Efficacy and safety of systemic, high-dose glucocorticoid therapy for idiopathic sudden sensorineural hearing loss : Study protocol for a three-armed, randomized, triple-blind, multicenter trial (HODOKORT).
Wirksamkeit und Sicherheit der systemischen Hochdosis-Glukokortikoidtherapie beim akuten idiopathischen sensorineuralen Hörverlust (Hörsturz) : Studienprotokoll für eine dreiarmige, randomisierte, dreifach verblindete Multizenterstudie (HODOKORT).
Corticosteroids
Dexamethasone
Glucocorticoids
Humans
Idiopathic
Prednisolone
Randomized controlled trial
Steroids
Sudden hearing loss
Journal
HNO
ISSN: 1433-0458
Titre abrégé: HNO
Pays: Germany
ID NLM: 2985099R
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
accepted:
09
05
2022
pubmed:
21
6
2022
medline:
8
7
2022
entrez:
20
6
2022
Statut:
ppublish
Résumé
Systemic glucocorticosteroids ("steroids") are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids without evidence from randomized controlled trials (RCTs) and refers solely to retrospective cohort studies. This RCT aims to assess the efficacy (improvement in hearing) and safety (especially systemic side effects) of high-dose steroids versus standard of care (standard dose systemic steroids) for the treatment of unilateral ISSHL, when given as a primary therapy. The study is designed as a multicenter (approximately 40 centers), randomized, triple-blind, three-armed, parallel group, clinical trial with 312 adult patients. The interventions consist of 5 days of 250 mg/day intravenous prednisolone (intervention 1) + oral placebo, or 5 days of 40 mg/day oral dexamethasone (intervention 2) + intravenous placebo. The control intervention consists of 60 mg oral prednisolone for 5 days followed by five tapering doses + intravenous placebo. The primary efficacy endpoint is the change in hearing threshold in the three most affected contiguous frequencies between 0.25 and 8 kHz 1 month after ISSHL. Secondary endpoints include further measures of hearing improvement including speech audiometry, tinnitus, quality of life, blood pressure, and altered glucose tolerance. There is an unmet medical need for an effective medical therapy of ISSHL. Although sensorineural hearing impairment can be partially compensated by hearing aids or cochlear implants (CI), generic hearing is better than using hearing aids or CIs. Since adverse effects of a short course of high-dose systemic corticosteroids have not been documented with good evidence, the trial will improve knowledge on possible side effects in the different treatment arms with a focus on hyperglycemia and hypertension. EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) Nr. 2015-002602-36; Sponsor code: KKSH-127.
Sections du résumé
BACKGROUND
BACKGROUND
Systemic glucocorticosteroids ("steroids") are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids without evidence from randomized controlled trials (RCTs) and refers solely to retrospective cohort studies. This RCT aims to assess the efficacy (improvement in hearing) and safety (especially systemic side effects) of high-dose steroids versus standard of care (standard dose systemic steroids) for the treatment of unilateral ISSHL, when given as a primary therapy.
METHODS
METHODS
The study is designed as a multicenter (approximately 40 centers), randomized, triple-blind, three-armed, parallel group, clinical trial with 312 adult patients. The interventions consist of 5 days of 250 mg/day intravenous prednisolone (intervention 1) + oral placebo, or 5 days of 40 mg/day oral dexamethasone (intervention 2) + intravenous placebo. The control intervention consists of 60 mg oral prednisolone for 5 days followed by five tapering doses + intravenous placebo. The primary efficacy endpoint is the change in hearing threshold in the three most affected contiguous frequencies between 0.25 and 8 kHz 1 month after ISSHL. Secondary endpoints include further measures of hearing improvement including speech audiometry, tinnitus, quality of life, blood pressure, and altered glucose tolerance.
DISCUSSION
CONCLUSIONS
There is an unmet medical need for an effective medical therapy of ISSHL. Although sensorineural hearing impairment can be partially compensated by hearing aids or cochlear implants (CI), generic hearing is better than using hearing aids or CIs. Since adverse effects of a short course of high-dose systemic corticosteroids have not been documented with good evidence, the trial will improve knowledge on possible side effects in the different treatment arms with a focus on hyperglycemia and hypertension.
TRIAL REGISTRATION
BACKGROUND
EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) Nr. 2015-002602-36; Sponsor code: KKSH-127.
Identifiants
pubmed: 35725822
doi: 10.1007/s00106-022-01184-8
pii: 10.1007/s00106-022-01184-8
pmc: PMC9208545
doi:
Substances chimiques
Glucocorticoids
0
Dexamethasone
7S5I7G3JQL
Prednisolone
9PHQ9Y1OLM
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
30-44Informations de copyright
© 2022. The Author(s).
