RIGHT-2
PubMed • PDF
Clinical Question
In patients with presumed stroke within 4 hours of onset, does paramedic-delivered transdermal glyceryl trinitrate (GTN) versus sham reduce death and dependency (assessed using the modified Rankin scale) at 90 days?
Bottom Line
The trial recruited 1149 patients from 8 Ambulance Services in England & Wales confirming that it is feasible to perform a multicentre paramedic-led ambulance-based trial in patients with presumed stroke in the UK. The effect of GTN has yet to be analysed since the trial is in follow-up and the database has yet to be locked and analysed.
Major Points
Pilot data from a small ambulance-based trial found that GTN lowered blood pressure and appeared to reduce death and dependency. Similar findings were found in patients randomised within 6 hours of stroke onset in the ENOS trial. The RIGHT-2 trial was designed to test these findings.
Guidelines
No guidelines have incorporated findings to date – trial in follow-up.
Design
- UK-based multicentre parallel-group prospective randomised sham-controlled blinded-endpoint trial
- N=1,149
- Setting: 8 Ambulance Services, 54 hospitals in the UK (England & Wales)
- Enrolment: 22 October 2015 to 23 May 2018
- Mean follow-up: 90 days
- Analysis: Hierarchical – modified intention-to-treat in target population (stroke and TIA); if positive, ITT in all patients
- Primary outcome: Death and dependency assessed using 7-level modified Rankin scale (mRS)
Population
Inclusion Criteria
- Emergency ‘999’ call
- Presumed stroke
- Randomisation within 4 hours of symptom onset
- Face/Arm/Speech Time (FAST) score = 2 or 3
- Systolic blood pressure >120 mmHg
- Written consent by patient with capacity, or proxy consent from relative, friend or paramedic
- Paramedic from participating Ambulance Service and trained in trial procedures
- Paramedic taking patient to participating Hospital with acute stroke service
Exclusion Criteria
- Patient from a Nursing Home
- Reduced consciousness, Glasgow Coma Scale <8
- Hypoglycaemia
- Witnessed seizure
Baseline Characteristics
- Not available – trial in follow-up
Interventions
- Randomised to glyceryl trinitrate (GTN, nitroglycerin) or sham
- GTN group received 5 mg unmarked patch immediately and then daily for 3 days
- Sham group received similar-looking unmarked Duoderm dressing immediately and then daily for 3 days
Outcomes
Feasible to recruit 1149 patients from 8 UK Ambulance Services over 31 months Comparisons are GTN vs. sham: awaited for completion of follow-up.
Primary Outcomes
- Hierarchical analysis using ordinal shift:
- 1. In stroke/TIA (modified ITT), not available – trial in follow-up
- 2. In all (ITT), not available – trial in follow-up
Secondary Outcomes
- Not available – trial in follow-up
Subgroup Analysis
- Not available – trial in follow-up
Adverse Events
- Not available – trial in follow-up
Criticisms
- High stroke mimic rate reflects problems of paramedics rapidly identifying stroke at the stroke scene
Funding
- British Heart Foundation
- Conflict of interest: Author is Chief Investigator and grant holder
Further Reading
- Appleton JP et al. Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: Rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053). Int J Stroke 2017. :1747493017724627.
- Scutt P, Appleton JP, Dixon M, et al. Statistical analysis plan for the ‘Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2). European Stroke Journal 2018