Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2022

Open Access 01-12-2022 | Bosentan | Study protocol

Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)—a multicentre randomised controlled trial protocol

Authors: Christophe Chiquet, Catherine Vignal, Philippe Gohier, Emmanuel Heron, Gilles Thuret, Marie Bénédicte Rougier, Audrey Lehmann, Laurent Flet, Jean-Louis Quesada, Mathieu Roustit, Dan Milea, Jean-Louis Pepin, For the ENDOTHELION group

Published in: Trials | Issue 1/2022

Login to get access

Abstract

Background

Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients.

Methods

ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process.

Discussion

An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population.

Trial registration

ClinicalTrials.gov NCT02377271. Registered on March 3, 2015.
Literature
1.
Lee MS, Grossman D, Arnold AC, Sloan FA. Incidence of nonarteritic anterior ischemic optic neuropathy: increased risk among diabetic patients. Ophthalmology. 2011;118:959–63.PubMedCrossRef
2.
3.
Mentek M, Aptel F, Godin-Ribuot D, Tamisier R, Pepin J-L, Chiquet C. Diseases of the retina and the optic nerve associated with obstructive sleep apnea. Sleep Med Rev. 2018;38:113–30.PubMedCrossRef
4.
Wu Y, Zhou L-M, Lou H, Cheng J-W, Wei R-L. The association between obstructive sleep apnea and nonarteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis. Curr Eye Res. 2016;41:987–92.PubMedCrossRef
5.
Mojon DS, Hedges TR, Ehrenberg B, Karam EZ, Goldblum D, Abou-Chebl A, et al. Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2002;120:601–5.PubMedCrossRef
6.
Palombi K, Renard E, Levy P, Chiquet C, Deschaux C, Romanet JP, et al. Non-arteritic anterior ischaemic optic neuropathy is nearly systematically associated with obstructive sleep apnoea. Br J Ophthalmol. 2006;90:879–82.PubMedPubMedCentralCrossRef
7.
Guyer DR, Miller NR, Auer CL, Fine SL. The risk of cerebrovascular and cardiovascular disease in patients with anterior ischemic optic neuropathy. Arch Ophthalmol. 1985;103:1136–42.PubMedCrossRef
8.
Hayreh SS, Joos KM, Podhajsky PA, Long CR. Systemic diseases associated with nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 1994;118:766–80.PubMedCrossRef
9.
Repka MX, Savino PJ, Schatz NJ, Sergott RC. Clinical profile and long-term implications of anterior ischemic optic neuropathy. Am J Ophthalmol. 1983;96:478–83.PubMedCrossRef
10.
Giambene B, Sodi A, Sofi F, Marcucci R, Fedi S, Abbate R, et al. Evaluation of traditional and emerging cardiovascular risk factors in patients with non-arteritic anterior ischemic optic neuropathy: a case-control study. Graefes Arch Clin Exp Ophthalmol. 2009;247:693–7.PubMedCrossRef
11.
Salomon O, Huna-Baron R, Kurtz S, Steinberg DM, Moisseiev J, Rosenberg N, et al. Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 1999;106:739–42.PubMedCrossRef
12.
Doro S, Lessell S. Cup-disc ratio and ischemic optic neuropathy. Arch Ophthalmol. 1985;103:1143–4.PubMedCrossRef
13.
Beck RW, Savino PJ, Repka MX, Schatz NJ, Sergott RC. Optic disc structure in anterior ischemic optic neuropathy. Ophthalmology. 1984;91:1334–7.PubMedCrossRef
14.
Burde RM. Optic disk risk factors for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 1993;116:759–64.PubMedCrossRef
15.
Feit RH, Tomsak RL, Ellenberger C. Structural factors in the pathogenesis of ischemic optic neuropathy. Am J Ophthalmol. 1984;98:105–8.PubMedCrossRef
16.
Hayreh SS, Zimmerman MB. Nonarteritic anterior ischemic optic neuropathy: natural history of visual outcome. Ophthalmology. 2008;115:298–305.e2.PubMedCrossRef
17.
