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ACT-GLOBAL IA Thrombolysis(ACT-REACT-004)Domain Within the ACT-GLOBAL Adaptive Platform Trial-NCT06352632 (ACT-REACT)

29 de junio de 2026 actualizado por: Dr. Bijoy Menon, University of Calgary

A Multicentre,Prospective,Randomized,Open Label,Blinded-endpoint Trial for Reperfusion Enhancement After Completing Thrombectomy Using Intraarterial Thrombolysis(REACT-IA-Thrombolysis Domain)Embedded in A Multi-faCtorial,mulTi-arm, Multi-staGe,Randomised,gLOBal Adaptive pLatform Trial for Stroke(ACT-GLOBAL) NCT06352632

Study Design and Duration:

This domain will be conducted as part of ACT-GLOBAL platform trial and will have the nested domain name of REACT. It has a prospective, randomised, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design of up to 1,500 subjects with Acute Ischemic Stroke (AIS) who undergo EVT. Randomisation will be stratified by country/ region, and the IA thrombolytic agent (tenecteplase or alteplase). Minimal sufficient balance algorithm will operate within each stratum to preserve balance on key covariates while maintaining allocation randomness.

Participants will be followed for 90 days (or until death, if prior to 90 days). The end of the trial is defined as the date that all participants have completed their Day 90 assessment. Primary outcome data will be determined by simplified, structured method of assessment using the modified Rankin scale (mRS), conducted through centralized telephone interviews or online media performed by central trial personnel blinded to treatment assignment and received.

Domain Interventions:

The intervention group will receive a single dose of local intraarterial thrombolysis using either tenecteplase (at a dose of 0.0625mg/kg; maximum dose of 6.25mg) or alteplase (0.225 mg/kg; maximum dose, 20mg) at the end of EVT procedure plus standard of care while the control group will receive standard of care alone. The selection of the thrombolytic agent will be determined according to local availability. The dose of intraarterial thrombolysis will be increased if the above dose meets prespecified posterior probabilities at the first or second interims.

In all eligible patients:

  1. Local intra-arterial thrombolysis using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg*

  2. No intra-arterial thrombolysis.

    • The dose of IA thrombolysis may be doubled to 0.125 mg/kg tenecteplase or 0.45 mg/kg alteplase if this dose shows futility at pre-specified interims Randomization will be stratified by country/ region, the IA thrombolytic agent used (tenecteplase or alteplase). IA thrombolysis will be administered as a one-time treatment.

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

This is a domain within the ACT-GLOBAL platform trial to compare IA thrombolysis use (Yes vs No) following the completion of endovascular thrombectomy procedures among subjects who did not receive IV thrombolysis.

The key arguments for the proposed trial are:

  • About 50% of patients treated with EVT are left with distal occlusions that cannot be reached with current devices. Even when reperfusion is considered complete, evidence suggests microthrombi persist in downstream cerebral circulation, contributing to poor outcomes.
  • Other approved acute stroke treatments such as intravenous thrombolysis or antithrombotics do not address incomplete reperfusion. Approximately half of stroke patients treated with EVT are not concurrently or pre-treated with IV thrombolysis.
  • Systemic antithrombotics used in conjunction with IV thrombolysis are unsafe or ineffective.
  • Prospective cohorts and randomized controlled trials (RCTs) suggest that targeted intraarterial thrombolysis offered directly to the affected arterial territory is a promising approach to enhance reperfusion when thrombectomy with mechanical devices is complete. Recent meta-analyses from small pilot studies suggest safety of this approach.
  • Recent RCTs showed mixed results but with overall potentially better clinical outcomes with intraarterial thrombolysis using either tenecteplase or alteplase.
  • A high quality, large, pragmatic, and globally representative confirmatory trial is needed to generate definitive evidence and inform clinical practice on the safety and benefit of IA thrombolysis.

