Ischemic StrokePhase 3ENCHANTEDNCT01422616

Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)

A Phase 3 study testing Low-dose rtPA, Standard-dose rtPA and Intensive blood pressure (BP) lowering in people with Ischemic Stroke and High Blood Pressure, run by The George Institute at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Ischemic Stroke, High Blood Pressure
What is being tested?: Low-dose rtPA, Standard-dose rtPA and Intensive blood pressure (BP) lowering
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4,587 participants
Where: 1 siteAustralia
Study dates: Mar 2012to Aug 2018
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.):

Show all 12Show fewer

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

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

Royal Prince Alfred Hospital
Sydney, New South Wales, 2050

Other trials in Australia

About this study

Official title: An International Randomised Controlled Trial to Establish the Effects of Low-dose rtPA and the Effects of Early Intensive Blood Pressure Lowering in Patients With Acute Ischaemic Stroke

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.

Read the detailed description

This study is an international, multicentre, prospective, fixed-time point (optional) randomisation for two arms ([A] 'dose of rtPA' and [B] 'level of BP control'), open-label, blinded endpoint (PROBE) controlled trial that involved 4587 patients (3310 for rtPA arm {recruitment completed in August 2015} and 2227 for BP arm {recruitment completed in April 2018} with 939 overlap) with acute ischaemic stroke recruited from over 100+ Clinical Centres from Australia, Asia, Europe and South America.

Conditions: Ischemic Stroke, High Blood Pressure
Being tested: Low-dose rtPA, Standard-dose rtPA, Intensive blood pressure (BP) lowering, BP management policies
Keywords: Ischemic stroke, High blood pressure, Thrombolysis, Antihypertensive drugs, Disability, Clinical trial
Medical subject headings: Ischemic Stroke, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Low-dose rtPADrug
Also called Actilyse
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).
Standard-dose rtPADrug
Also called Actilyse
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.
Intensive blood pressure (BP) loweringOther
Also called Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol Trinitrate
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.
BP management policiesOther
Also called Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol Trinitrate
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.

Study groups in NCT01422616
Study group	Role	What they receive
Low-dose rtPA (Recruitment completed in August 2015)	Experimental	low-dose 0.6 mg/kg (maximum of 60 mg) i.v. rtPA Receives: 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 Receives: 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. Receives: 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. Receives: Other: BP management policies

What is being measured

The primary outcome is the main question the study is designed to answer.

Combined death and disability
Unadjusted modified Rankin Scale [mRS] score 2-6
Measured: 90 days

Secondary outcomes (16)

Symptomatic intracerebral hemorrhage
Brain imaging (or necropsy) confirmed ICH with deterioration in NIH Stroke Scale (NIHSS) score or death, as defined by the SITS-MOST criteria
Measured: 36 hours
Symptomatic intracerebral hemorrhage
Brain imaging (or necropsy) confirmed ICH with deterioration in NIH Stroke Scale (NIHSS) score or death, as defined by the NINDS trial criteria
Measured: 36 hours
Death or disability by the alternative, ordinal shift analysis
Unadjusted death or functional outcome by the alternative ordinal shift analysis of scores on the modified Rankin Scale [mRS]
Measured: 90 days
Death
Death and 7 and 90 days
Measured: at 7 and 90 days
Disability
mRS score 2-5
Measured: 90 days
Neurological deterioration
deterioration in NIHSS score
Measured: 72 hours
Health-related quality of life
Health-related quality of life by the EuroQoL
Measured: 90 days
Admission to residential care
Measured: 90 days
Health service use
Health service use for calculation of resources and costs
Measured: 90 days
Symptomatic intracerebral hemorrhage (ICH)
By various other centrally adjudicated criteria, including ECASS2, ECASS3, IST-3 criteria, and fatal ICH within 7 days
Measured: within 7 days
Any intracerebral hemorrhage (ICH)
Centrally adjudicated review of brain imaging for any evidence of ICH
Measured: any time during 90 days
Death or disability in as treated per-protocol population
Adjusted death or functional outcome by the binary and alternative ordinal shift analysis of scores on the modified Rankin Scale [mRS]
Measured: 90 days
Death or disability in as treated per-protocol population
Adjusted analysis of the modified Rankin Scale [mRS] score 2-6
Measured: 90 days
Death or neurological deterioration
Death or neurological deterioration (defined by 4 points or more increase in NIHSS score from baseline)
Measured: 72 hours
Length of initial acute hospital stay
Length of hospital stay in days
Measured: within 90 days
Recurrent acute myocardial infarction and ischemic stroke
Recurrent acute myocardial infarction and ischemic stroke
Measured: within 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2012Aug 2018

