Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)

NCT01422616 | Completed Phase 3 DMC

• 1 other identifier: X11-0123
• Study Type: interventional
• Target: 4,587
• Locations: 1 country
• Sites: 1

Brief Summary

ENCHANTED is an independent, investigator initiated, international collaborative, quasi-factorial randomised controlled trial involving a package of 2 linked comparative randomised treatment arms, which aims to address 4 key questions in patients eligible for thrombolysis in the acute phase of ischaemic stroke. (1) Does low-dose (0.6 mg/kg) intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) provide equivalent benefits compared to standard-dose (0.9 mg/kg) rtPA? (2) Does intensive blood pressure (BP) lowering (130-140 mmHg systolic target) improve outcomes compared to the current guideline recommended level of BP control (180 mmHg systolic target)? (3) Does low-dose (0.6 mg/kg) intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) reduce the risk of symptomatic intracerebral haemorrhage (sICH)? (4) Does the addition of intensive BP lowering to thrombolysis with rtPA reduce the risk of any intracerebral haemorrhage (ICH)? The rtPA dose arm of the study addressing questions (1) and (3) concluded with a publication of the results in May 2016. The BP intensity arm of the study addressing questions (2) and (4) concluded with a publication of the results in February 2019.

Conditions

Ischemic Stroke; High Blood Pressure

Keywords

Ischemic stroke; High blood pressure; Thrombolysis; Antihypertensive drugs; Disability; Clinical trial

Outcome Measures

Primary Outcomes (1)

• Combined death and disability

  Unadjusted modified Rankin Scale \[mRS\] score 2-6

  90 days

Secondary Outcomes (16)

• Symptomatic intracerebral hemorrhage

  36 hours

• Symptomatic intracerebral hemorrhage

  36 hours

• Death or disability by the alternative, ordinal shift analysis

  90 days

• Death

  at 7 and 90 days

• Disability

  90 days

Study Arms (4)

Low-dose rtPA (Recruitment completed in August 2015)

EXPERIMENTAL

low-dose 0.6 mg/kg (maximum of 60 mg) i.v. rtPA

Drug: Low-dose rtPA

Standard-dose rtPA (Recruitment completed in August 2015)

ACTIVE COMPARATOR

standard-dose 0.9 mg/kg (maximum of 90 mg) i.v. rtPA

Drug: Standard-dose rtPA

Early intensive BP lowering

EXPERIMENTAL

The trial is an assessment of BP lowering management strategies, using routinely available drugs. Intensive blood pressure (BP) lowering to a target systolic BP range 130-140 mmHg within one hour and to maintain this level for at least 72 hours (or until hospital discharge or death if this should occur earlier). A standardised i.v. BP lowering regimen using locally available and approved i.v. BP lowering agents (e.g. Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol Trinitrate, Phentolamine mesylate, Nicardipine, Urapidil, Esmolol, Clonidine, Enalaprilat, Nitroprusside) will be used, commenced in the emergency department and later in a high dependency area (e.g. acute stroke or neurointensive care unit) as is usual for patients receiving rtPA.

Other: Intensive blood pressure (BP) lowering

Control / guideline-based BP management

ACTIVE COMPARATOR

The trial is an assessment of BP lowering management strategies, using routinely available drugs. Patients allocated to the control group will receive management of BP that is based on a standard guideline, as published by the American Heart Association (AHA). For this group, the attending clinician may consider commencing BP treatment if the systolic level is greater than 180 mmHg, however and the first line treatment will be oral (including nasogastric if required) and/or transdermal routes. Should control of systolic BP not be achieved via these routes, i.v. treatment may be started until the target systolic BP of 180 mmHg is achieved.

Other: BP management policies

Interventions

Low-dose rtPA DRUG

Patients allocated to low-dose will receive 0.6 mg/kg (maximum of 60 mg) i.v. (15% bolus \[maximum bolus dose of 9mg\] and 85% infusion over 60 mins) recombinant tissue plasminogen activator (rtPA).