Références
Alexiou C, Arnold W, Fauser C et al (2001) Sudden sensorineural hearing loss: Does application of glucocorticoids make sense? Arch Otolaryngol Head Neck Surg 127:253–258
doi: 10.1001/archotol.127.3.253
pubmed: 11255468
Ascaso JF, Pardo S, Real JT et al (2003) Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 26:3320–3325
doi: 10.2337/diacare.26.12.3320
pubmed: 14633821
AWMF (2014) Leitlinie Hörsturz (Akuter idiopathischer sensorineuraler Hörverlust) der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. https://www.awmf.org/leitlinien/detail/ll/017-010.html . Accessed 8 May 2022 (AWMF-Reg.-Nr. 017/010)
Burschka MA, Hassan HA, Reineke T et al (2001) Effect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients. Eur Arch Otorhinolaryngol 258:213–219
doi: 10.1007/s004050100343
pubmed: 11548897
Byl FM (1977) Seventy-six cases of presumed sudden hearing loss occurring in 1973: prognosis and incidence. Laryngoscope 87:817–825
doi: 10.1002/lary.5540870515
pubmed: 850455
Chan AW, Tetzlaff JM, Altman DG et al (2013) SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 158:200–207
doi: 10.7326/0003-4819-158-3-201302050-00583
pubmed: 23295957
pmcid: 5114123
Clark JG (1981) Uses and abuses of hearing loss classification. Asha 23:493–500
pubmed: 7052898
GBD 2019 Hearing Loss Collaborators (2021) Hearing loss prevalence and years lived with disability, 1990–2019: findings from the Global Burden of Disease Study 2019. Lancet 397:996–1009
doi: 10.1016/S0140-6736(21)00516-X
Conlin AE, Parnes LS (2007) Treatment of sudden sensorineural hearing loss: II. A meta-analysis. Arch Otolaryngol Head Neck Surg 133:582–586
doi: 10.1001/archotol.133.6.582
pubmed: 17576909
Crane RA, Camilon M, Nguyen S et al (2015) Steroids for treatment of sudden sensorineural hearing loss: a meta-analysis of randomized controlled trials. Laryngoscope 125:209–217
doi: 10.1002/lary.24834
pubmed: 25045896
Egli Gallo D, Khojasteh E, Gloor M et al (2013) Effectiveness of systemic high-dose dexamethasone therapy for idiopathic sudden sensorineural hearing loss. Audiol Neurootol 18:161–170
doi: 10.1159/000346938
pubmed: 23446332
Equator-Network SPIRIT (2013) 2013 Statement: Defining standard protocol items for clinical trials. http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/ . Accessed 8 May 2022
Furuhashi A, Matsuda K, Asahi K et al (2002) Sudden deafness: long-term follow-up and recurrence. Clin Otolaryngol 27:458–463
doi: 10.1046/j.1365-2273.2002.00612.x
pubmed: 12472512
Garavello W, Galluzzi F, Gaini RM et al (2012) Intratympanic steroid treatment for sudden deafness: a meta-analysis of randomized controlled trials. Otol Neurotol 33:724–729
doi: 10.1097/MAO.0b013e318254ee04
pubmed: 22699982
Garcia-Berrocal JR, Ramirez-Camacho R, Lobo D et al (2008) Adverse effects of glucocorticoid therapy for inner ear disorders. ORL J Otorhinolaryngol Relat Spec 70:271–274
doi: 10.1159/000134381
pubmed: 18500172
Gurgel RK, Jackler RK, Dobie RA et al (2012) A new standardized format for reporting hearing outcome in clinical trials. Otolaryngol Head Neck Surg 147:803–807
doi: 10.1177/0194599812458401
pubmed: 22931898
Klemm E, Bepperling F, Burschka MA et al (2007) Hemodilution therapy with hydroxyethyl starch solution (130/0.4) in unilateral idiopathic sudden sensorineural hearing loss: a dose-finding, double-blind, placebo-controlled, international multicenter trial with 210 patients. Otol Neurotol 28:157–170
doi: 10.1097/01.mao.0000231502.54157.ad
pubmed: 17255882
Klemm E, Deutscher A, Mosges R (2009) A present investigation of the epidemiology in idiopathic sudden sensorineural hearing loss. Laryngorhinootologie 88:524–527
doi: 10.1055/s-0028-1128133
pubmed: 19194837
Labus J, Breil J, Stutzer H et al (2010) Meta-analysis for the effect of medical therapy vs. placebo on recovery of idiopathic sudden hearing loss. Laryngoscope 120:1863–1871
doi: 10.1002/lary.21011
pubmed: 20803741
Li H, Feng G, Wang H et al (2015) Intratympanic steroid therapy as a salvage treatment for sudden sensorineural hearing loss after failure of conventional therapy: a meta-analysis of randomized, controlled trials. Clin Ther 37:178–187
doi: 10.1016/j.clinthera.2014.11.009
pubmed: 25542075
Liu XX, Zhu XM, Miao Q et al (2014) Hyperglycemia induced by glucocorticoids in nondiabetic patients: a meta-analysis. Ann Nutr Metab 65:324–332
doi: 10.1159/000365892
pubmed: 25402408
Mebrahtu TF, Morgan AW, West RM et al (2020) Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study. CMAJ 192:E295–E301
