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Appleton JP, Scutt P, Dixon M, Howard H, Haywood L, Havard D, Hepburn T, England T, Sprigg N, Woodhouse LJ, Wardlaw JM, Montgomery AA, Pocock S, Bath PM; RIGHT-2 Investigators.. "Rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2". International Journal of Stroke. 2017. {{{volume}}}:1-16.

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.


No guidelines have incorporated findings to date – trial in follow-up.


  • 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)


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


  • 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


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


  • High stroke mimic rate reflects problems of paramedics rapidly identifying stroke at the stroke scene


  • British Heart Foundation
  • Conflict of interest: Author is Chief Investigator and grant holder

Further Reading