Scherer RW, Feldon SE, Levin L, Langenberg P, Katz J, Keyl PM, et al. Visual fields at follow-up in the Ischemic Optic Neuropathy Decompression Trial: evaluation of change in pattern defect and severity over time. Ophthalmology. 2008;115:1809–17.PubMedCrossRef
18.
Johnson LN, Guy ME, Krohel GB, Madsen RW. Levodopa may improve vision loss in recent-onset, nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2000;107:521–6.PubMedCrossRef
19.
Hayreh SS. Treatment of non-arteritic anterior ischemic optic neuropathy with high-dose systemic corticosteroid therapy. Graefes Arch Clin Exp Ophthalmol. 2013;251:1029–30.PubMedCrossRef
20.
Hayreh SS, Zimmerman MB. Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid therapy. Graefes Arch Clin Exp Ophthalmol. 2008;246:1029–46.PubMedPubMedCentralCrossRef
21.
Pakravan M, Sanjari N, Esfandiari H, Pakravan P, Yaseri M. The effect of high-dose steroids, and normobaric oxygen therapy, on recent onset non-arteritic anterior ischemic optic neuropathy: a randomized clinical trial. Graefes Arch Clin Exp Ophthalmol. 2016;254:2043–8.PubMedCrossRef
22.
Saxena R, Singh D, Sharma M, James M, Sharma P, Menon V. Steroids versus no steroids in nonarteritic anterior ischemic optic neuropathy: a randomized controlled trial. Ophthalmology. 2018;125:1623–7.PubMedCrossRef
23.
Rebolleda G, Pérez-López M, Casas-LLera P, Contreras I, Muñoz-Negrete FJ. Visual and anatomical outcomes of non-arteritic anterior ischemic optic neuropathy with high-dose systemic corticosteroids. Graefes Arch Clin Exp Ophthalmol. 2013;251:255–60.PubMedCrossRef
24.
Modarres M, Sanjari MS, Falavarjani KG. Vitrectomy and release of presumed epipapillary vitreous traction for treatment of nonarteritic anterior ischemic optic neuropathy associated with partial posterior vitreous detachment. Ophthalmology. 2007;114:340–4.PubMedCrossRef
25.
26.
Durbant E, Radoi C, Garcia T, Denoyer A, Arndt C. Intravitreal triamcinolone injections in non-arteritic anterior ischemic optic neuropathy - a retrospective report. J Fr Ophtalmol. 2021;44:777–85.PubMedCrossRef
27.
Jonas JB, Spandau UH, Harder B, Sauder G. Intravitreal triamcinolone acetonide for treatment of acute nonarteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2007;245:749–50.PubMedCrossRef
28.
Fujikado T, Morimoto T, Matsushita K, Shimojo H, Okawa Y, Tano Y. Effect of transcorneal electrical stimulation in patients with nonarteritic ischemic optic neuropathy or traumatic optic neuropathy. Jpn J Ophthalmol. 2006;50:266–73.PubMedCrossRef
29.
Wilhelm B, Lüdtke H, Wilhelm H, BRAION Study Group. Efficacy and tolerability of 0.2% brimonidine tartrate for the treatment of acute non-arteritic anterior ischemic optic neuropathy (NAION): a 3-month, double-masked, randomised, placebo-controlled trial. Graefes Arch Clin Exp Ophthalmol. 2006;244:551–8.PubMedCrossRef
30.
Guerriero S, Giancipoli G, Cantatore A, Sacco G, Brescia P, Saliani MT, et al. LDL apheresis in the treatment of non-arteritic ischaemic optic neuropathy: a 6-month follow-up study. Eye (Lond). 2009;23:1343–4.CrossRef
31.
Modarres M, Falavarjani KG, Nazari H, Sanjari MS, Aghamohammadi F, Homaii M, et al. Intravitreal erythropoietin injection for the treatment of non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol. 2011;95:992–5.PubMedCrossRef
32.
Saatci AO, Taskin O, Selver OB, Yaman A, Bajin MS. Efficacy of intravitreal ranibizumab injection in acute nonarteritic ischemic optic neuropathy: a long-term follow up. Open Ophthalmol J. 2013;7:58–62.PubMedPubMedCentralCrossRef
33.
Radoi C, Garcia T, Brugniart C, Ducasse A, Arndt C. Intravitreal triamcinolone injections in non-arteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2014;252:339–45.PubMedCrossRef
34.
