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)

Appleton, Jason P.; Scutt, Polly; Dixon, Mark; Howard, Harriet; Haywood, Lee; Havard, Diane; Hepburn, Trish; England, Timothy J.; Sprigg, Nikola; Woodhouse, Lisa J.; Wardlaw, Joanna M.; Montgomery, Alan A.; Pocock, Stuart J.; Bath, Philip M.W.

doi:10.1177/1747493017724627

Developing an adaptive platform trial for evaluation of medical treatments for Crohn’s disease (2025)
Journal Article
Noor, N. M., Radford, S. J., Choodari-Oskooei, B., Gordon, M., Hart, A. L., Hepburn, T., Juszczak, E., Lindsay, J. O., Kennedy, N. A., Parmar, M. K. B., Jairath, V., & Moran, G. W. (2025). Developing an adaptive platform trial for evaluation of medical treatments for Crohn’s disease. Nature Reviews Gastroenterology and Hepatology, 22, 364-366. https://doi.org/10.1038/s41575-025-01052-0

There is emerging interest in adaptive platform trials for inflammatory bowel disease. In this Comment, we present the results of a workshop that was convened to consider the opportunities and challenges of developing a platform trial in Crohn’s dise... Read More about Developing an adaptive platform trial for evaluation of medical treatments for Crohn’s disease.

A multifaceted and standardized approach is needed to improve acne severity assessment in clinical practice: an online survey of UK health professionals (2024)
Journal Article
Masterson, N., Burden-Teh, E., Healy, E., Hepburn, T., Layfield, C., Layton, A., Leighton, P., Leng, S., Mitchell, E., Northover, G., Penzer-Hick, R., Price, W., Radley, K., Ramesh, G., Ravenscroft, J. C., Sach, T., Sadiq, S., Santer, M., Thomas, K. S., Thompson, A., …the Acne-ID Trial Development Team. (2025). A multifaceted and standardized approach is needed to improve acne severity assessment in clinical practice: an online survey of UK health professionals. Clinical and Experimental Dermatology, 50(1), 158-160. https://doi.org/10.1093/ced/llae180

Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial (2023)
Journal Article
Desborough, M. J. R., Al-Shahi Salman, R., Stanworth, S. J., Havard, D., Woodhouse, L. J., Craig, J., Krishnan, K., Brennan, P. M., Dineen, R. A., Coats, T. J., Hepburn, T., Bath, P. M., Sprigg, N., & for DASH trial investigators, F. D. T. I. (2023). Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial. Lancet Neurology, 22(7), 557-567. https://doi.org/10.1016/S1474-4422%2823%2900157-6

Background: The risk of death from spontaneous intracerebral haemorrhage is increased for people taking antiplatelet drugs. We aimed to assess the feasibility of randomising patients on antiplatelet drug therapy with spontaneous intracerebral haemorr... Read More about Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial.

Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT (2022)
Journal Article
Armstrong-Buisseret, L., Brittain, C., Kai, J., David, M., Anstey Watkins, J., Ozolins, M., Jackson, L., Abdali, Z., Hepburn, T., Griffiths, F., Montgomery, A., Daniels, J., Manley, A., Dean, G., & Ross, J. D. (2022). Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT. Health Technology Assessment, 26(2), 1-170. https://doi.org/10.3310/ZZKH4176

BACKGROUND: Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur. OBJECTIVES: The... Read More about Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT.

The DEVA trial: protocol for a randomised controlled trial of dequalinium chloride versus usual care antibiotics for the treatment of bacterial vaginosis (2021)
Journal Article
Haydock, R., Hepburn, T., Ross, J., Daniels, J., Brittain, C., Jackson, L., Ozolins, M., & Wilson, J. (2021). The DEVA trial: protocol for a randomised controlled trial of dequalinium chloride versus usual care antibiotics for the treatment of bacterial vaginosis. Trials, 23(1), Article 1040. https://doi.org/10.1186/s13063-022-06954-x

Background: Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women of reproductive age, and it is estimated that up to a third of women will experience it at some point in their lives. BV produces an offensive vaginal odour a... Read More about The DEVA trial: protocol for a randomised controlled trial of dequalinium chloride versus usual care antibiotics for the treatment of bacterial vaginosis.

Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH): protocol for a phase II double blind randomised controlled feasibility trial (2020)
Journal Article
Desborough, M. J., Al-Shahi Salman, R., Stanworth, S. J., Havard, D., Brennan, P. M., Dineen, R. A., Coats, T. J., Hepburn, T., Bath, P. M., Sprigg, N., & DASH trial investigators. (2020). Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH): protocol for a phase II double blind randomised controlled feasibility trial. BMJ Open, 10(11), Article e037555. https://doi.org/10.1136/bmjopen-2020-037555

Introduction Intracerebral haemorrhage (ICH) can be devastating and is a common cause of death and disability worldwide. Pre-ICH antiplatelet drug use is associated with a 27% relative increase in 1 month case fatality compared with patients not usin... Read More about Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH): protocol for a phase II double blind randomised controlled feasibility trial.

Protocol for a multi-centre randomised controlled stand-alone feasibility trial to assess potential effectiveness and cost-effectiveness of digital hearing aids in patients with tinnitus and hearing loss (the HUSH trial) (2020)
Journal Article
Haines, R., White, J., Meakin, G., Tan, W., Hepburn, T., Leighton, P., Hall, D., & Sereda, M. (2020). Protocol for a multi-centre randomised controlled stand-alone feasibility trial to assess potential effectiveness and cost-effectiveness of digital hearing aids in patients with tinnitus and hearing loss (the HUSH trial). Pilot and Feasibility Studies, 6, Article 41. https://doi.org/10.1186/s40814-020-00582-5

Background: The most common management strategy for tinnitus provided in UK audiology clinics is education and advice. This may also be combined with some form of sound therapy (e.g. digital hearing aids). While education and advice is generally prov... Read More about Protocol for a multi-centre randomised controlled stand-alone feasibility trial to assess potential effectiveness and cost-effectiveness of digital hearing aids in patients with tinnitus and hearing loss (the HUSH trial).

A randomised feasibility trial comparing needle fasciotomy with limited fasciectomy treatment for Dupuytren’s contractures (2020)
Journal Article
the HAND-1 Study group, Davis, T. R. C., Tan, W., Harrison, E. F., Hollingworth, W., Karantana, A., Mills, N., Hepburn, T., Sprange, K., Duley, L., Blazeby, J. M., Bainbridge, C. G., Murali, R., & Montgomery, A. A. (2020). A randomised feasibility trial comparing needle fasciotomy with limited fasciectomy treatment for Dupuytren’s contractures. Pilot and Feasibility Studies, 6(1), Article 7. https://doi.org/10.1186/s40814-019-0546-y

© 2020 The Author(s). Purpose: The purpose of this study is to assess the feasibility of conducting a large, multicentre randomised controlled trial (RCT) comparing needle fasciotomy with limited fasciectomy for treatment of Dupuytren's contractures.... Read More about A randomised feasibility trial comparing needle fasciotomy with limited fasciectomy treatment for Dupuytren’s contractures.

Metronidazole versus lactic acid for treating bacterial vaginosis (VITA): protocol for a randomised controlled trial to assess the clinical and cost effectiveness of topical lactic acid gel for treating second and subsequent episodes of bacterial vaginosis (2019)
Journal Article
Armstrong-Buisseret, L., Brittain, C., David, M., Dean, G., Griffiths, F., Hepburn, T., Jackson, L., Kai, J., Montgomery, A., Roberts, T., Thandi, S., & Ross, J. D. (2019). Metronidazole versus lactic acid for treating bacterial vaginosis (VITA): protocol for a randomised controlled trial to assess the clinical and cost effectiveness of topical lactic acid gel for treating second and subsequent episodes of bacterial vaginosis. Trials, 20, Article 648. https://doi.org/10.1186/s13063-019-3731-7

Background: Bacterial vaginosis (BV) affects 30 – 50% of women at some time in their lives and is an embarrassing and distressing condition which can be associated with potentially serious comorbidities. Current antibiotic treatments such as metronid... Read More about Metronidazole versus lactic acid for treating bacterial vaginosis (VITA): protocol for a randomised controlled trial to assess the clinical and cost effectiveness of topical lactic acid gel for treating second and subsequent episodes of bacterial vaginosis.

Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea; the relationship between antibiotic minimum inhibitory concentration and clinical outcome (2019)
Journal Article
Cole, M., Tan, W., Fifer, H., Brittain, C., Duley, L., Hepburn, T., Lawrence, T., Montgomery, A., SPRANGE, K., Thandi, S., Churchward, C., Tripodo, F., Woodford, N., & Ross, J. (2020). Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea; the relationship between antibiotic minimum inhibitory concentration and clinical outcome. Journal of Antimicrobial Chemotherapy, 75(2), 449–457. https://doi.org/10.1093/jac/dkz436

© Crown copyright 2019. OBJECTIVES: To investigate the relationship between MIC and clinical outcome in a randomized controlled trial that compared gentamicin 240 mg plus azithromycin 1 g with ceftriaxone 500 mg plus azithromycin 1 g. MIC analysis wa... Read More about Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea; the relationship between antibiotic minimum inhibitory concentration and clinical outcome.

Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage (2019)
Journal Article
Bath, P. M., Woodhouse, L. J., Krishnan, K., Appleton, J. P., Anderson, C. S., Berge, E., Cala, L., Dixon, M., England, T. J., Godolphin, P. J., Hepburn, T., Mair, G., Montgomery, A. A., Phillips, S. J., Potter, J., Price, C. I., Randall, M., Robinson, T. G., Roffe, C., Rothwell, P. M., …Sprigg, N. (2019). Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage. Stroke, 50(11), 3064-3071. https://doi.org/10.1161/STROKEAHA.119.026389

Background and Purpose—
Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset.

Methods—
We undertook a multicentre, paramedic-delivered, ambulance-based, prospective ran... Read More about Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage.

Eicosapentaenoic acid and/or aspirin for preventing colorectal adenomas during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: the seAFOod RCT (2019)
Journal Article
Hull, M. A., Sprange, K., Hepburn, T., Tan, W., Shafayat, A., Rees, C. J., Clifford, G., Logan, R. F., Loadman, P. M., Williams, E. A., Whitham, D., & Montgomery, A. A. (2019). Eicosapentaenoic acid and/or aspirin for preventing colorectal adenomas during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: the seAFOod RCT. Efficacy and Mechanism Evaluation, 6(4), 1-154. https://doi.org/10.3310/eme06040

Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial (2019)
Journal Article
Ross, J., Brittain, C., Cole, M., Dewsnap, C., Harding, J., Hepburn, T., Jackson, L., Keogh, M., Lawrence, T., Montgomery, A., Roberts, T. E., SPRANGE, K., Tan, W., Thandi, S., White, J., Wilson, J., & Duley, L. (2019). Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial. Lancet, 393(10190), 2511-2520. https://doi.org/10.1016/S0140-6736%2818%2932817-4

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Background: Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimi... Read More about Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial.

Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT (2019)
Journal Article
Ross, J. D., Harding, J., Duley, L., Montgomery, A. A., Hepburn, T., Tan, W., Brittain, C., Meakin, G., Sprange, K., Thandi, S., Jackson, L., Roberts, T., Wilson, J., White, J., Dewsnap, C., Cole, M., & Lawrence, T. (2019). Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT. Health Technology Assessment, 23(20), 1-104. https://doi.org/10.3310/hta23200

Background: Gonorrhoea is a common sexually transmitted infection that can cause pain and discomfort, affect fertility in women and lead to epididymo-orchitis in men. Current treatment is with ceftriaxone, but there is increasing evidence of antimicr... Read More about Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT.

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial (2019)
Journal Article
Bath, P. M., Scutt, P., Anderson, C. S., Appleton, J. P., Berge, E., Cala, L., Dixon, M., England, T. M., Godolphin, P. J., Havard, D., Haywood, L., Hepburn, T., Krishnan, K., Mair, G., Montgomery, A. A., Muir, K., Phillips, S. J., Pocock, S., Potter, J., Price, C., …Mir, R. (2019). Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial. Lancet, 393(10175), 1009-1020. https://doi.org/10.1016/S0140-6736%2819%2930194-1

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure... Read More about Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial.

