INTERACT4
(2024)Objective
To assess whether prehospital, intensive blood pressure reduction in suspected acute stroke improves 90-day functional outcomes compared to usual care.
Study Summary
Intervention
IV urapidil initiated in ambulance to target SBP 130–140 mm Hg vs. usual care (hospital-based BP management) for suspected stroke within 2 hours of symptom onset.
Inclusion Criteria
Age ≥18, FAST score ≥2 (with arm weakness), SBP ≥150 mm Hg, and ≤2 hours from symptom onset; excluded if coma, severe coexisting disease, epilepsy, recent head injury, or hypoglycemia.
Study Design
Arms: Prehospital BP Reduction vs. Usual BP Management
Patients per Arm: Intervention: 1205, Usual Care: 1199
Outcome
Bottom Line
Prehospital intensive BP reduction did not improve overall functional outcomes in undifferentiated stroke (common OR 1.00; 95% CI 0.87-1.15). However, effects diverged by stroke type: worse in ischemic stroke (common OR 1.30; 1.06-1.60) and better in hemorrhagic stroke (common OR 0.75; 0.60-0.92). Does not support universal ambulance-based BP-lowering for undifferentiated stroke.
Major Points
- Net null in undifferentiated stroke: common OR 1.00 (95% CI 0.87-1.15) for 90-day mRS shift.
- Divergent by stroke type: ischemic common OR 1.30 (1.06-1.60, HARM); hemorrhagic common OR 0.75 (0.60-0.92, BENEFIT).
- SBP at hospital arrival: 159 vs 170 mmHg — estimated between-group difference −15 mmHg in the ambulance and −4 mmHg in the hospital.
- 46.5% hemorrhagic, 53.5% ischemic among confirmed strokes — higher hemorrhagic proportion than Western populations.
- Mortality identical: 22.5% vs 22.6%. SAEs similar: 27.5% vs 28.7%.
- Urapidil (α-blocker) used in 98.2% (1172) of all patients across both groups who received any BP-lowering treatment — not widely available outside China.
- 89.5% of intervention group received ambulance BP treatment vs 9.7% in usual care.
- Supports prehospital stroke imaging (mobile CT) to guide individualized BP management.
- China-only, physician-staffed ambulances (99% Han Chinese). Limits Western generalizability.
- Consistent with RIGHT-2 and MR ASAP: prehospital BP reduction in undifferentiated stroke is not beneficial overall.
Study Design
- Study Type
- Randomized controlled trial (open-label, PROBE design)
- Randomization
- Yes
- Blinding
- Open-label; blinded 90-day outcome assessment. 1:1 with minimization algorithm stratified by region, age (≥65/<65), FAST score (≥3/2).
- Sample Size
- 2404
- Follow-up
- 90 days
- Centers
- 51
- Countries
- China
Primary Outcome
Definition: Distribution of mRS scores at 90 days (ordinal shift analysis)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| mRS 0-6 distribution (see details) | mRS 0-6 distribution (see details) | - (0.87-1.15) | NS |
Limitations & Criticisms
- Open-label — ambulance staff not blinded.
- China-only (99% Han Chinese); urapidil not available outside China.
- Divergent effects by stroke type but enrolled undifferentiated — net null is mixture of harm+benefit.
- Ischemic stroke common OR 1.30 concerning, especially for LVO where BP reduction may compromise penumbra.
- COVID-19 pandemic disruption during enrollment.
- Physician-staffed ambulances — not generalizable to paramedic systems.
- No adjustment for multiple comparisons in subgroup analyses.
- BP difference narrowed to −4 mmHg in the hospital — very brief treatment window.
- Partial industry sponsorship (Takeda, urapidil manufacturer).
Citation
N Engl J Med 2024;390:1862-72.