Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Low-dose rtPA · 1 trial · 2 indications
Unadjusted modified Rankin Scale \[mRS\] score 2-6
| Arm | Type | Description |
|---|---|---|
| Low-dose rtPA (Recruitment completed in August 2015) | EXPERIMENTAL | low-dose 0.6 mg/kg (maximum of 60 mg) i.v. rtPA |
| Standard-dose rtPA (Recruitment completed in August 2015) | ACTIVE_COMPARATOR | standard-dose 0.9 mg/kg (maximum of 90 mg) i.v. 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
Inclusion Criteria: * 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, a...
Low-dose rtPA is used for the treatment of ischemic stroke. It is a small molecule being investigated as a thrombolytic agent to break up blood clots in patients with acute ischemic stroke. The drug is currently in Phase 3 clinical development and is not yet approved for this indication.
Low-dose rtPA targets the fibrinolytic system by converting plasminogen to plasmin, which degrades fibrin clots. This mechanism helps restore blood flow in ischemic stroke patients. The drug is a small molecule designed to achieve this effect at a lower dose than standard therapy.
Low-dose rtPA is being developed by Takeda Pharmaceutical Company Limited, a global biopharmaceutical company. Takeda is listed on the stock exchange under the ticker symbol TAK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in ischemic stroke.
Low-dose rtPA is in Phase 3 clinical development for ischemic stroke. It is an investigational drug and has not received FDA approval. The Phase 3 trial, known as ENCHANTED, has been completed, and the drug is not yet available for commercial use.
Low-dose rtPA has been studied in one completed Phase 3 trial, NCT01422616, titled 'Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)'. This trial enrolled 4,587 patients with ischemic stroke and high blood pressure in Australia. The study was active-controlled and randomized, with no active trials currently ongoing.
Low-dose rtPA is a lower-dose formulation of recombinant tissue plasminogen activator (rtPA), which is a standard thrombolytic therapy for ischemic stroke. The ENCHANTED trial compared low-dose rtPA to standard-dose rtPA to assess whether a lower dose could reduce bleeding risk while maintaining efficacy.