Modern endovascular thrombectomy (EVT) offered using mechanical devices like stent-retrievers and aspiration catheters has revolutionized acute stroke therapy and improved outcomes. Still, a significant gap exists between EVT procedural success and clinical recovery in patients with large vessel occlusion stroke. Less than half of patients receiving EVT achieve functional independence (modified Rankin Scale "mRS" 0-2) despite medical care and rehabilitation. Moreover, ~15% of all EVT procedures fail with subsequent dismal outcomes. Incomplete reperfusion is a major reason that explains why many patients fail to recover fully after thrombectomy. This phenomenon occurs either because of clot fragments that lodge in distal arteries (micro-embolization), or because of in-situ thrombus formation in the micro-circulation. These occlusions are too distal for current devices to reach. However, they can be reached in a targeted manner by administering chemical thrombolysis directly into target areas through catheters lodged in large arteries.

While the incidence and consequences of macrocirculatory obstruction are well-described, microcirculatory obstruction (also called no-reflow) has not been extensively studied in stroke. Nonetheless, it has been reported in 25% of patients post successful EVT with associated higher odds of infarct growth, and poor functional outcomes including death. In an imaging sub study of the CHOICE phase II RCT (comparing local intraarterial "IA" alteplase vs placebo following successful thrombectomy), 58% of patients enrolled to the control arm demonstrated persistent hypoperfusion on MRI at 48 hours after successful EVT. This hypoperfusion was postulated to result from microcirculatory obstruction and was associated with poor outcomes.

Intravenous thrombolysis given prior to EVT may have some effect on lysing downstream thrombi once endovascular recanalization is achieved. However, around half of EVT-treated patients do not receive IV thrombolysis due to contraindications or presenting outside IV thrombolysis treatment window. In addition, the short half-life of IV thrombolytic agents (plasma elimination half-life of ~ 3.5 minutes for alteplase and ~20 minutes for tenecteplase) means that they may not have any effect on thrombi that persist after EVT is completed. In a study of 1303 patients from the German stroke registry, patients in whom the IV alteplase infusion was still ongoing at the end of EVT had higher odds of achieving excellent recovery compared to those who completed the infusion prior to EVT completion. Recent RCTs exploring antithrombotics agents to enhance reperfusion either showed harm (IV ASA ( acetylsalicylic acid) with or without IV heparin) or lack of benefit (IV tirofiban).

Targeted intra-arterial (IA) thrombolysis is a promising adjunct therapy that can be offered to enhance reperfusion immediately after EVT. Thrombolysis administered directly in the affected vascular bed maximizes the fibrinolytic effect on the local cerebral circulation while reducing systemic uptake and side effects. Different thrombolytic agents have been used for IA stroke therapy. However, meta-analyses suggest low quality evidence of available studies given their observational nature and restrictive selection criteria. In one meta-analysis of five observational studies (n=269 patients), there was a suggestion of better functional independence with intraarterial alteplase or urokinase over controls (OR: 1.34; 95% CI: 1.00 to 1.80) without increased risk of symptomatic hemorrhage or death. In the INFINITY registry conducted in 10 European centers, IA alteplase was associated with improved reperfusion in 50% of patients who achieved incomplete reperfusion after EVT. The phase II RCT (CHOICE, n=121 subjects) of IA alteplase after successful EVT at a dose equivalent to 25% of the maximum IV alteplase dosing showed the safety and efficacy of this approach. This trial was stopped prematurely due to placebo supply constraints. Still, it showed an absolute risk difference of 18.4% (95%CI 0.3%-36.4%; P=0.047) in excellent outcome (mRS 0-1) favouring IA alteplase, without increased risk of symptomatic intracranial haemorrhage. In an imaging sub study of the trial, 58% of patients enrolled to the control arm demonstrated persistent hypoperfusion on MRI despite angiographically successful EVT. These results need to be interpreted with caution however given small sample size and premature closure of study. A phase III RCT (PEARL, n=324 subjects) with a similar design and IA alteplase dosing as CHOICE was presented recently (unpublished) and showed improved mRS 0-1 in the treatment arm compared to controls with an absolute risk difference of 15% (95%CI 3.7%-26.3%; P=0.01).

