A REAl-life Study on Short-term DAPT in Patients With Ischemic Stroke or TIA

Ischemic Stroke Clinical Trial

— READAPT  

Official title:

A REAl-life Study on Short-term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05476081
• Other study ID #: 03/2021
• Status: Recruiting
• Start date: February 3, 2021
• Est. completion date: May 3, 2023

Study information

• Verified date: July 2022
• Source: University of L'Aquila
• Contact: Simona Sacco, MD
• Phone: +390862433561 - +390863499734
• Email: simona.sacco[@]univaq.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack (READAPT) is an observational, multicenter, prospective study involving Italian centers. The study aims at evaluating effectiveness and safety of short-term (21-90 days) dual antiplatelet treatment (DAPT) in secondary prevention of mild-to-moderate ischemic stroke or high-risk TIA.

Description:

The READAPT will depict the benefit/risk profile of DAPT in a clinical setting, and address subgroups of patients such as those with small cerebral vessel diseases or those treated with revascularization procedures.

Randomized clinical trials (RCTs) proved that short-term DAPT is superior over single antiplatelet treatment in reducing the ischemic recurrence risk, without a remarkable increased hemorrhagic risk thanks to the short treatment course. However, RCTs excluded patients treated with revascularization procedures (i.e. intravenous thrombolysis and thrombectomy), did not provide data on neuroimaging, and had slightly different treatment procedures such as time-to-DAPT start and antiplatelets loading dose.

The study comprises a baseline coinciding with the index event, when the investigators will collect demographics and characteristics of the event, and a 90±5 day follow-up from the index event, when patients will be screened for treatment compliance, tolerability and ischemic or hemorrhagic events. Follow-up visit can be performed remotely.

The investigators did not establish strict NIHSS or ABCD2 score cutoff for patients' inclusion, as treatment decision has to be taken independently from the study, and highly recommend physicians to adhere to guidelines. Each participating center will include all consecutive patients (hospitalized or non-hospitalized) who will meet inclusion criteria.

Data were entered in an electronic anonymized database created on the Research Electronic Data Capture (REDCap) software for the analyses hosted at University of L'Aquila. The local PI or the co-investigators will be able to upload patients' data through a single form specifically created for the study, which will include a user-friendly drop-down menu. Anonymized data will be stored on a secured server under the responsibility of University of L'Aquila. The data will be automatically backed-up once a week. Data will not be shared with unauthorized persons. Plausibility of the entered data will be checked by the study manager and the statistical data manger and data queries will be resolved by Local PI. Cases with missing data or unresolved queries will be rejected to retain only the highest quality data in the registry. Data from centers not ensuring consecutive recruitment of patients or adequate follow-up will not be included in the final database.

All analyses will be performed according to the intention-to-treat principle in all included patients completing the 90-day follow-up or having a fatal outcome event within 90 days. Descriptive statistics will be used to report baseline information. The investigators will analyze the time from index event to the first occurrence of primary and secondary outcome events with the use of a Cox proportional hazards model. Two statistical models will be used: Model 1 unadjusted and Model 2 adjusted for demographics and characteristics of the index event. P values for interaction will be calculated according to the following subgroups: type of event (ischemic stroke vs TIA), time to DAPT (≤24 hours vs >24 hours from symptom onset), type of DAPT (aspirin+clopidogrel vs aspirin+ticagrelor), DAPT duration (≤21 vs >21 days and ≤30 vs >30 days), NIHSS score at onset (≤3 vs >3 and ≤5 vs >5), revascularization procedure (i.v. thrombolysis and/or mechanical thrombectomy vs no interventions). Hazard ratios with 95% confidence intervals will be reported. Should multiple events of the same type occur, the time to the first event will be used in the model. Data from patients who had no events during the study will be censored at the time of study termination or death. Assuming a 95% confidence interval, an estimated sample size of 1067 subjects would be required to detect a conservative 50% proportion of primary outcome occurrence with a two-sided 2.5% margin of error.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1067
• Est. completion date: May 3, 2023
• Est. primary completion date: February 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (all to include the patient):

• Patients with mild or moderate non-cardioembolic ischemic stroke or high-risk TIA treated with a short course of DAPT (usually 21-30 days but up to 90-day at the physician's discretion) for the acute event;

• Male or female aged >18 years;

• Providing signed and dated informed consent;

• Willing to comply with all study procedures and to be available for the duration of the study.

