MR ASAP Trial: Prehospital Glyceryl Trinitrate Within 3 Hours of Presumed Stroke
In ambulance-treated patients with presumed stroke within 3 hours of onset, does prehospital transdermal glyceryl trinitrate improve 90-day functional outcome compared with standard care?
van den Berg SA, et al. (Lancet Neurol 2022) · doi:10.1016/S1474-4422(22)00333-7 · 325 patients
Population
Included
- Age 18 or older
- Presumed stroke with FAST score 2 or higher
- Onset or last known well within 3 hours
- Systolic blood pressure 140 mm Hg or higher
- Adult patients (aged 18 years or older)
- Probable diagnosis of acute stroke, as assessed by a paramedic in the prehospital setting
- Face-arm-speech-time (FAST) test score of 2 or 3
- Systolic blood pressure of at least 140 mm Hg
- Treatment could be started within 3 hours of symptom onset
Excluded
- Hypotension (systolic BP below 140 mm Hg)
- Nitrate use within 12 hours
- Known intracranial hemorrhage
- Severe comorbidity or reduced life expectancy
- Considerable pre-stroke dependency in activities of daily living, defined as staying in a chronic nursing home or rehabilitation centre
- A substantially reduced consciousness level (Glasgow Coma Scale below 8)
- A known contraindication or hypersensitivity to glyceryl trinitrate
Source: van den Berg SA et al., Lancet Neurol 2022;21(11):971–981· Retrieved 2026-06-09
Primary Outcome — mRS Distribution at 90 Days
Total population (presumed stroke within 3 hours)
Study Arms
- Agent
- Glyceryl trinitrate (nitroglycerin) transdermal patch (Deponit-T5; Merus Labs)
- Dose
- 5 mg/day
- Route
- Transdermal patch (shoulder, back, or chest)
- Frequency
- One patch
- Duration
- 24 hours (range 22 to 26 hours)
- Co-interventions
- Standard prehospital and in-hospital stroke care
Patch applied immediately after randomisation in the prehospital setting by the attending paramedic and continued during hospital admission for 24 hours. Open-label treatment with blinded endpoint assessment.
- Agent
- Standard prehospital and in-hospital stroke care
- Co-interventions
- No glyceryl trinitrate; admission to the acute stroke unit once a diagnosis of stroke was made
No prehospital nitrate administered. Otherwise identical pathway, including in-hospital thrombolysis and endovascular therapy as indicated.
Trial Design
Type
- Phase 3, randomized, open-label, blinded-endpoint trial
- Ambulance-based glyceryl trinitrate vs standard care
- Deferred-consent prehospital stroke trial
Timeline
Netherlands; April 2018 to February 2021
N
325
Enrollment
Randomized April 2018 to February 2021 in the Netherlands. Phase 3, ambulance-based, open-label, blinded-endpoint trial. Stopped after 380 of planned 1200 randomizations due to a safety signal in ICH patients.
Bedside Pearl
MR ASAP and RIGHT-2 together make the strongest case against prehospital GTN for undifferentiated stroke: no functional benefit in either trial, and an early harm signal in ICH patients treated before imaging. Early 7-day mortality was numerically higher with GTN in the ICH subgroup. Do not administer prehospital nitrates for presumed stroke before CT excludes hemorrhage.
See also