doi: 10.1503/cmaj.191012
pubmed: 32392512
pmcid: 7101178
Merkofer F, Struja T, Delfs N et al (2022) Glucose control after glucocorticoid administration in hospitalized patients—a retrospective analysis. BMC Endocr Disord 22:8
doi: 10.1186/s12902-021-00914-3
pubmed: 34986826
pmcid: 8734262
Ng JH, Ho RC, Cheong CS et al (2015) Intratympanic steroids as a salvage treatment for sudden sensorineural hearing loss? A meta-analysis. Eur Arch Otorhinolaryngol 272:2777–2782
doi: 10.1007/s00405-014-3288-8
pubmed: 25217083
Niedermeyer HP, Zahneisen G, Luppa P et al (2003) Cortisol levels in the human perilymph after intravenous administration of prednisolone. Audiol Neurootol 8:316–321
doi: 10.1159/000073516
pubmed: 14566102
Nosrati-Zarenoe R, Hultcrantz E (2012) Corticosteroid treatment of idiopathic sudden sensorineural hearing loss: randomized triple-blind placebo-controlled trial. Otol Neurotol 33:523–531
doi: 10.1097/MAO.0b013e31824b78da
pubmed: 22429944
Olzowy B, Osterkorn D, Suckfull M (2005) The incidence of sudden hearing loss is greater than previously assumed. MMW Fortschr Med 147:37–38
pubmed: 15887682
Plontke S (2005) Therapy of hearing disorders—conservative procedures. GMS Curr Top Otorhinolaryngol Head Neck Surg 4:Doc1
pubmed: 22073049
pmcid: 3200997
Plontke SK, Bauer M, Meisner C (2007) Comparison of pure-tone audiometry analysis in sudden hearing loss studies: lack of agreement for different outcome measures. Otol Neurotol 28:753–763
doi: 10.1097/MAO.0b013e31811515ae
pubmed: 17948355
Plontke SK, Lowenheim H, Mertens J et al (2009) Randomized, double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy. Laryngoscope 119:359–369
doi: 10.1002/lary.20074
pubmed: 19172627
Rahne T, Buthut F, Plössl S et al (2016) A software tool for puretone audiometry. Classification of audiograms for inclusion of patients in clinical trials. HNO 64(Suppl 1):S1–S6
doi: 10.1007/s00106-015-0089-3
pubmed: 26607156
Rauch SD, Halpin CF, Antonelli PJ et al (2011) Oral vs intratympanic corticosteroid therapy for idiopathic sudden sensorineural hearing loss: a randomized trial. JAMA 305:2071–2079
doi: 10.1001/jama.2011.679
pubmed: 21610239
Rohrmeier C, Koemm N, Babilas P et al (2012) Sudden sensorineural hearing loss: systemic steroid therapy and the risk of glucocorticoid-induced hyperglycemia. Eur Arch Otorhinolaryngol 270(4):1255–1261
doi: 10.1007/s00405-012-2134-0
pubmed: 22843065
Sahin M, Kebapcilar L, Taslipinar A et al (2009) Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing’s syndrome in obese patients. Intern Med 48:33–39
doi: 10.2169/internalmedicine.48.1234
pubmed: 19122354
Schäcke H, Döcke WD, Asadullah K (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96:23–43
doi: 10.1016/S0163-7258(02)00297-8
pubmed: 12441176
Siegel LG (1975) The treatment of idiopathic sudden sensorineural hearing loss. Otolaryngol Clin North Am 8:467–473
doi: 10.1016/S0030-6665(20)32783-3
pubmed: 1153209
Sindhusake D, Mitchell P, Smith W et al (2001) Validation of self-reported hearing loss. The Blue Mountains Hearing Study. Int J Epidemiol 30:1371–1378
doi: 10.1093/ije/30.6.1371
pubmed: 11821349
Stachler RJ, Chandrasekhar SS, Archer SM et al (2012) Clinical practice guideline: sudden hearing loss. Otolaryngol Head Neck Surg 146:S1–S35
doi: 10.1177/0194599812436449
pubmed: 22383545
Van Raalte DH, Ouwens DM, Diamant M (2009) Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur J Clin Invest 39:81–93
doi: 10.1111/j.1365-2362.2008.02067.x
pubmed: 19200161
Wei BP, Stathopoulos D, O’Leary S (2013) Steroids for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev 7:Cd3998
Westerlaken BO, Stokroos RJ, Dhooge IJ et al (2003) Treatment of idiopathic sudden sensorineural hearing loss with antiviral therapy: a prospective, randomized, double-blind clinical trial. Ann Otol Rhinol Laryngol 112:993–1000
doi: 10.1177/000348940311201113
pubmed: 14653370
Whitworth JA (1992) Adrenocorticotrophin and steroid-induced hypertension in humans. Kidney Int Suppl 37:S34–S37
pubmed: 1321309
WHO (2021) Deafness and hearing loss. https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss . Accessed 8 May 2022
WHO (2017) Global costs of unaddressed hearing loss and cost-effectiveness of interventions: a WHO report. https://apps.who.int/iris/handle/10665/254659 . Accessed 8 May 2022
WHO (2021) World report on hearing. https://www.who.int/publications/i/item/world-report-on-hearing . Accessed 8 May 2022