Exclusion Criteria (one sufficient to exclude the patient):

• Patients receiving DAPT after endovascular procedures with stenting;

• Patients participating to any interventional RCT on stroke prevention;

• Presence of any condition which may preclude reliability of the collected information

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke
• TIA

Intervention

Drug:
• Aspirin
Aspirin (100-300 mg) administered for 21-90 days in combination with another antiplatelet treatment
• Clopidogrel
Clopidogrel (75-600 mg) administered for 21-90 days in combination with another antiplatelet treatment
• Ticagrelor
Ticagrelor (90-180 mg) administered for 21-90 days in combination with another antiplatelet treatment

Locations

Country	Name	City	State
Italy	Department of Neurology and Stroke Unit, Ente Ecclesiastico ospedale Generale Regionale Miulli	Acquaviva Delle Fonti
Italy	Department f Neurology, AO Nazionale SS Biagio and Cesare Arrigo	Alessandria
Italy	Department of Neurology, Murgia Hospital Fabio Perinei SS 96	Altamura
Italy	Department of Neurology and Stroke Unit Ospedali Riuniti Ancona	Ancona
Italy	Department of Neurology, INRCA-IRCCS "U Sestili" Hospital	Ancona
Italy	Department of Neurology and Stroke Unit, "U. Parini" Hospital	Aosta
Italy	Department of Neurology, San Donato Hospital, Azienda USL Toscana Sud Est, Arezzo e Val D'Arno	Arezzo
Italy	Neurology e Stroke Unit Departement, SS Filippo e Nicola Hospital	Avezzano	Abruzzo
Italy	Department of Neurology and Stroke Unit, "Di Venere" Hospital	Bari
Italy	Stroke Unit, Policlinico di Bari, Giovanni XXIII Hospital	Bari
Italy	Department of Neurology and Stroke Unit, "Mons. Dimiccoli" Hospital	Barletta
Italy	Department of Neurology,San Bassiano Hospital	Bassano Del Grappa
Italy	Stroke Unit, San Martino di Belluno Hospital ULSS 1	Belluno
Italy	Department of Neurology, AO San Pio	Benevento
Italy	Department of Neurology and Stroke Unit, Maggiore Hospital, IRCCS Istituto delle Scienze Neurologiche di Bologna	Bologna
Italy	Department of Neurology, Policlinico S. Orsola-Malpighi-Clinica Neurologica Metropolitana, IRCCS Istituto delle Scienze Neurologiche di Bologna	Bologna
Italy	Stroke Center, Gubbio-Gualdo Tadino Hospital	Branca
Italy	Neuro-vascular Unit, AO Spedali Civili	Brescia
Italy	Stroke Unit, ASST Franciacorta	Brescia
Italy	Stroke Unit, Istituto Ospedaliero Fondazione Poliambulanza	Brescia
Italy	Stroke Unit, A. Perrino Hospital	Brindisi
Italy	Department of Neurology and Stroke Unit, AO "G. Brotzu"	Cagliari
Italy	Department of Neurology and Stroke Unit, S Elia Hospital	Caltanissetta
Italy	Stroke Unit, AO San Sebastiano AORN Caserta	Caserta
Italy	Department of Neurology, San Giacomo Hospital	Castelfranco Veneto
Italy	Department of Neurology, AO Cannizzaro	Catania
Italy	Department of Neurology, Institute G. Giglio di Cefalù	Cefalù
Italy	Department of Neurology and Stroke Unit, "Bufalini" Hospital	Cesena
Italy	Department of Neurology and Stroke Unit, SS Annunziata Hospital	Chieti
Italy	Stroke Center, USL umbria 1	Città di Castello
Italy	Department of Neurology and Stroke Unit, Cittadella, AULSS6 Euganea	Cittadella
Italy	Stroke Unit, Valduce Hospital	Como
Italy	Department of Neurology, Conegliano Hospital Aulss 2 Veneto	Conegliano
Italy	Department of Neurology and Stroke Unit, ASST Maggiore Hospital of Crema	Crema
Italy	Department of Neurology, ASST Cremona	Cremona
Italy	Department of Neurology, Santa Croce Hospital	Cuneo
Italy	Department of Neurology and Stroke Unit, Desio Hospital ASST Monza	Desio
Italy	Department of Neurology, ASUR Area Vasta 4 (ex ZT11)	Fermo
Italy	Department of NeurologY, AOU of Ferrara	Ferrara
Italy	Department of Neurology, San Giovanni di Dio Hospital	Florence
Italy	Stroke Unit, AOU Careggi	Florence
Italy	Department of Neurology, Ente Ospedali Galliera Genova	Genova
Italy	Stroke Unit, San Martino Hospital of Genova	Genova
Italy	Department of Neurology, ASUGI	Gorizia
Italy	Department of Neurology, USL Toscana sud est	Grosseto
Italy	Department of Neurology and Stroke Unit, ASUR Marche AV2 Jesi	Jesi
Italy	Departement of Neurology, San Salvatore Hospital	L'Aquila
Italy	Department of Neuology, Sant'Andrea Hospital, Azienda Sanitaria Locale n. 5 "Spezzino" La Spezia	La Spezia
Italy	Department of Neurology, F Renzetti Hospital	Lanciano
Italy	UTN, Santa Maria Goretti Hospital	Latina
Italy	Department of Neurology, Ospedale Vito Fazi	Lecce
Italy	Department of Neurology, Legnago Hospital	Legnago
Italy	Department of Neurology and Stroke Unit Ospedale of Legnano	Legnano
Italy	Emergency Department, Azienda USL 6 Livorno	Livorno
Italy	Department of Neurology, Valle del Serchio Hospital	Lucca
Italy	Department of Neurology, Apuane Hospital, Azienda USL Toscana Nord Ovest	Massa
Italy	Department of Neurology, ASST Melegnano e della Martesana	Melegnano