Also known as: Actilyse

Low-dose rtPA (Recruitment completed in August 2015)

Standard-dose rtPA DRUG

Patients allocated to standard-dose will receive 0.9 mg/kg (maximum of 90 mg) i.v. (10% bolus and 90% infusion over 60 mins) rtPA.

Also known as: Actilyse

Standard-dose rtPA (Recruitment completed in August 2015)

Intensive blood pressure (BP) lowering OTHER

Intensive blood pressure (BP) lowering to a target systolic BP range 130-140 mmHg within one hour and to maintain this level for at least 72 hours (or until hospital discharge or death if this should occur earlier). A standardised i.v. BP lowering regimen using locally available and approved i.v. BP lowering agents will be used, commenced in the emergency department and later in a high dependency area (e.g. acute stroke or neurointensive care unit) as is usual for patients receiving rtPA. The trial is an assessment of BP lowering management strategies, using routinely available drugs. There is some flexibility in the use of particular BP lowering agents to achieve BP targets.

Also known as: Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol Trinitrate, Phentolamine mesylate, Nicardipine, Urapidil, Esmolol, Clonidine, Enalaprilat, Niroprusside

Early intensive BP lowering

BP management policies OTHER

Patients allocated to the control group will receive management of BP that is based on a standard guideline, as published by the AHA. For this group, the attending clinician may consider commencing BP treatment if the systolic level is greater than 180 mmHg, however and the first line treatment will be oral (including nasogastric if required) and/or transdermal routes. Should control of systolic BP not be achieved via these routes, i.v. treatment may be started until the target systolic BP of 180 mmHg is achieved. The trial is an assessment of BP lowering management strategies, using routinely available drugs. There is some flexibility in the use of particular BP lowering agents to achieve BP targets.

Also known as: Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol Trinitrate, Phentolamine mesylate, Nicardipine, Urapidil, Esmolol, Clonidine, Enalaprilat, Niroprusside

Control / guideline-based BP management

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (age ≥18 years)
• A clinical diagnosis of acute ischaemic stroke confirmed by brain imaging
• Able to receive treatment within 4.5 hours after the definite time of onset of symptoms
• Have a systolic BP ≤185 mmHg
• Provide informed consent (or via an appropriate proxy, according to local requirements)
• Specific criteria for arm \[A\] of low-dose vs standard-dose rtPA (Recruitment completed in August 2015.):
• Able to receive either low-dose or standard-dose rtPA
• Specific criteria for arm \[B\] of intensive BP lowering vs guideline recommended BP control
• Patient will or has received thrombolysis treatment with rtPA, either randomised dose within the trial or physician decided dose rtPA outside of the trial
• Sustained elevated systolic BP level, defined as 2 readings ≥ 150 mmHg
• Able to commence intensive BP lowering treatment within 6 hours of stroke onset
• Able to receive either immediate intensive BP lowering or conservative BP management

You may not qualify if:

• Unlikely to potentially benefit from the therapy (e.g. advanced dementia), or a very high likelihood of death within 24 hours of stroke onset.
• Other medical illness that interferes with outcome assessments and follow-up \[known significant pre-stroke disability (mRS scores 2-5)\].
• Specific contraindications to rtPA (Actilyse) or any of the blood pressure agents to be used.
• Participation in another clinical trial involving evaluation of pharmacological agents.
• Need for following concomitant medication, including phosphodiesterase inhibitors and monoamine oxidase inhibitors.

Sponsors & Collaborators

• The George Institute: lead
• National Health and Medical Research Council, Australia: collaborator
• The Stroke Association, United Kingdom: collaborator
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Takeda: collaborator

Study Sites (1)

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Related Publications (32)

• Anderson CS, Woodward M, Arima H, Chen X, Lindley RI, Wang X, Chalmers J; ENCHANTED Investigators. Statistical analysis plan for evaluating low- vs. standard-dose alteplase in the ENhanced Control of Hypertension and Thrombolysis strokE stuDy (ENCHANTED). Int J Stroke. 2015 Dec;10(8):1313-5. doi: 10.1111/ijs.12602. Epub 2015 Aug 18.