Rootman DB, Gill HS, Margolin EA. Intravitreal bevacizumab for the treatment of nonarteritic anterior ischemic optic neuropathy: a prospective trial. Eye (Lond). 2013;27:538–44.CrossRef
35.
Prokosch V, Thanos S. Visual outcome of patients following NAION after treatment with adjunctive fluocortolone. Restor Neurol Neurosci. 2014;32:381–9.PubMed
36.
Kinori M, Ben-Bassat I, Wasserzug Y, Chetrit A, Huna-Baron R. Visual outcome of mega-dose intravenous corticosteroid treatment in non-arteritic anterior ischemic optic neuropathy - retrospective analysis. BMC Ophthalmol. 2014;14:62.PubMedPubMedCentralCrossRef
37.
Zhu W, Liao R, Chen Y, Liu L, Zhang Y. Effect of enhanced extracorporeal counterpulsation in patients with non-arteritic anterior ischaemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2015;253:127–33.PubMedCrossRef
38.
Lyttle DP, Johnson LN, Margolin EA, Madsen RW. Levodopa as a possible treatment of visual loss in nonarteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2016;254:757–64.PubMedCrossRef
39.
Sanjari N, Pakravan M, Nourinia R, Esfandiari H, Hafezi-Moghadam A, Zandi S, et al. Intravitreal injection of a rho-kinase inhibitor (Fasudil) for recent-onset nonarteritic anterior ischemic optic neuropathy. J Clin Pharmacol. 2016;56:749–53.PubMedCrossRef
40.
Aftab AM, Iqbal M, Rauf A, Ali A. Non arteritic anterior ischemic optic neuropathy; does anticoagulation help? J Ayub Med Coll Abbottabad. 2016;28:776–80 PMID: 28586576.PubMed
41.
Weiss JN, Levy S, Benes SC. Stem cell ophthalmology treatment study: bone marrow derived stem cells in the treatment of non-arteritic ischemic optic neuropathy (NAION). Stem Cell Investig. 2017;4:94.PubMedPubMedCentralCrossRef
42.
Pakravan M, Esfandiari H, Hassanpour K, Razavi S, Pakravan P. The effect of combined systemic erythropoietin and steroid on non-arteritic anterior ischemic optic neuropathy: a prospective study. Curr Eye Res. 2017;42:1079–84.PubMedCrossRef
43.
Kalábová S, Marešová K, Karhanová M. Non-arteritic anterior ischaemic optic neuropathy: treatment and risk factors. Cesk Slov Oftalmol. 2020;76:78–87.PubMed
44.
Nikkhah H, Golalipour M, Doozandeh A, Pakravan M, Yaseri M, Esfandiari H. The effect of systemic erythropoietin and oral prednisolone on recent-onset non-arteritic anterior ischemic optic neuropathy: a randomized clinical trial. Graefes Arch Clin Exp Ophthalmol. 2020;258:2291–7.PubMedCrossRef
45.
Chang MY, Keltner JL. Risk factors for fellow eye involvement in nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2019;39:147–52.PubMedCrossRef
46.
Newman NJ, Scherer R, Langenberg P, Kelman S, Feldon S, Kaufman D, et al. The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol. 2002;134:317–28.PubMedCrossRef
47.
Aptel F, Khayi H, Pépin J-L, Tamisier R, Levy P, Romanet J-P, et al. Association of nonarteritic ischemic optic neuropathy with obstructive sleep apnea syndrome: consequences for obstructive sleep apnea screening and treatment. JAMA Ophthalmol. 2015;133:797–804.PubMedCrossRef
48.
Fraser CL. Update on obstructive sleep apnea for neuro-ophthalmology. Curr Opin Neurol. 2019;32:124–30.PubMedCrossRef
49.
Sun M-H, Lee C-Y, Liao YJ, Sun C-C. Nonarteritic anterior ischaemic optic neuropathy and its association with obstructive sleep apnoea: a health insurance database study. Acta Ophthalmol. 2019;97:e64–70.PubMedCrossRef
50.
Belaidi E, Joyeux-Faure M, Ribuot C, Launois SH, Levy P, Godin-Ribuot D. Major role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea. J Am Coll Cardiol. 2009;53:1309–17.PubMedCrossRef
51.
Kanagy NL, Walker BR, Nelin LD. Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension. 2001;37:511–5.PubMedCrossRef
52.