First posted24 Aug 2011 (estimated)
Study startMar 2012
Primary completionAug 2018
Study completionAug 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (34)Papers the sponsor has linked to this study.
Other trials for Ischemic StrokeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 4,587 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01422616
Sponsor's protocol ID: X11-0123
Acronym: ENCHANTED
Status last verified: Oct 2021
First submitted: 23 Aug 2011
Last updated: 13 Oct 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Data sharing upon approval through formal application to the Research Office of The George Institute for Global Health, Australia

Publications

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.
PubMed 26283139
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.
PubMed 25832995
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.
PubMed 30299230
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.
PubMed 27161018
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.
PubMed 30739745
Ge Y, Gao Y, Chen X, Liu C, Lindley RI, Arima H, Chen G, Delcourt C, Bath PM, Broderick JP, Demchuk AM, Donnan GA, Lavados PM, Lee TH, Martins SO, Pandian JD, Parsons MW, Pontes-Neto OM, Nguyen TH, Chalmers J, Song L, Robinson TG, Wang X, Anderson CS; ENCHANTED Investigators. Body Weight in Relation to the Effectiveness of Intravenous Alteplase in Acute Ischemic Stroke: The ENCHANTED Trial. Stroke. 2026 Aug 26. doi: 10.1161/STROKEAHA.125.053569. Online ahead of print.
PubMed 42644244
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. 2026 Jun 29;11(3):349-357. doi: 10.1136/svn-2025-004463.
PubMed 41192975
Zhou Z, Ge Y, Yoshimura S, Torii-Yoshimura T, Sakamoto Y, Liu X, Carcel C, Chen X, Liu L, Parsons M, Mair G, Lindley RI, Wardlaw J, Anderson CS, Delcourt C. Intravenous thrombolysis in patients with acute ischemic stroke and cerebral microbleeds: Results from the ENCHANTED trial. Int J Stroke. 2026 Jun;21(5):657-666. doi: 10.1177/17474930251392751. Epub 2025 Oct 23.
PubMed 41131698
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.
PubMed 40177745
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.
PubMed 39541551
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.
PubMed 39258531
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.
PubMed 36939933
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.
PubMed 36820100
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.
PubMed 34702064
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.
PubMed 34096413

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
Active, not recruiting
Improving Visual Field Deficits With Noninvasive Brain Stimulation
Visual Field Defect, Peripheral, Stroke
Recruiting
Biomarkers of Paired VNS
Stroke, Ischemic

All Ischemic Stroke trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An International Randomised Controlled Trial to Establish the Effects of Low-dose rtPA and the Effects of Early Intensive Blood Pressure Lowering in Patients With Acute Ischaemic Stroke
ClinicalTrials.gov ID: NCT01422616
Acronym / sponsor ID: ENCHANTED / X11-0123
Conditions: Ischemic Stroke, High Blood Pressure
Keywords: Ischemic stroke, High blood pressure, Thrombolysis, Antihypertensive drugs, Disability, Clinical trial
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 4,587 participants (actual)
Lead sponsor: The George InstituteUniversity, hospital or other
Collaborators: National Health and Medical Research Council, Australia, The Stroke Association, United Kingdom, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Takeda
Study start: Mar 2012 (actual)
Primary completion: Aug 2018 (actual)
Study completion: Aug 2018 (actual)
First posted: 24 Aug 2011 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Single blind (outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Low-dose rtPA (Recruitment completed in August 2015)	Experimental	Drug: Low-dose rtPAlow-dose 0.6 mg/kg (maximum of 60 mg) i.v. rtPA
Standard-dose rtPA (Recruitment completed in August 2015)	Active comparator	Drug: Standard-dose rtPAstandard-dose 0.9 mg/kg (maximum of 90 mg) i.v. rtPA
Early intensive BP lowering	Experimental	Other: Intensive blood pressure (BP) loweringThe 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.
Control / guideline-based BP management	Active comparator	Other: BP management policiesThe 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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)