Tenecteplase is a promising agent for IA thrombolysis. It has superior pharmacokinetic properties over alteplase including its longer half-life (~20 minutes), and greater fibrin specificity. Our large CIHR (Canadian Institute of Health Research) funded AcT (Alteplase compared to Tenecteplase) RCT (n=1600 subjects) demonstrated the non-inferiority and comparable safety of IV tenecteplase (0.25 mg/kg) vs. alteplase for all ischemic stroke patients eligible for IV thrombolysis. In 520 patients treated with EVT in AcT, there was a suggestion of better recanalization with tenecteplase and similar safety. The EXTENDIA-TNK trial showed superior recanalization and better outcomes among patients treated with IV tenecteplase vs those treated with IV alteplase. Therefore, tenecteplase is now the standard for IV thrombolysis in acute ischemic stroke. The current Canadian Best Practice guidelines recommend tenecteplase as an alternative to alteplase in all eligible stroke patients. Tenecteplase can be administered intraarterially and may help reperfuse the brain better than but as safe as IA alteplase. While two prior RCTs using IA tenecteplase in patients with anterior circulation (POST-TNK, n=540 subjects), and posterior circulation (ATTENTION, N=208 subjects) strokes following endovascular reperfusion showed neutral results, a recent phase III RCT of IA tenecteplase in anterior circulation stroke patients following endovascular reperfusion showed positive results. The ANGEL-TNK trial (n= 255 subjects) was recently presented and showed that patients treated with IA tenecteplase at a dose equivalent to 50% of the IV tenecteplase dose had better 90-day mRS 0-1 compared to controls (40.5% vs 26.4%, OR 1.4, 95%CI 1.1 to 2) without safety concerns.

While these results suggest a potential benefit of IA thrombolysis following thrombectomy, the heterogeneity of existing trials, their narrow geographic scope (conducted primarily in China or Spain), and the inconsistent benefit across key functional outcomes (e.g., improvement in mRS 0-1 but not mRS 0-2 or ordinal shift) underscore the necessity for a globally representative, large-scale, pragmatic confirmatory trial to provide definitive evidence and guide clinical practice.

Domain Rationale:

The key arguments for the proposed trial are:

  • About 50% of patients treated with EVT are left with distal occlusions that cannot be reached with current devices. Even when reperfusion is considered complete, evidence suggests microthrombi persist in downstream cerebral circulation, contributing to poor outcomes.
  • Other approved acute stroke treatments such as intravenous thrombolysis or antithrombotics do not address incomplete reperfusion. Approximately half of stroke patients treated with EVT are not concurrently or pre-treated with IV thrombolysis.
  • Systemic antithrombotics used in conjunction with IV thrombolysis are unsafe or ineffective.
  • Prospective cohorts and randomized controlled trials (RCTs) suggest that targeted intraarterial thrombolysis offered directly to the affected arterial territory is a promising approach to enhance reperfusion when thrombectomy with mechanical devices is complete. Recent meta-analyses suggest safety of this approach.
  • Recent RCTs showed mixed results but with overall potentially better clinical outcomes with intraarterial thrombolysis using either tenecteplase or alteplase. The combination of IV thrombolysis plus IA thrombolysis did not result in safety concerns.
  • A high quality, large, pragmatic, and globally representative confirmatory trial is needed to generate definitive evidence and inform clinical practice on the safety and benefit of IA thrombolysis.

DOMAIN AIMS AND OBJECTIVES

This domain aim is to efficiently, reliably, and simultaneously, determine the effectiveness of targeted intraarterial (IA) thrombolysis using either tenecteplase at a dose of 0.0625mg/kg (maximum dose of 6.25mg) or alteplase (0.225 mg/kg; maximum dose, 20mg) vs. no IA thrombolysis in all patients who undergo EVT. For participants allocated to the IA thrombolysis arm, the selection of thrombolytic agent (tenecteplase or alteplase) will be determined according to local availability.