Italy	Department of Neurology, ASST Merate	Merate
Italy	Stroke Unit, AOU Gaetano Martino	Messina
Italy	Stroke Unit, Angelo's Hospital	Mestre
Italy	Stroke Unit, Istituto Clinico Città Studi	Milan
Italy	Department of Neurology and Stroke Unit, Humanitas	Milano
Italy	Department of Neurology and Stroke Unit, IRCCS Istituto Auxologico Italiano, San Luca Hospital	Milano
Italy	Department of Neurology, Mirano ULSS 3 Serenissima	Mirano
Italy	Stroke Unit, "S.Agostino-Estense" Hospital, AOU of Modena	Modena
Italy	Stroke Unit, Santa Croce Hospital	Moncalieri
Italy	Department of Neurology, San Gerardo Hospital and Bicocca University	Monza
Italy	Department of Neurology and Stroke Unit, Cardarelli Hospital	Napoli
Italy	Stroke Unit, Ospedale del Mare	Napoli
Italy	Department of Neurology and Stroke Unit, AOU Maggiore della Carità	Novara
Italy	Stroke Unit, San Giacomo Hospital	Novi Ligure
Italy	Stroke Unit, AOU San Luigi Gonzaga	Orbassano
Italy	Stroke Unit, Azienda Ospedale Università	Padova
Italy	Department of Neurology and Stroke Unit, ARNAS Civico of Palermo	Palermo
Italy	Department of Neurology, Villa Sofia Hospital	Palermo
Italy	Department of Neurophysiopathology and Stroke Unit, AOUP Paolo Giaccone	Palermo
Italy	Stroke Unit, Buccheri La Ferla Hospital	Palermo
Italy	Department of neurology, Azienda Ospedaliero-Universitario di Parma	Parma
Italy	Stroke Unit, Fidenza AUSL PR	Parma
Italy	Cerebrovascula disease and Stroke Unit neurological Intitute IRCCS Mondino	Pavia
Italy	Stroke Unit, AOUUD Santa Maria della Misericordia	Perugia
Italy	Department of Neurology ande Stroke Unit, Pescara Hospital	Pescara
Italy	Stroke Unit, Pederzoli Hospital	Peschiera Del Garda
Italy	Department of Neurology, AUSL Piacenza	Piacenza
Italy	Departement of Neurology and Stroke Center, S.Corona Hospital	Pietra Ligure
Italy	Department of Neurology and Stroke Unit, E. Agnelli Hospital	Pinerolo
Italy	Department of Neurology, Azienda ospedaliera e universitaria Pisana	Pisa
Italy	Department of Neurology, San Jacopo Hospital	Pistoia
Italy	Stroke Unit, AO"San Carlo"	Potenza
Italy	Department of Neurology, Maria Paternò Arezzo Hospital	Ragusa
Italy	Department of Neurology and Stroke Unit, Santa Maria delle Croci Hospital	Ravenna
Italy	Stroke Unit, AO "Bianchi-Melacrino-Morelli"	Reggio Calabria
Italy	Department of Neurology and Stroke Unit, Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Department of Neurology, Infermi di Rimini Hospital	Rimini
Italy	Unità di trattamento neurovascolare, Azienda Ospedaliero Universitaria Policlinico Umberto I	Roma
Italy	Department of Neurology and Stroke Unit, Sant'Eugenio Hospital	Rome
Italy	Department of Neurology and Stroke Unit, Systems Medicin, Policlinico Tor Vergata	Rome
Italy	Department of Neurology, Ospedale Fatebenefratelli	Rome
Italy	Department of Neurology, Policlinico Gemelli	Rome
Italy	Department of Neurology, SS Filippo Neri Hospital	Rome
Italy	Stroke Unit, AO San Camillo	Rome
Italy	Stroke Unit, AOU Sant'Andrea	Rome
Italy	Stroke Unit, Ospedale Rovigo, ULSS 18	Rovigo
Italy	Department of Neurology, Presidio ospedaliero Umberto I Nocera Inferiore	Salerno
Italy	Department of Neurology, Madonna del Soccorso Hospital	San Benedetto Del Tronto
Italy	Department of Neurology, ASST Lariana, Sant'Anna Hospital	San Fermo Della Battaglia
Italy	Department of Neurology, Casa sollievo della sofferenza	San Giovanni Rotondo
Italy	Stroke Unit, AOU	Sassari
Italy	Department of Neurology, SS. Annunziata Hospital	Savigliano
Italy	Stroke Unit, Azienda ospedaliera universitaria Senese	Siena
Italy	Department of Neurology and Stroke Unit, Umberto I Hospital	Siracusa
Italy	Department of Neurology, SS Annunziata Hospital	Sulmona
Italy	Department of Neurology and Stroke Unit, AO Santa Maria of Terni	Terni
Italy	Department of Neurology and Stroke Unit, San Giovanni Bosco Hospital	Torino
Italy	Neuro-vascular Unit, Maria Vittoria Hospital	Torino
Italy	Department of Neurology and Stroke Unit, ASP of Trapani	Trapani
Italy	Stroke Unit, Santa Chiara Hospital	Trento
Italy	Department of Neurology, Cà Foncello Hospital	Treviso
Italy	Department of Neurology, Azienda Ospedaliera-Universitaria Giuliano Isontina	Trieste
Italy	Department of Neurology and Rehabilitation, ASUR	Udine
Italy	Department of Neurology and Stroke Unit, ASST Settelaghi	Varese
Italy	Department of Neurology, SS Giovanni e Paolo Hospital, Aulss3 Serenissima Veneto	Venezia
Italy	Department of Neurology, Sant'Andrea Hospital	Vercelli
Italy	Department of Neurology and Stroke Unit, Arzignano Azienda ULSS 8 Berica	Vicenza
Italy	Department of Neurology and Stroke Unit, San Bortolo Hospital	Vicenza
Italy	Stroke Unit, ASST Vimercate	Vimercate
Italy	Department of Neurology and Stroke Unit, Guzzardi Hospital	Vittoria

