INTERACT4 Trial: Prehospital Blood-Pressure Reduction Before Stroke Type Is Known
In patients with suspected acute stroke and hypertension managed in the ambulance, does initiating intensive IV blood-pressure reduction before imaging diagnosis improve functional outcome at 90 days?
INTERACT4 Investigators (NEJM 2024) · doi:10.1056/NEJMoa2314741 · 2404 patients
Population
Included
- Age 18 or older
- FAST score ≥2 with arm motor deficit
- Systolic BP ≥150 mm Hg
- Treatment initiation within 2 hours of onset or last known well
- Adult patients 18 years of age or older
- Presumed acute stroke, defined as a Face-Arm-Speech-Time (FAST) score of 2 or higher (range 0 to 4, higher scores indicating more symptoms) that included an arm motor deficit
- Elevated systolic blood pressure of 150 mm Hg or higher
- Ability to start treatment within 2 hours after symptom onset or after the time the patient was last known to be well
- Assessed by ambulance staff who were doctors employed by the participating ambulance services
Excluded
- Coma or severe comorbidity
- Epilepsy, recent head injury, or hypoglycemia
- Inability to confirm eligibility or initiate treatment within 2 hours
- In a coma
- Severe coexisting disease
- Epilepsy
- Recent head injury
- Hypoglycemia
Source: INTERACT4 Investigators (Li G et al.), N Engl J Med 2024;390:1862–1872· Retrieved 2026-06-09
Primary Outcome — mRS Distribution at 90 Days
Undifferentiated stroke (all patients)
Study Arms
- Agent
- Urapidil (an intravenous alpha-1 adrenoceptor antagonist with 5-HT1A agonist activity, widely used in China)
- Dose
- Intravenous bolus of 25 mg over 1 minute, repeated once after 5 minutes if blood pressure remained elevated
- Route
- IV
- Frequency
- Bolus, repeatable once at 5 minutes; further treatment with urapidil or another agent (bolus, infusion, or oral) continued in the emergency department, stroke unit, or monitored facility
- Duration
- Started in the ambulance and maintained until hospital arrival
- Co-interventions
- Patients kept horizontal with blood pressure monitored every 5 minutes during transport. In-hospital blood-pressure management and other care per established local guidelines (China: target systolic <140 mm Hg for hemorrhagic stroke, 140 to 160 mm Hg for ischemic stroke).
Goal systolic blood pressure 130 to 140 mm Hg within 30 minutes, maintained until arrival at the hospital. A systolic blood pressure of 130 mm Hg was the threshold for cessation of treatment. Source: Li NEJM 2024 p.1864.
- Agent
- Usual prehospital care (commencement of blood-pressure management on arrival at the hospital)
- Route
- IV (in ambulance only at high thresholds)
- Co-interventions
- In the ambulance, treatment to lower blood pressure used only for systolic blood pressure of 220 mm Hg or higher or diastolic blood pressure of 110 mm Hg or higher. Both groups received in-hospital blood-pressure management and other care per established local guidelines.
Control arm represents commencement of blood-pressure management on arrival at the hospital rather than in the ambulance. Source: Li NEJM 2024 p.1864.
Trial Design
Type
- Randomized, open-label, blinded-endpoint trial
- Ambulance-based blood-pressure lowering before imaging diagnosis
- Undifferentiated stroke population with SBP >=150 mm Hg within 2 hours
Timeline
China; prehospital acute stroke network
N
2404
Enrollment
Randomized Mar 2020 to Aug 2023 at 51 hospitals in China. Open-label, blinded endpoint (PROBE design).
Bedside Pearl
Type-blind prehospital BP lowering is a zero-sum strategy: you help your hemorrhagic strokes and hurt your ischemic strokes in roughly equal measure. The overall null result is not reassurance that early BP reduction is safe across the board. Without imaging to confirm stroke type, aggressive prehospital BP reduction is not routinely indicated.
See also