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Low-dose rtPAAlso: ActilysePatients 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).	Drug	Low-dose rtPA (Recruitment completed in August 2015)
Standard-dose rtPAAlso: ActilysePatients 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.	Drug	Standard-dose rtPA (Recruitment completed in August 2015)
Intensive blood pressure (BP) loweringAlso: Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol TrinitrateIntensive 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.	Other	Early intensive BP lowering
BP management policiesAlso: Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol TrinitratePatients 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.	Other	Control / guideline-based BP management

Primary outcome

Combined death and disability
Time frame: 90 days
Unadjusted modified Rankin Scale [mRS] score 2-6

16 secondary outcomes

Symptomatic intracerebral hemorrhage
Time frame: 36 hours
Symptomatic intracerebral hemorrhage
Time frame: 36 hours
Death or disability by the alternative, ordinal shift analysis
Time frame: 90 days
Death
Time frame: at 7 and 90 days
Disability
Time frame: 90 days
Neurological deterioration
Time frame: 72 hours
Health-related quality of life
Time frame: 90 days
Admission to residential care
Time frame: 90 days
Health service use
Time frame: 90 days
Symptomatic intracerebral hemorrhage (ICH)
Time frame: within 7 days
Any intracerebral hemorrhage (ICH)
Time frame: any time during 90 days
Death or disability in as treated per-protocol population
Time frame: 90 days
Death or disability in as treated per-protocol population
Time frame: 90 days
Death or neurological deterioration
Time frame: 72 hours
Length of initial acute hospital stay
Time frame: within 90 days
Recurrent acute myocardial infarction and ischemic stroke
Time frame: within 90 days

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
Background: PubMed 26283139Anderson 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.
Background: PubMed 25832995Huang 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.
Background: PubMed 30299230Anderson 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.
Results publication: PubMed 27161018Anderson 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.
Results publication: PubMed 30739745Anderson 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.
Derived from this study: PubMed 42644244Ge Y, Gao Y, Chen X, Liu C, Lindley RI, Arima H, Chen G, Delcourt C, Bath PM, Broderick JP, Demchuk AM, Donnan GA, Lavados PM, Lee TH, Martins SO, Pandian JD, Parsons MW, Pontes-Neto OM, Nguyen TH, Chalmers J, Song L, Robinson TG, Wang X, Anderson CS; ENCHANTED Investigators. Body Weight in Relation to the Effectiveness of Intravenous Alteplase in Acute Ischemic Stroke: The ENCHANTED Trial. Stroke. 2026 Aug 26. doi: 10.1161/STROKEAHA.125.053569. Online ahead of print.
Derived from this study: PubMed 41192975Liu 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. 2026 Jun 29;11(3):349-357. doi: 10.1136/svn-2025-004463.
Derived from this study: PubMed 41131698Zhou Z, Ge Y, Yoshimura S, Torii-Yoshimura T, Sakamoto Y, Liu X, Carcel C, Chen X, Liu L, Parsons M, Mair G, Lindley RI, Wardlaw J, Anderson CS, Delcourt C. Intravenous thrombolysis in patients with acute ischemic stroke and cerebral microbleeds: Results from the ENCHANTED trial. Int J Stroke. 2026 Jun;21(5):657-666. doi: 10.1177/17474930251392751. Epub 2025 Oct 23.
Derived from this study: PubMed 40177745Zhang 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.
Derived from this study: PubMed 39541551Wang 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.
Derived from this study: PubMed 39258531You 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.
Derived from this study: PubMed 36939933Wang 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.
Individual participant dataSharing planned: Yes. Data sharing upon approval through formal application to the Research Office of The George Institute for Global Health, Australia

Related trials for Ischemic Stroke

Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
Active, not recruiting
Improving Visual Field Deficits With Noninvasive Brain Stimulation
Visual Field Defect, Peripheral, Stroke
Recruiting
Biomarkers of Paired VNS
Stroke, Ischemic

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Craig S Anderson, MD principal investigator

The George Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Combined death and disability (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01422616, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2021.