Sponsors (1)

Lead Sponsor	Collaborator
University of L'Aquila

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y; THALES Investigators. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020 Jul 16;383(3):207-217. doi: 10.1056/NEJMoa1916870. — View Citation

Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-225. doi: 10.1056/NEJMoa1800410. Epub 2018 May 16. — View Citation

Kennedy J, Hill MD, Ryckborst KJ, Eliasziw M, Demchuk AM, Buchan AM; FASTER Investigators. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol. 2007 Nov;6(11):961-9. Epub 2007 Oct 10. — View Citation

Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, Jia J, Dong Q, Xu A, Zeng J, Li Y, Wang Z, Xia H, Johnston SC; CHANCE Investigators. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013 Jul 4;369(1):11-9. doi: 10.1056/NEJMoa1215340. Epub 2013 Jun 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Modified Rankin Scale (mRs)	measure of the disability through a scale from 1 to 6, where 6 indicated death	90 days from DAPT start
Other	Early DAPT discontinuation	Treatment discontinuation due to adverse events, lack of compliance or Diagnosis of atrial fibrillation or other condition requiring anticoagulant treatment	90 days from DAPT start
Primary	Primary composite outcome	Death, stroke recurrence (ischemic or hemorrhagic)	90 days from DAPT start
Secondary	Ischemic stroke		90 days from DAPT start
Secondary	TIA		90 days from DAPT start
Secondary	Intracerebral hemorrhage (ICH)	Lobar or non lobar ICH	90 days from DAPT start
Secondary	Subarachnoid hemorrhage		90 days from DAPT start
Secondary	Other intracranial hemorrhage	Subdural or epidural hematoma	90 days from DAPT start
Secondary	Mild bleeding	bleeding not requiring blood transfusion or causing hemodynamic compromise	90 days from DAPT start
Secondary	Moderate bleeding	bleeding requiring blood transfusion, but not causing hemodynamic compromise	90 days from DAPT start
Secondary	Severe bleeding	bleeding causing hemodynamic compromise and requiring blood transfusion, inotropic support, or surgical intervention and	90 days from DAPT start
Secondary	Myocardial infarction		90 days from DAPT start
Secondary	Hospitalization	hospitalization due to any cause	90 days from DAPT start
Secondary	Death due to vascular causes	Death due to stroke (ischemic or hemorrhagic), systemic hemorrhage, myocardial infarction, congestive heart failure, pulmonary embolism, sudden death, or arrhythmia.	90 days from DAPT start
Secondary	Death due to non-vascular causes	Death due all the other causes (i.e. infections, neoplasms etc)	90 days from DAPT start