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Patients with tandem lesions (TL) are defined as patients with an acute ischemic stroke (AIS) with occlusion of an intracranial vessel of the anterior circulation and an occlusion or severe stenosis (70-99%) of the origin of the ipsilateral internal carotid artery (ICA). The greatest current limitation in the management of this type of lesion is the use of antithrombotic medication (double antiaggregation) in the acute phase that is required in case of placing extracranial stent to stabilize the atheroma plaque. In relation to this antiplatelet regimen, the latest clinical practice guidelines warn about the risk of combining intravenous fibrinolysis with antiplatelet medication in the acute phase, since it seems to increase the risk of symptomatic intracranial hemorrhage (sICH). However, the non-stabilization of the carotid atheroma plaque is associated with higher rates of cervical reocclusion, poorer functional prognosis, and higher mortality.
Therefore, the use of a single antiplatelet agent could be a reasonable alternative. To establish the best protocol for mono-antiaggregant therapy in the acute phase of TL, the investigators propose to carry out a prospective multicenter randomized clinical trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tirofiban | Experimental | An intravenous bolus of 500 micrograms of Tirofiban will be intravenously administered in five minutes with an infusion pump (infusion rate: 120 milliliters / hour), which is equivalent to 10 ml (500 micrograms) of Tirofiban. After five minutes, a dose reduction will be programmed to 200 micrograms / hour (infusion rate: 4 milliliters / hour for 24 hours (maximum total infused dose of 96 milliliters). |
|
| Acetylsalicylic acid | Active Comparator | A single dose 500 milligrams of Acetylsalicylic acid (ASPIRINA®, 500 mg) will be intravenously administered. One vial of ASPIRINA ® in not more than 250 ml in 0.9% sodium chloride solution, 5% and 10% glucose solution, Ringer's solution or lactated Ringer's. The solution for injection should be prepared on the spot and used immediately after preparation. It is highly recommended to administer as soon as possible after femoral puncture and always before stent placement, allowing a 10-minute delay after placement of the cervical endoprosthesis. In case of exceeding this time, the patient will be withdrawn from the trial. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tirofiban | Drug | An intravenous bolus of 500 micrograms of Tirofiban will be intravenously administered in five minutes with an infusion pump (infusion rate: 120 milliliters / hour), which is equivalent to 500 micrograms of Tirofiban. After five minutes, a dose reduction will be programmed to 200 micrograms / hour (infusion rate: 4 milliliters / hour for 24 hours (maximum total infused dose of 96 milliliters). Tirofiban infusion started in the neuroradiology room should be maintained until a control brain computerized tomography (CT) scan is performed at 20 hours (+/-2 hours). Once the absence of parenchymal hematoma is demonstrated in control CT, loading doses of acetylsalicylic acid and clopidogrel will be intravenously administered in the Tirofiban group, and the perfusion must be maintained simultaneously of Tirofiban and oral double antiplatelet therapy for four hours, after which the administration of the experimental drug should be discontinued. |
| Measure | Description | Time Frame |
|---|---|---|
| Carotid Reocclusion | Outcome measure assessment will be performed using ultrasound doppler, in which carotid reocclusion is define by:
| Annually (single evaluation): within the first 24 hours (+/- 12hours) |
| Platelet aggregation phenomena | Outcome measure assessment will be performed using ultrasound doppler, in which carotid reocclusion is define by:
| Annually (single evaluation): within the first 24 hours (+/- 12hours) |
| Symptomatic intracranial hemorrhage (sICH) | The sICH is defined as a new intracranial hemorrhage in brain computerized tomography within hospitalization related to an National institute of Health Stroke Scale score increase >4 points compared with stroke admission. | Within first 24 hours after inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| Good functional prognosis | Defined as a score on the modified rankin scale (mRS) between 0-2 at 90 days. | At 90 days (+/- 7 days) after inclusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elena Zapata-Arrizada, PhD | Virgen del Rocío Hospital, Seville, Spain | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Complexo Hospitalario Universitario A Coruña | A Coruña | A Coruña | Spain | |||
| General Hospital Dr. Balmis (Alicante) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38195586 | Derived | Zapata-Arriaza E, Medina-Rodriguez M, Moniche Alvarez F, de Alboniga-Chindurza A, Aguilar-Perez M, Ainz-Gomez L, Baena-Palomino P, Zamora A, Pardo-Galiana B, Delgado-Acosta F, Valverde Moyano R, Jimenez-Gomez E, Bravo Rey I, Oteros Fernandez R, Escudero-Martinez I, Vielba-Gomez I, Morales Caba L, Diaz Perez J, Garcia Molina E, Mosteiro S, Castellanos Rodrigo MDM, Amaya Pascasio L, Hidalgo C, Freijo Guerrero MDM, Gonzalez Diaz E, Ramirez Moreno JM, Fernandez Prudencio L, Terceno Izaga M, Bashir Viturro S, Gamero-Garcia MA, Jimenez Jorge S, Rosso Fernandez C, Montaner J, Gonzalez Garcia A. Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial). Trials. 2024 Jan 9;25(1):35. doi: 10.1186/s13063-023-07817-9. |
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|
| Acetylsalicylic acid | Drug | A single dose 500 milligrams of Acetylsalicylic acid (ASPIRINA®, 500 mg) will be intravenously administered. The solution for injection should be prepared on the spot and used immediately after preparation. It is highly recommended to administer as soon as possible after femoral puncture and always before stent placement, allowing a 10-minute delay after placement of the cervical endoprosthesis. In case of exceeding this time, the patient will be withdrawn from the trial. It will not be necessary to maintain aspirin infusion. In the Acetylsalicylic acid group, a head computerized tomography scan will also be performed at 20 (+/- 2 hours) after the endovascular procedure. Once the absence of parenchymal hematoma is demonstrated, a load of clopidogrel and 100 mg of Acetylsalicylic acid will be administered. Oral antiplatelet medication can be administered orally if the patient has a good level of consciousness and is not associated with dysphagia; or by placing a nasogastric tube. |
|
| Alicante |
| Alicante |
| Spain |
| Complejo Hospitalario Torrecárdenas | Almería | Almería | Spain |
| Complejo Hospital Universitario de Badajoz | Badajoz | Badajoz | Spain |
| Germans Trias i Pujol Hospital | Badalona | Barcelona | Spain |
| Hospital Universitario de Cruces | Bilbao | Bilbao | Spain |
| Reina Sofía Hospital | Córdoba | Córdoba | Spain |
| Josep Trueta Hospital | Girona | Gerona | Spain |
| Ramón y Cajal Hospital | Madrid | Madrid | Spain |
| Hospital Clínico Universitario Virgen de la Arrixaca, Murcia | Murcia | Murcia | Spain |
| Virgen del Rocío Hospital | Seville | Seville | Spain |
| Virgen Macarena Hospital | Seville | Seville | Spain |
| Hospital Universitario y Politécnico de La Fe | Valencia | Valencia | Spain |
| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077466 | Tirofiban |
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D014443 | Tyrosine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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