  PMID: 26283139 BACKGROUND

• Huang Y, Sharma VK, Robinson T, Lindley RI, Chen X, Kim JS, Lavados P, Olavarria V, Arima H, Fuentes S, Nguyen HT, Lee TH, Parsons MW, Levi C, Demchuk AM, Bath PM, Broderick JP, Donnan GA, Martins S, Pontes-Neto OM, Silva F, Pandian J, Ricci S, Stapf C, Woodward M, Wang J, Chalmers J, Anderson CS; ENCHANTED investigators. Rationale, design, and progress of the ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED) trial: An international multicenter 2 x 2 quasi-factorial randomized controlled trial of low- vs. standard-dose rt-PA and early intensive vs. guideline-recommended blood pressure lowering in patients with acute ischaemic stroke eligible for thrombolysis treatment. Int J Stroke. 2015 Jul;10(5):778-88. doi: 10.1111/ijs.12486. Epub 2015 Apr 2.

  PMID: 25832995 BACKGROUND

• Anderson CS, Woodward M, Arima H, Chen X, Lindley RI, Wang X, Chalmers J, Robinson TG. Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy. Int J Stroke. 2019 Jul;14(5):555-558. doi: 10.1177/1747493018806170. Epub 2018 Oct 9.

  PMID: 30299230 BACKGROUND

• Anderson CS, Robinson T, Lindley RI, Arima H, Lavados PM, Lee TH, Broderick JP, Chen X, Chen G, Sharma VK, Kim JS, Thang NH, Cao Y, Parsons MW, Levi C, Huang Y, Olavarria VV, Demchuk AM, Bath PM, Donnan GA, Martins S, Pontes-Neto OM, Silva F, Ricci S, Roffe C, Pandian J, Billot L, Woodward M, Li Q, Wang X, Wang J, Chalmers J; ENCHANTED Investigators and Coordinators. Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke. N Engl J Med. 2016 Jun 16;374(24):2313-23. doi: 10.1056/NEJMoa1515510. Epub 2016 May 10.

  PMID: 27161018 RESULT

• Anderson CS, Huang Y, Lindley RI, Chen X, Arima H, Chen G, Li Q, Billot L, Delcourt C, Bath PM, Broderick JP, Demchuk AM, Donnan GA, Durham AC, Lavados PM, Lee TH, Levi C, Martins SO, Olavarria VV, Pandian JD, Parsons MW, Pontes-Neto OM, Ricci S, Sato S, Sharma VK, Silva F, Song L, Thang NH, Wardlaw JM, Wang JG, Wang X, Woodward M, Chalmers J, Robinson TG; ENCHANTED Investigators and Coordinators. Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial. Lancet. 2019 Mar 2;393(10174):877-888. doi: 10.1016/S0140-6736(19)30038-8. Epub 2019 Feb 7.

  PMID: 30739745 RESULT

• Liu F, Ren X, Chen C, Ouyang M, Li Q, Wang X, Zhang G, Zhang L, Liu L, You S, Lindley RI, Robinson T, Sui Y, Li G, Anderson C, Song L; ENCHANTED Investigators. Early blood pressure lowering and cerebral oedema in thrombolysis-treated stroke: secondary analysis of the ENCHANTED trial. Stroke Vasc Neurol. 2025 Nov 4:svn-2025-004463. doi: 10.1136/svn-2025-004463. Online ahead of print.

  PMID: 41192975 DERIVED

• Zhang G, Chen C, Ren X, Zhao Y, Ouyang M, Billot L, Li Q, Wang X, Zhang L, Ong S, Liu L, You S, Lindley RI, Robinson TG, Li G, Chen X, Sui Y, Anderson CS, Song L; ENCHANTED Investigators. Effects of Intensive Blood Pressure Lowering on Brain Swelling in Thrombolyzed Acute Ischemic Stroke: The ENCHANTED Results. Stroke. 2025 Jun;56(6):1388-1395. doi: 10.1161/STROKEAHA.124.049938. Epub 2025 Apr 3.

