ACS - Acute Coronary Syndrome, Anti-Bacterial Agents, Blood Platelets, Drug Effects, Drug Resistance, Dysbiosis, Microbiota, Myocardial Infarction (MI), Platelet Aggregation, Platelet Aggregation Inhibitors, Platelet Function Tests, Rifaximin, Ticagrelor
Conditions
Keywords
high platelet reactivity, HPR, Multiplate aggregometry, multiple electrode aggregometry, MEA, microbiome, gut flora, eubiotic, 16S rRNA sequencing, P2Y12 inhibitor
Brief summary
The FLORA-ACS study aims to evaluate the relationship between dysbiosis and high platelet reactivity during treatment with ticagrelor in patients with a history of acute coronary syndromes and investigate the use of rifaximin to eliminate dysbiosis and thus provide effective antiplatelet treatment.
Detailed description
A research hypothesis has been formulated indicating dysbiosis of the gut microbiota as a possible cause of high platelet reactivity (HPR) during treatment with an antiplatelet agent, ticagrelor, in post-acute coronary syndrome (ACS) patients. The use of rifaximin, an antibiotic exhibiting an eubiotic effect, may correct gut dysbiosis and help determine whether changes in the microbiota influence HPR. The FLORA-ACS study will enroll 50 subjects with a history of ACS treated with ticagrelor (standard maintenance dose of 90 mg orally twice a day) and characterized by HPR. Participants will be enrolled in the study no sooner than 1 month and no later than 12 months following the ACS incident. Platelet activity will be tested using the multiple electrode aggregometry method (Multiplate analyzer) with the HPR defined based on the consensus paper of the Working Group on On-Treatment Platelet Reactivity. Concurrently, fecal samples will be collected for microbiome profiling. The microbiota will be analyzed in terms of fecal bacterial richness and diversity using 16S ribosomal RNA sequencing. Participants will receive a 7-day course of oral rifaximin (400 mg every 12 hours). Both platelet activity and microbiota testing will be conducted at baseline and post-treatment. Additional laboratory testing will include complete blood count and C-reactive protein. An analysis of major adverse cardiovascular events (MACE) occurrence within a 6-month follow-up period is planned.
Interventions
DRUGRifaximin
Participants receiving a 7-day course of oral rifaximin 400 mg every 12 hours
Sponsors
Ministry of Science and Higher Education, Poland
Collegium Medicum w Bydgoszczy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Between 18 and 80 years of age * History of acute coronary syndrome no sooner than 1 month and no later than 12 months prior to study inclusion * Current treatment with ticagrelor (90 mg orally twice a day) * High platelet reactivity assessed with multiple electrode aggregometry method (AUC of \>46 U) * Provision of informed consent prior to any study procedures
Exclusion criteria
* History of hypersensitivity to rifaximin or other rifamycin-derived agent * Ongoing treatment with rifamycins * Platelet count \< 100×10\^9/L or \> 450×10\^9/L * Treatment with antibiotics, probiotics, or glucocorticoids within 3 months prior to study inclusion * History of gastrointestinal diseases such as inflammatory bowel disease, bowel obstruction, or gastrointestinal tumor * Infection, including gastrointestinal infection, within a month prior to study inclusion * History of Clostridium difficile infection * Current use of specific medications (warfarin, glycoprotein IIb/IIIa inhibitors, immunosuppressants, bile acid sequestrants, antidiarrheal agents) * Impaired liver function classified as Child-Pugh class B or C * Hemodynamic instability * Pregnancy or breastfeeding * Patients considered by the investigator to be uncooperative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in platelet reactivity in Multiplate | 0-7 days | Relative reduction in platelet reactivity from baseline to post-intervention by \>10%, assessed with Multiplate analyzer (multiple electrode aggregometry) |
| Achievement of platelet reactivity below HPR | 0-7 days | Achieving platelet reactivity below HPR in a patient with a higher baseline value, assessed with Multiplate analyzer (multiple electrode aggregometry) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative reduction in platelet reactivity in thromboelastography | 0-7 days | Relative reduction in platelet reactivity from baseline to post-intervention by \>10%, assessed with Platelet Mapping assay (thromboelastography) |
| Relative reduction in platelet reactivity | 0-7 days | Relative reduction in platelet reactivity from baseline to post-intervention by \>10%, assessed with VerifyNow P2Y12 assay |
| Changes in microbiome profile | 0-7 days | Changes in microbiome profile post-intervention assessed using 16S rRNA sequencing |
| Achieving platelet reactivity below HPR in thromboelastography | 0-7 days | Achieving platelet reactivity below HPR in a patient with a higher baseline value, assessed with Platelet Mapping assay (thrombelastography) |
| Achieving platelet reactivity below HPR in VerifyNow | 0-7 days | Achieving platelet reactivity below HPR in a patient with a higher baseline value, assessed with VerifyNow P2Y12 assay |
Countries
Poland
Contacts
Primary ContactKlaudyna Grzelakowska, MD
Outcome results
None listed