Chauhan BC, LeVatte TL, Jollimore CA, Yu PK, Reitsamer HA, Kelly MEM, et al. Model of endothelin-1-induced chronic optic neuropathy in rat. Invest Ophthalmol Vis Sci. 2004;45:144–52.PubMedCrossRef
53.
Resch H, Karl K, Weigert G, Wolzt M, Hommer A, Schmetterer L, et al. Effect of dual endothelin receptor blockade on ocular blood flow in patients with glaucoma and healthy subjects. Invest Ophthalmol Vis Sci. 2009;50:358–63.PubMedCrossRef
54.
Humbert M, Segal ES, Kiely DG, Carlsen J, Schwierin B, Hoeper MM. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J. 2007;30:338–44.PubMedCrossRef
55.
García-Basterra I, García-Ben A, Ríus-Díaz F, González-Gómez A, Hedges TR, Vuong LN, et al. Prospective analysis of macular and optic disc changes after non-arteritic anterior ischemic optic neuropathy. J Fr Ophtalmol. 2020;43:35–42.PubMedCrossRef
56.
57.
Hayreh SS, Zimmerman MB. Optic disc edema in non-arteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2007;245:1107–21.PubMedCrossRef
58.
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD, et al. Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol. 2001;119:1050–8.PubMedCrossRef
59.
Weber C, Schmitt R, Birnboeck H, Hopfgartner G, Eggers H, Meyer J, et al. Multiple-dose pharmacokinetics, safety, and tolerability of bosentan, an endothelin receptor antagonist, in healthy male volunteers. J Clin Pharmacol. 1999;39:703–14.PubMedCrossRef
60.
Contreras I, Noval S, Rebolleda G, Muñoz-Negrete FJ. Follow-up of nonarteritic anterior ischemic optic neuropathy with optical coherence tomography. Ophthalmology. 2007;114:2338–44.PubMedCrossRef
61.
Bellusci C, Savini G, Carbonelli M, Carelli V, Sadun AA, Barboni P. Retinal nerve fiber layer thickness in nonarteritic anterior ischemic optic neuropathy: OCT characterization of the acute and resolving phases. Graefes Arch Clin Exp Ophthalmol. 2008;246:641–7.PubMedCrossRef
62.
Newman NJ. The ischemic optic neuropathy decompression trial. Arch Ophthalmol. 2007;125:1568–70 American Medical Association.PubMedCrossRef
63.
Han S, Jung JJ, Kim US. Differences between non-arteritic anterior ischemic optic neuropathy and open angle glaucoma with altitudinal visual field defect. Korean J Ophthalmol. 2015;29:418–23.PubMedPubMedCentralCrossRef
64.
Deleón-Ortega J, Carroll KE, Arthur SN, Girkin CA. Correlations between retinal nerve fiber layer and visual field in eyes with nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 2007;143:288–94.PubMedCrossRef
65.
Boone MI, Massry GG, Frankel RA, Holds JB, Chung SM. Visual outcome in bilateral nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 1996;103:1223–8.PubMedCrossRef
66.
Feldon SE. Computerized expert system for evaluation of automated visual fields from the ischemic optic neuropathy decompression trial: methods, baseline fields, and six-month longitudinal follow-up. Trans Am Ophthalmol Soc. 2004;102:269–304.PubMedPubMedCentral
67.
Hedges TR, Vuong LN, Gonzalez-Garcia AO, Mendoza-Santiesteban CE, Amaro-Quierza ML. Subretinal fluid from anterior ischemic optic neuropathy demonstrated by optical coherence tomography. Arch Ophthalmol. 2008;126:812–5.PubMedCrossRef
68.
Contreras I, Rebolleda G, Noval S, Muñoz-Negrete FJ. Optic disc evaluation by optical coherence tomography in nonarteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2007;48:4087–92.PubMedCrossRef
69.
70.
Beck RW, Servais GE, Hayreh SS. Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. Ophthalmology. 1987;94:1503–8.PubMedCrossRef
71.
Arnold AC. Pathogenesis of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2003;23:157–63.PubMedCrossRef
72.
Wheeler LA, Lai R, Woldemussie E. From the lab to the clinic: activation of an alpha-2 agonist pathway is neuroprotective in models of retinal and optic nerve injury. Eur J Ophthalmol. 1999;9(Suppl 1):S17–21.PubMedCrossRef