  PMID: 40177745 DERIVED

• Wang Y, Maeda T, You S, Chen C, Liu L, Zhou Z, Robinson TG, Lindley RI, Delcourt C, Mair G, Wardlaw JM, Chalmers JP, Arima H, Huang Y, Kim JS, Lavados PM, Lee TH, Levi C, Parsons MW, Martins SC, Pandian JD, Pontes-Neto OM, Sharma VK, Nguyen TH, Wang J, Wu S, Liu M, Anderson CS, Chen X; ENCHANTED Investigators. Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results From the ENCHANTED Study. Neurology. 2024 Dec 10;103(11):e210020. doi: 10.1212/WNL.0000000000210020. Epub 2024 Nov 14.

  PMID: 39541551 DERIVED

• You S, Wang Y, Wang X, Maeda T, Ouyang M, Han Q, Li Q, Song L, Zhao Y, Chen C, Delcourt C, Ren X, Carcel C, Zhou Z, Cao Y, Liu CF, Zheng D, Arima H, Robinson TG, Chen X, Lindley RI, Chalmers J, Anderson CS. Twenty-Four-Hour Post-Thrombolysis NIHSS Score As the Strongest Prognostic Predictor After Acute Ischemic Stroke: ENCHANTED Study. J Am Heart Assoc. 2024 Sep 17;13(18):e036109. doi: 10.1161/JAHA.124.036109. Epub 2024 Sep 11.

  PMID: 39258531 DERIVED

• Wang X, You S, Zhou Z, Delcourt C, Wardlaw J, Mair G, Robinson T, Chen X, Yoshimura S, Torii-Yoshimura T, Carcel C, Malavera A, Anderson C, Lindley RI. Baseline brain imaging signs in patients with ischaemic stroke by the presence of atrial fibrillation: the ENCHANTED trial. J Neurol. 2023 May;270(5):2567-2575. doi: 10.1007/s00415-023-11580-x. Epub 2023 Mar 20.

  PMID: 36939933 DERIVED

• Chen C, Ouyang M, Ong S, Zhang L, Zhang G, Delcourt C, Mair G, Liu L, Billot L, Li Q, Chen X, Parsons M, Broderick JP, Demchuk AM, Bath PM, Donnan GA, Levi C, Chalmers J, Lindley RI, Martins SO, Pontes-Neto OM, Venturelli PM, Olavarria V, Lavados P, Robinson TG, Wardlaw JM, Li G, Wang X, Song L, Anderson CS. Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial. EClinicalMedicine. 2023 Feb 15;57:101849. doi: 10.1016/j.eclinm.2023.101849. eCollection 2023 Mar.

  PMID: 36820100 DERIVED

• Wang X, Minhas JS, Moullaali TJ, Di Tanna GL, Lindley RI, Chen X, Arima H, Chen G, Delcourt C, Bath PM, Broderick JP, Demchuk AM, Donnan GA, Durham AC, Lavados PM, Lee TH, Levi C, Martins SO, Olavarria VV, Pandian JD, Parsons MW, Pontes-Neto OM, Ricci S, Sato S, Sharma VK, Silva F, Thang NH, Wang JG, Woodward M, Chalmers J, Song L, Anderson CS, Robinson TG; ENCHANTED Investigators. Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis-Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study. Stroke. 2022 Mar;53(3):779-787. doi: 10.1161/STROKEAHA.121.034580. Epub 2021 Oct 27.

  PMID: 34702064 DERIVED

• Zhou Z, Xia C, Mair G, Delcourt C, Yoshimura S, Liu X, Chen Z, Malavera A, Carcel C, Chen X, Wang X, Al-Shahi Salman R, Robinson TG, Lindley RI, Chalmers J, Wardlaw JM, Parsons MW, Demchuk AM, Anderson CS. Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target. Int J Stroke. 2022 Jun;17(5):566-575. doi: 10.1177/17474930211025436. Epub 2021 Jun 24.

