[SOCRATES -Acute Stroke Or Transient IsChaemic Attack TReated With Aspirin or Ticagrelor and Patient OutcomES]

Summary

The primary objective of the study is to compare the effect of 90-day treatment with ticagrelor (180 mg \[two 90 mg tablets\] loading dose on Day 1 followed by 90 mg twice daily maintenance dose for the remainder of the study) vs acetylsalicylic acid (ASA)-aspirin (300 mg \[three 100 mg tablets\] loading dose on Day 1 followed by 100 mg once daily maintenance dose for the remainder of the study) for the prevention of major vascular events (composite of stroke, myocardial infarction \[MI\], and death) in patients with acute ischaemic stroke or transient ischaemic attack (TIA).

Timeline

Start

2014-01-07

Primary completion

2016-03-02

Completion

2016-03-02

Outcome

Missed primary endpoint

registry Ticagrelor 90 mg vs ASA 100 mg; p = 0.0670; Hazard Ratio (HR) 0.89 (95% CI 0.78 to 1.01) NCT01994720 ↗

paper ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. PMID 27160892 ↗

Publications

• Diener HC, Easton JD, Hart RG, Kasner S, Kamel H, Ntaios G. Review and update of the concept of embolic stroke of undetermined source. Nat Rev Neurol. 2022 Aug;18(8):455-465. doi: 10.1038/s41582-022-00663-4. Epub 2022 May 10.
• Evans SR, Knutsson M, Amarenco P, Albers GW, Bath PM, Denison H, Ladenvall P, Jonasson J, Easton JD, Minematsu K, Molina CA, Wang Y, Wong KL, Johnston SC. Methodologies for pragmatic and efficient assessment of benefits and harms: Application to the SOCRATES trial. Clin Trials. 2020 Dec;17(6):617-626. doi: 10.1177/1740774520941441. Epub 2020 Jul 15.
• Cucchiara B, George DK, Kasner SE, Knutsson M, Denison H, Ladenvall P, Amarenco P, Johnston SC. Disability after minor stroke and TIA: A secondary analysis of the SOCRATES trial. Neurology. 2019 Aug 13;93(7):e708-e716. doi: 10.1212/WNL.0000000000007936. Epub 2019 Jul 11.
• Easton JD, Denison H, Evans SR, Knutsson M, Amarenco P, Albers GW, Ladenvall P, Minematsu K, Molina CA, Wang Y, Wong KL, Johnston SC; SOCRATES Steering Committee and Investigators. Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial. Int J Stroke. 2019 Dec;14(9):908-914. doi: 10.1177/1747493019851282. Epub 2019 May 15.
• Molina CA, Johnston SC, Ladenvall P, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Knutsson M, Minematsu K, Rother J, Wang Y, Wong KSL; SOCRATES Steering Committee and Investigators. Time to Loading Dose and Risk of Recurrent Events in the SOCRATES Trial. Stroke. 2019 Mar;50(3):675-682. doi: 10.1161/STROKEAHA.118.022675.
• Wong KSL, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Himmelmann A, Kasner SE, Knutsson M, Ladenvall P, Minematsu K, Molina CA, Wang Y, Johnston SC; SOCRATES Steering Committee and Investigators. Efficacy and Safety of Ticagrelor in Relation to Aspirin Use Within the Week Before Randomization in the SOCRATES Trial. Stroke. 2018 Jul;49(7):1678-1685. doi: 10.1161/STROKEAHA.118.020553. Epub 2018 Jun 18.
• Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Hill MD, Jonasson J, Kasner SE, Ladenvall P, Minematsu K, Molina CA, Wang Y, Wong KSL, Johnston SC; SOCRATES Steering Committee and Investigators. Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source. Stroke. 2017 Sep;48(9):2480-2487. doi: 10.1161/STROKEAHA.117.017217. Epub 2017 Jul 18.
• Easton JD, Aunes M, Albers GW, Amarenco P, Bokelund-Singh S, Denison H, Evans SR, Held P, Jahreskog M, Jonasson J, Minematsu K, Molina CA, Wang Y, Wong KSL, Johnston SC; SOCRATES Steering Committee and Investigators. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes). Circulation. 2017 Sep 5;136(10):907-916. doi: 10.1161/CIRCULATIONAHA.117.028566. Epub 2017 Jun 27.
• Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Hill MD, Jonasson J, Kasner SE, Ladenvall P, Minematsu K, Molina CA, Wang Y, Wong KSL, Johnston SC; SOCRATES Steering Committee and Investigators. Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. Lancet Neurol. 2017 Apr;16(4):301-310. doi: 10.1016/S1474-4422(17)30038-8. Epub 2017 Feb 23.
• Wang Y, Minematsu K, Wong KS, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Jonasson J, Molina CA, Johnston SC; SOCRATES Steering Committee and Investigators. Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients: From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes). Stroke. 2017 Jan;48(1):167-173. doi: 10.1161/STROKEAHA.116.014891. Epub 2016 Nov 29.
• Held P, Himmelmann A, Ditmarsch M. Ticagrelor for the treatment of atherosclerotic disease: insights from the PARTHENON clinical development program. Future Cardiol. 2016 Jul;12(4):405-18. doi: 10.2217/fca-2016-0028. Epub 2016 May 10.
• Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Jonasson J, Minematsu K, Molina CA, Wang Y, Wong KS; SOCRATES Steering Committee and Investigators. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Jul 7;375(1):35-43. doi: 10.1056/NEJMoa1603060. Epub 2016 May 10.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Aspirin	Small molecule	100 mg	Oral
Subject	Ticagrelor	Small molecule	90 mg	Oral

Indications