73.
Levkovitch-Verbin H, Harris-Cerruti C, Groner Y, Wheeler LA, Schwartz M, Yoles E. RGC death in mice after optic nerve crush injury: oxidative stress and neuroprotection. Invest Ophthalmol Vis Sci. 2000;41:4169–74 PMID: 11095611.PubMed
74.
Yoles E, Wheeler LA, Schwartz M. Alpha2-adrenoreceptor agonists are neuroprotective in a rat model of optic nerve degeneration. Invest Ophthalmol Vis Sci. 1999;40:65–73 PMID: 9888428.PubMed
75.
Gottlob I, Weghaupt H, Vass C. Effect of levodopa on the human luminance electroretinogram. Invest Ophthalmol Vis Sci. 1990;31:1252–8 PMID: 2365557.PubMed
76.
Kupersmith MJ, Miller NR. A nonarteritic anterior ischemic optic neuropathy clinical trial: an industry and NORDIC collaboration. J Neuroophthalmol. 2016;36:235–7.PubMedCrossRef
77.
Schuff-Werner P, Schütz E, Seyde WC, Eisenhauer T, Janning G, Armstrong VW, et al. Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin-induced extracorporeal LDL precipitation (HELP). Eur J Clin Invest. 1989;19:30–7.PubMed
78.
Haas A, Walzl M, Jesenik F, Walzl B, Berghold A, Berglöff J, et al. Application of HELP in nonarteritic anterior ischemic optic neuropathy: a prospective, randomized, controlled study. Graefes Arch Clin Exp Ophthalmol. 1997;235:14–9.PubMedCrossRef
79.
Polak K, Petternel V, Luksch A, Krohn J, Findl O, Polska E, et al. Effect of endothelin and BQ123 on ocular blood flow parameters in healthy subjects. Invest Ophthalmol Vis Sci. 2001;42:2949–56 PMID: 11687541.PubMed
80.
Packer M, McMurray JJV, Krum H, Kiowski W, Massie BM, Caspi A, et al. Long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure: primary results of the ENABLE Trials. JACC Heart Fail. 2017;5:317–26.PubMedCrossRef
81.
McLaughlin VV, Sitbon O, Badesch DB, Barst RJ, Black C, Galiè N, et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J. 2005;25:244–9.PubMedCrossRef
Metadata
Title
Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)—a multicentre randomised controlled trial protocol
Authors
Christophe Chiquet
Catherine Vignal
Philippe Gohier
Emmanuel Heron
Gilles Thuret
Marie Bénédicte Rougier
Audrey Lehmann
Laurent Flet
Jean-Louis Quesada
Mathieu Roustit
Dan Milea
Jean-Louis Pepin
For the ENDOTHELION group
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-022-06786-9

Other articles of this Issue 1/2022

Trials 1/2022 Go to the issue

Study protocol

Efficacy and safety of piezocision in accelerating maxillary anterior teeth en-masse retraction: study protocol for a randomized controlled trial

Study protocol

Safety and effectiveness of delivering mass drug administration for helminths through the seasonal malaria chemoprevention platform among Senegalese children: study protocol for a randomised controlled trial

Research

Underrepresentation of ethnic minorities in hypertension research—a survey of enablers and barriers among South Asian and African communities in Glasgow

Study protocol

Awakening the control of the ankle dorsiflexors in the post-stroke hemiplegic subject to improve walking activity and social participation: the WAKE (Walking Ankle isoKinetic Exercise) randomised, controlled trial

Study protocol

Effect of vaginal antiseptic prior to caesarean section on the rate of post-caesarean complications: a blinded randomised controlled trial

Study protocol

ANDA-Evaluating Facilitated Feedback Enhancement - a Cluster randomised Trial (ANDA-EFFECT): protocol for a cluster randomised trial of audit feedback augmented with education and support, compared to feedback alone, on acceptability, utility and health outcomes in diabetes centres in Australia