  PMID: 34096413 DERIVED

• Zhou Z, Delcourt C, Xia C, Yoshimura S, Carcel C, Torii-Yoshimura T, You S, Malavera A, Chen X, Hackett ML, Woodward M, Chalmers J, Xu J, Robinson TG, Parsons MW, Demchuk AM, Lindley RI, Mair G, Wardlaw JM, Anderson CS. Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke: The ENCHANTED Trial. Neurology. 2021 Mar 16;96(11):e1512-e1526. doi: 10.1212/WNL.0000000000011598. Epub 2021 Feb 3.

  PMID: 33536271 DERIVED

• Sun L, Song L, Yang J, Lindley RI, Robinson T, Lavados PM, Delcourt C, Arima H, Ovbiagele B, Chalmers J, Anderson CS, Wang X. Smoking influences outcome in patients who had thrombolysed ischaemic stroke: the ENCHANTED study. Stroke Vasc Neurol. 2021 Sep;6(3):395-401. doi: 10.1136/svn-2020-000493. Epub 2021 Feb 1.

  PMID: 33526633 DERIVED

• Zhou Z, Xia C, Carcel C, Yoshimura S, Wang X, Delcourt C, Malavera A, Chen X, Mair G, Woodward M, Chalmers J, Demchuk AM, Lindley RI, Robinson TG, Parsons MW, Wardlaw JM, Anderson CS. Intensive versus guideline-recommended blood pressure reduction in acute lacunar stroke with intravenous thrombolysis therapy: The ENCHANTED trial. Eur J Neurol. 2021 Mar;28(3):783-793. doi: 10.1111/ene.14598. Epub 2020 Dec 1.

  PMID: 33069172 DERIVED

• Minhas JS, Wang X, Lindley RI, Delcourt C, Song L, Woodward M, Lee TH, Broderick JP, Pontes-Neto OM, Kim JS, Ricci S, Lavados PM, Bath PM, Durham AC, Wang JG, Sharma VK, Demchuk AM, Martins SO, Chalmers J, Anderson CS, Robinson TG; ENCHANTED Investigators. Comparative effects of intensive-blood pressure versus standard-blood pressure-lowering treatment in patients with severe ischemic stroke in the ENCHANTED trial. J Hypertens. 2021 Feb 1;39(2):280-285. doi: 10.1097/HJH.0000000000002640.

  PMID: 33031175 DERIVED

• Wang X, Moullaali TJ, Li Q, Berge E, Robinson TG, Lindley R, Zheng D, Delcourt C, Arima H, Song L, Chen X, Yang J, Chalmers J, Anderson CS, Sandset EC. Utility-Weighted Modified Rankin Scale Scores for the Assessment of Stroke Outcome: Pooled Analysis of 20 000+ Patients. Stroke. 2020 Aug;51(8):2411-2417. doi: 10.1161/STROKEAHA.119.028523. Epub 2020 Jul 9.

  PMID: 32640944 DERIVED

• Zhou Z, Yoshimura S, Delcourt C, Lindley RI, You S, Malavera A, Torii-Yoshimura T, Carcel C, Wang X, Chen X, Parsons MW, Demchuk AM, Wardlaw JM, Mair G, Robinson TG, Chalmers J, Xu J, Anderson CS. Thrombolysis Outcomes in Acute Ischemic Stroke by Fluid-Attenuated Inversion Recovery Hyperintense Arteries. Stroke. 2020 Jul;51(7):2240-2243. doi: 10.1161/STROKEAHA.119.028550. Epub 2020 Jun 17.

  PMID: 32568636 DERIVED

• Chen X, Li J, Anderson CS, Lindley RI, Hackett ML, Robinson T, Lavados PM, Wang X, Arima H, Chalmers J, Delcourt C; ENCHANTED Investigators. Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm. Int J Stroke. 2021 Feb;16(2):222-228. doi: 10.1177/1747493019897858. Epub 2020 Jan 22.