This domain of the ACT-GLOBAL platform is designed in such a way that the accrued data could be used to design and then ask a future research question on IA thrombolysis in a pertinent subgroup of patients

Tipo de estudio

Intervencionista

Inscripción (Estimado)

1500

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

  • Nombre: Bijoy K Menon, MD
  • Número de teléfono: 403-944-8107
  • Correo electrónico: bkmmenon@ucalgary.ca

Copia de seguridad de contactos de estudio

Ubicaciones de estudio

  • Australia
    • Barangaroo
      • Sydney, Barangaroo, Australia, NSW 2000
        • The George Institute for Global Health
        • Investigador principal:
          • Craig Anderson, MD
        • Contacto:
  • Canadá
    • Alberta
      • Calgary, Alberta, Canadá, T2N2T9
        • University of Calgary- Foothills Medical Centre
        • Contacto:
          • Carol C Kenney, RN
          • Número de teléfono: 403-944-4286
          • Correo electrónico: ckenney@ucalgary.ca
        • Contacto:
        • Investigador principal:
          • Mohammed Almekhlafi, MD
      • Edmonton, Alberta, Canadá
        • University of Alberta
        • Investigador principal:
          • Brian Buck, MD
        • Contacto:
    • British Columbia
      • Kelowna, British Columbia, Canadá
        • Kelowna Regional Hospital
        • Investigador principal:
          • Aleksander Tkach, MD
      • New Westminster, British Columbia, Canadá
        • Royal Columbian Hospital
        • Investigador principal:
          • George Medvedev, MD
        • Contacto:
          • Vishaya Naidoo
      • Vancouver, British Columbia, Canadá
        • University of British Columbia
        • Investigador principal:
          • Thalia Field, MD
        • Contacto:
        • Contacto:
    • Manitoba
      • Winnipeg, Manitoba, Canadá
        • University of Manitoba - Winnipeg Health Science Centre
        • Investigador principal:
          • Nishita Singh, MD
        • Contacto:
    • Ontario
      • Greater Sudbury, Ontario, Canadá
        • Health Sciences North Horizon Sante-Nord
      • Ottawa, Ontario, Canadá
        • Ottawa Civic Hospital
        • Investigador principal:
          • Dariush Dowlatshahi, MD
        • Contacto:
      • Toronto, Ontario, Canadá
        • Sunnybrook Health Science Centre
        • Investigador principal:
          • Richard Swartz, MD
        • Contacto:
    • Quebec
      • Montreal, Quebec, Canadá
      • Sherbrooke, Quebec, Canadá
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canadá
        • Royal University Hospital

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

Inclusion Criteria:

  1. Age ≥18 years
  2. Clinical diagnosis of stroke

Exclusion Criteria:

There are no platform level exclusion criteria.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Único

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Local intra-arterial (IA) thrombolysis using either tenecteplase or alteplase
The intervention group will receive local intra-arterial (IA) thrombolysis using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg.
Biológico: Tenecteplase or Alteplase- depending upon availability at each treating centre
Intra-arterial thrombolysis after endovascular therapy
Otros nombres:
  • Thrombolytic (2 options)
  • tNKase, Metalyse,
  • tPA, Activase
Comparador de placebos: No IA thrombolysis
No intra-arterial thrombolysis.
Otro: Control
No intra-arterial thrombolysis after endovascular therapy

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Una reducción de la dependencia funcional analizada en toda la distribución de resultados evaluados en la Escala de Rankin modificada (mRS),
Periodo de tiempo: Desde la inscripción hasta la evaluación del día 90: los resultados del día 90 se evalúan de forma ciega
Escala de Rankin Modificada (mRS): puntuaciones de 0 a 1 indican un resultado favorable sin o con síntomas pero sin discapacidad, puntuaciones de 2 a 5 indican niveles crecientes de discapacidad (y dependencia) y una puntuación de 6 indica muerte.
Desde la inscripción hasta la evaluación del día 90: los resultados del día 90 se evalúan de forma ciega

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Rate of 90-day mortality
Periodo de tiempo: From enrollment to the Day 90 assessment.
Date and cause of death are collected from randomization until End of Study.
From enrollment to the Day 90 assessment.