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial (2018)
Journal Article
Hull, M. A., Sprange, K., Hepburn, T., Tan, W., Shafayat, A., Rees, C. J., Clifford, G., Logan, R. F., Loadman, P. M., Williams, E. A., Whitham, D., Montgomery, A. A., & seAFOod Collaborative Group. (2018). Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial. Lancet, 392(10164), 2583-2594. https://doi.org/10.1016/S0140-6736%2818%2931775-6

© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Background
The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer... Read More about Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial.

Central masked adjudication of stroke diagnosis at trial entry offered no advantage over diagnosis by local clinicians: secondary analysis and simulation (2018)
Journal Article
Godolphin, P., Hepburn, T., Sprigg, N., Walker, L., Berge, E., Collins, R., Gommans, J., Ntaios, G., Pocock, S., Prasad, K., Wardlaw, J., Bath, P., & Montgomery, A. (2018). Central masked adjudication of stroke diagnosis at trial entry offered no advantage over diagnosis by local clinicians: secondary analysis and simulation. Contemporary Clinical Trials Communications, 12, 176-181. https://doi.org/10.1016/j.conctc.2018.11.002

Background

Central adjudication of stroke type is commonly implemented in large multicentre clinical trials. We investigated the effect of central adjudication of diagnosis of stroke type at trial entry in the Efficacy of Nitric Oxide in Stroke (E... Read More about Central masked adjudication of stroke diagnosis at trial entry offered no advantage over diagnosis by local clinicians: secondary analysis and simulation.

Reduced fetal movement intervention Trial-2 (ReMIT-2): protocol for a pilot randomised controlled trial of standard care informed by the result of a placental growth factor (PlGF) blood test versus standard care alone in women presenting with reduced fetal movement at or after 36+ 0 weeks gestation (2018)
Journal Article
Armstrong-Buisseret, L., Mitchell, E., Hepburn, T., Duley, L., Thornton, J. G., Roberts, T. E., Storey, C., Smyth, R., & Heazell, A. E. P. (2018). Reduced fetal movement intervention Trial-2 (ReMIT-2): protocol for a pilot randomised controlled trial of standard care informed by the result of a placental growth factor (PlGF) blood test versus standard care alone in women presenting with reduced fetal movement at or after 36+ 0 weeks gestation. Trials, 19, 1-13. https://doi.org/10.1186/s13063-018-2859-1

Background:
Forty percent of babies who are stillborn born die after 36 weeks gestation and have no lethal structural abnormality. Maternal perception of reduced fetal movement (RFM) is associated with stillbirth and is related to abnormal placental... Read More about Reduced fetal movement intervention Trial-2 (ReMIT-2): protocol for a pilot randomised controlled trial of standard care informed by the result of a placental growth factor (PlGF) blood test versus standard care alone in women presenting with reduced fetal movement at or after 36+ 0 weeks gestation.

Home interventions and light therapy for treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomized controlled trial (2018)
Journal Article
Haines, R. H., Thomas, K. S., Montgomery, A. A., Ravenscroft, J. C., Akram, P., Chalmers, J., Whitman, D., Duley, L., Eleftheriadou, V., Meakin, G., Mitchell, E., White, J., Rogers, A., Sach, T., Santer, M., Tan, W., Hepburn, T., Williams, H. C., & Batchelor, J. M. (2018). Home interventions and light therapy for treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomized controlled trial. BMJ Open, 8(4), Article e018649. https://doi.org/10.1136/bmjopen-2017-018649

Vitiligo is a condition resulting in white patches on the skin. People with vitiligo can suffer from low self-esteem, psychological disturbance and diminished quality of life. Vitiligo is often poorly managed, partly due to lack of high quality evide... Read More about Home interventions and light therapy for treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomized controlled trial.

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) (2017)
Journal Article
Appleton, J. P., Scutt, P., Dixon, M., Howard, H., Haywood, L., Havard, D., Hepburn, T., England, T. J., Sprigg, N., Woodhouse, L. J., Wardlaw, J. M., Montgomery, A. A., Pocock, S. J., & Bath, P. M. (in press). 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). International Journal of Stroke, https://doi.org/10.1177/1747493017724627

Rationale: Vascular nitric oxide levels are low in acute stroke and donors such as glyceryl trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombol... Read More about 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).

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