  PMID: 31969072 DERIVED

• Chen X, Wang X, Delcourt C, Li J, Arima H, Hackett ML, Robinson T, Lavados PM, Lindley RI, Chalmers J, Anderson CS; ENCHANTED Investigators. Ethnicity and Other Determinants of Quality of Functional Outcome in Acute Ischemic Stroke: The ENCHANTED Trial. Stroke. 2020 Feb;51(2):588-593. doi: 10.1161/STROKEAHA.119.027639. Epub 2019 Dec 11.

  PMID: 31822251 DERIVED

• Wang X, Song L, Yang J, Sun L, Moullaali TJ, Sandset EC, Delcourt C, Lindley RI, Robinson TG, Minhas JS, Arima H, Chalmers J, Kim JS, Sharma V, Wang JG, Pontes-Neto O, Lavados PM, Olavarria VV, Lee TH, Levi C, Martins SO, Thang NH, Anderson CS; on behalf of the ENCHANTED Investigators. Interaction of Blood Pressure Lowering and Alteplase Dose in Acute Ischemic Stroke: Results of the Enhanced Control of Hypertension and Thrombolysis Stroke Study. Cerebrovasc Dis. 2019;48(3-6):207-216. doi: 10.1159/000504745. Epub 2019 Dec 6.

  PMID: 31812956 DERIVED

• Robinson TG, Bray BD, Paley L, Sprigg N, Wang X, Arima H, Bath PM, Broderick JP, Durham AC, Kim JS, Lavados PM, Lee TH, Martins S, Nguyen TH, Pandian JD, Parsons MW, Pontes-Neto OM, Ricci S, Sharma VK, Wang J, Woodward M, Rudd AG, Chalmers J, S Anderson C; ENCHANTED Investigators and the SSNAP Collaboration. Applicability of ENCHANTED trial results to current acute ischemic stroke patients eligible for intravenous thrombolysis in England and Wales: Comparison with the Sentinel Stroke National Audit Programme registry. Int J Stroke. 2019 Oct;14(7):678-685. doi: 10.1177/1747493019841246. Epub 2019 Apr 8.

  PMID: 30961463 DERIVED

• Robinson TG, Wang X, Durham AC, Ford GA, Liao J, Littlewood S, Roffe C, White P, Chalmers J, Anderson CS; ENCHANTED Investigators. The National Institute for Health Research Hyperacute Stroke Research Centres and the ENCHANTED trial: the impact of enhanced research infrastructure on trial metrics and patient outcomes. Health Res Policy Syst. 2019 Feb 13;17(1):19. doi: 10.1186/s12961-019-0417-2.

  PMID: 30760277 DERIVED

• Yoshimura S, Lindley RI, Carcel C, Sato S, Delcourt C, Wang X, Chalmers J, Anderson CS; ENCHANTED Investigators. NIHSS cut point for predicting outcome in supra- vs infratentorial acute ischemic stroke. Neurology. 2018 Oct 30;91(18):e1695-e1701. doi: 10.1212/WNL.0000000000006437. Epub 2018 Sep 28.

  PMID: 30266885 DERIVED

• Nagel S, Wang X, Carcel C, Robinson T, Lindley RI, Chalmers J, Anderson CS; ENCHANTED Investigators. Clinical Utility of Electronic Alberta Stroke Program Early Computed Tomography Score Software in the ENCHANTED Trial Database. Stroke. 2018 Jun;49(6):1407-1411. doi: 10.1161/STROKEAHA.117.019863. Epub 2018 May 18.

  PMID: 29777016 DERIVED

• Chen G, Wang X, Robinson TG, Pikkemaat M, Lindley RI, Zhou S, Ping L, Liu W, Liu L, Chalmers J, Anderson CS; ENCHANTED Investigators. Comparative effects of low-dose versus standard-dose alteplase in ischemic patients with prior stroke and/or diabetes mellitus: The ENCHANTED trial. J Neurol Sci. 2018 Apr 15;387:1-5. doi: 10.1016/j.jns.2018.01.014. Epub 2018 Jan 11.

