lee TC, Lewis RJ, Lye DC, Mahar RK, Marsh J, McGlothlin A, McQuilten Z, Morpeth SC, Paterson DL, Price DJ, Roberts JA, Robinson JO, van Hal SJ, Walls G, Webb SA, Whiteway L, Yahav D, Davis JS; Staphylococcus aureus Network Adaptive Platform (SNAP) Study Group. The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe. Clin Infect Dis. 2022 Nov 30;75(11):2027-2034. doi: 10.1093/cid/ciac476.

Helpful Links

• Main Website for the S. aureus Network Adaptive Platform Trial (SNAP)

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: October 18, 2024
• First Submitted That Met QC Criteria: October 18, 2024
• First Posted (Actual): October 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: clopidogrel; aspirin; S. aureus bloodstream infection; S. aureus endocarditis; S. aureus bactremia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Sepsis; Bacteremia; Endocarditis; Staphylococcal Infections; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Thiophenes; Salicylates; Hydroxybenzoates; Ticlopidine; Thienopyridines; Clopidogrel; Aspirin
• Other Study ID Numbers: 2025-10899; 500048 (Other Grant/Funding Number: Canadian Institutes of Health Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data sharing policies are dependent on the policies of the SNAP Platform (NCT05137119)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No