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
The Proportion of participants with a Modified Rankin Scale (mRS) of 0-1 at Day 90.
Periodo de tiempo: Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
The Proportion of participants with a Modified Rankin Scale (mRS) of 0-2 at Day 90.
Periodo de tiempo: Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Rating the Health-related quality of life, as measured by the EQ-5D-5L at Day 90.
Periodo de tiempo: Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The version of the instrument selected for the trial is interviewer administered either in-person, or by telemedicine or by telephone. The respondents will also rate their overall health on the day of the interview on a 0-100 visual analogue scale (EQ-VAS).
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Safety Assessments of Serious Adverse Events (SAEs) from enrollment up to Day 4
Periodo de tiempo: From enrollment ( randomization) to the Day 4
Serious Adverse events include the following events :results in death, life threatening,Requires inpatient hospitalization or prolongation of existing hospitalization,Results in persistent disability/incapacity,Is a congenital anomaly/birth defect, an important medical event that may not result in death, be life-threatening, or require hospitalization, but may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed in the SAE selection.
From enrollment ( randomization) to the Day 4
The proportion of patients with Symptomatic intracranial hemorrhage from enrolment up to Day 4
Periodo de tiempo: From enrollment ( randomization) to the Day 4
Any new intracranial hemorrhage detected by brain imaging associated with neurological worsening or deterioration of symptoms.
From enrollment ( randomization) to the Day 4
The proportion of patients with large parenchymal hemorrhage (PH-2) from enrolment up to Day 4
Periodo de tiempo: From enrollment ( randomization) to the Day 4
PH-2:( hemorrhage grading scale) homogeneous hyperdensity occupying over 30% of the infarct zone, with significant mass effect
From enrollment ( randomization) to the Day 4
The Ordinal shift of 7 levels of mRS at 90 days
Periodo de tiempo: Done by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.
Done by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
The Proportion of participants achieving first pass (eTICI 2c or higher) reperfusion (when treated with EVT).
Periodo de tiempo: Completed by the Central Core lab at 30 days after randomization
The thrombolysis in cerebral infarction (TICI) grading system as a tool for determining the response of thrombolytic therapy for ischemic stroke. In neurointerventional radiology it is commonly used for patients post endovascular revascularization.
Completed by the Central Core lab at 30 days after randomization
The Proportion of participants achieving successful recanalization (revised arterial occlusive lesion [rAOL] score of 2b-3) at first angiographic acquisition (when treated with EVT).
Periodo de tiempo: Completed by the Central Core lab at 30 days after randomization
The thrombolysis in cerebral infarction (TICI) grading system as a tool for determining the response of thrombolytic therapy for ischemic stroke. In neurointerventional radiology it is commonly used for patients post endovascular revascularization.
Completed by the Central Core lab at 30 days after randomization
The Ambulatory status at discharge
Periodo de tiempo: Completed at Day 4.
Assessing mobility of the patient at discharge
Completed at Day 4.
The Place of residence at 90 days
Periodo de tiempo: Completed at the Day 90 assessment.
Assessing the patient's residence at the Day 90 follow up. ( example: home,rehabilitation, long term care, remains hospitalized)
Completed at the Day 90 assessment.
Imaging assessment of infarct size and edema volume
Periodo de tiempo: Completed by the Central Core lab at 30 days after randomization
The total absolute infarct volume is the sum of infarct volumes calculated for each slice.
Completed by the Central Core lab at 30 days after randomization
Summative total length of hospital stay in the first 90-days after stroke onset
Periodo de tiempo: Completed at the Day 90 assessment.
Calculating the total number of days the patient was hospitalized since their hospital admission.
Completed at the Day 90 assessment.

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

University of Calgary

Colaboradores

The George Institute for Global Health, Australia

Investigadores

  • Investigador principal: Bijoy K Menon, MD, University Of Calgary
  • Investigador principal: Craig Anderson, MD, The George Institute

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

10 de junio de 2026

Finalización primaria (Estimado)

31 de diciembre de 2030

Finalización del estudio (Estimado)

31 de marzo de 2031

Fechas de registro del estudio

Enviado por primera vez

11 de septiembre de 2025

Primero enviado que cumplió con los criterios de control de calidad

29 de junio de 2026

Publicado por primera vez (Actual)

7 de julio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

7 de julio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

29 de junio de 2026

Última verificación

1 de junio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • ACT REACT-004
  • ACT GLOBAL (Otro identificador: Clinical Trials.gov)

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Descripción del plan IPD

Domain information and tabular trial results will be posted on the National Institutes of Health's website www.clinicaltrials.gov within one year of domain completion.

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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