  PMID: 29571842 DERIVED

• Kim JS, Kim YJ, Lee KB, Cha JK, Park JM, Hwang Y, Kim EG, Rha JH, Koo J, Kim J, Kim YJ, Seo WK, Kim DE, Robinson TG, Lindley RI, Wang X, Chalmers J, Anderson CS. Low- versus Standard-Dose Intravenous Alteplase in the Context of Bridging Therapy for Acute Ischemic Stroke: A Korean ENCHANTED Study. J Stroke. 2018 Jan;20(1):131-139. doi: 10.5853/jos.2017.01578. Epub 2018 Jan 31.

  PMID: 29402064 DERIVED

• Xu Y, Hackett ML, Chalmers J, Lindley RI, Wang X, Li Q, Robinson T, Arima H, Lavados PM, Anderson CS; ENCHANTED Study Group. Frequency, determinants, and effects of early seizures after thrombolysis for acute ischemic stroke: The ENCHANTED trial. Neurol Clin Pract. 2017 Aug;7(4):324-332. doi: 10.1212/CPJ.0000000000000384.

  PMID: 29185557 DERIVED

• Wang X, Robinson TG, Lee TH, Li Q, Arima H, Bath PM, Billot L, Broderick J, Demchuk AM, Donnan G, Kim JS, Lavados P, Lindley RI, Martins SO, Olavarria VV, Pandian JD, Parsons MW, Pontes-Neto OM, Ricci S, Sharma VK, Thang NH, Wang JG, Woodward M, Anderson CS, Chalmers J; Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) Investigators. Low-Dose vs Standard-Dose Alteplase for Patients With Acute Ischemic Stroke: Secondary Analysis of the ENCHANTED Randomized Clinical Trial. JAMA Neurol. 2017 Nov 1;74(11):1328-1335. doi: 10.1001/jamaneurol.2017.2286.

  PMID: 28973174 DERIVED

• Carr SJ, Wang X, Olavarria VV, Lavados PM, Rodriguez JA, Kim JS, Lee TH, Lindley RI, Pontes-Neto OM, Ricci S, Sato S, Sharma VK, Woodward M, Chalmers J, Anderson CS, Robinson TG; ENCHANTED Investigators. Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis. Stroke. 2017 Sep;48(9):2605-2609. doi: 10.1161/STROKEAHA.117.017808. Epub 2017 Jul 24.

  PMID: 28739832 DERIVED

• Robinson TG, Wang X, Arima H, Bath PM, Billot L, Broderick JP, Demchuk AM, Donnan GA, Kim JS, Lavados PM, Lee TH, Lindley RI, Martins SCO, Olavarria VV, Pandian JD, Parsons MW, Pontes-Neto OM, Ricci S, Sato S, Sharma VK, Nguyen TH, Wang JG, Woodward M, Chalmers J, Anderson CS; ENCHANTED Investigators. Low- Versus Standard-Dose Alteplase in Patients on Prior Antiplatelet Therapy: The ENCHANTED Trial (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Stroke. 2017 Jul;48(7):1877-1883. doi: 10.1161/STROKEAHA.116.016274. Epub 2017 Jun 15.

  PMID: 28619989 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Hypertension

Interventions

Tissue Plasminogen Activator; Labetalol; Metoprolol; Hydralazine; Nitroglycerin; Phentolamine; Nicardipine; urapidil; esmolol; Clonidine; Enalaprilat

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Salicylamides; Amides; Amines; Phenoxypropanolamines; Propanolamines; Propanols; Phthalazines; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitro Compounds; Imidazoles; Azoles; Dihydropyridines; Pyridines; Imidazolines; Enalapril; Dipeptides; Oligopeptides; Peptides

Study Officials

• Craig S Anderson, MD

  The George Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2011
• First Posted: August 24, 2011
• Study Start: March 1, 2012
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: October 13, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: available
• Access Criteria: approved protocol, ethics committee and data sharing agreement

Locations

AU (1)