Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
148
Countries
1
Sites
6
Menière's disease
To determine whether intratympanic injection with 62.5 mg/ml methylprednisolon is superior to placebo in reducing the frequency of vertigo attacks in patients diagnosed with unilateral Meniere's disease during one year of follow-up.
Key facts
- Sponsor
- Leiden University Medical Center
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Otorhinolaryngologic Diseases [C09]
- Trial duration
- 5 Oct 2023 → ongoing
- Decision date (initial)
- 2023-05-23
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- ZonMw
External identifiers
- EU CT number
- 2023-503340-13-00
- ClinicalTrials.gov
- NCT05851508
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy
To determine whether intratympanic injection with 62.5 mg/ml methylprednisolon is superior to placebo in reducing the frequency of vertigo attacks in patients diagnosed with unilateral Meniere's disease during one year of follow-up.
Secondary objectives 7
- To determine whether methylprednisolone (62.5 mg/ml) compared to placebo has a superior effect on the use of escape medication and co-interventions.
- To determine whether methylprednisolone (62.5 mg/ml) compared to placebo has a superior effect on hearing.
- To determine whether methylprednisolone (62.5 mg/ml) compared to placebo has a superior effect on dizziness related quality of life.
- To determine whether methylprednisolone (62.5 mg/ml) compared to placebo has a superior effect on change in quality of life in tinnitus.
- To determine whether methylprednisolone (62.5 mg/ml) compared to placebo has a superior effect on change on general quality of life.
- To determine whether methylprednisolone (62.5 mg/ml) compared to placebo has a superior effect on adverse events.
- To determine whether methylprednisolone (62.5 mg/ml) compared to placebo has a superior effect on incremental cost difference.
Conditions and MedDRA coding
Menière's disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10058689 | Burning sensation in ears | 10013993 |
| 20.0 | LLT | 10063454 | Tympanic membrane injection | 10013993 |
| 20.0 | LLT | 10027185 | Meniere's syndrome | 10013993 |
| 20.0 | PT | 10047340 | Vertigo | 100000004854 |
| 20.1 | LLT | 10019246 | Hearing loss | 10013993 |
| 20.0 | PT | 10045210 | Tympanic membrane perforation | 100000004854 |
| 20.0 | LLT | 10058708 | Rotatory vertigo | 10013993 |
| 20.0 | PT | 10013573 | Dizziness | 100000004852 |
| 20.0 | SOC | 10013993 | Ear and labyrinth disorders | 10 |
| 20.0 | LLT | 10047339 | Vertiginous syndromes and other disorders of vestibular system | 10013993 |
| 20.0 | PT | 10043882 | Tinnitus | 100000004854 |
| 20.0 | HLT | 10023566 | Inner ear disorders NEC | 10013993 |
| 20.0 | PT | 10047386 | Vestibular disorder | 100000004854 |
| 20.1 | PT | 10049934 | Endolymphatic hydrops | 100000004854 |
| 20.0 | PT | 10033078 | Otitis media | 100000004862 |
| 20.0 | LLT | 10059614 | Vestibular vertigo | 10013993 |
| 20.0 | PT | 10022086 | Injection site pain | 100000004867 |
| 21.1 | LLT | 10081113 | Otitis media with effusion | 10021881 |
| 20.0 | PT | 10027183 | Meniere's disease | 100000004854 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Unilateral, definite MD according to the diagnostic criteria derived from the American Academy Otolaryngology Head and Neck Surgery, Classification Committee of the Bárány Society, European Academy of Otology and Neurotology and International Classification of Vestibular Disorders published in 2015.
- Age > 18 years at the start of the trial.
- ≥ 4 vertigo attacks over the last 6 months.
Exclusion criteria 7
- Bilateral Meniere's Disease.
- Severe disability (e.g. neurological, orthopaedic, cardiovascular) or serious concurrent illness that might interfere with treatment or follow-up.
- Active additional neuro-otologic disorders that may mimic MD (e.g. vestibular migraine, recurrent vestibulopathy, phobic postural vertigo, vertebro-basilar TIAs, acoustic neuroma).
- Otitis media with effusion based on tympanogram results.
- History of intratympanic injections with corticosteroid less than 6 months ago.
- History of intratympanic injections with gentamicin or ear surgery for treating MD.
- Women of child bearing age not using contraception, pregnant women, nursing women.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Complete or substantial control of vertigo (Class A or B).
Secondary endpoints 9
- Frequency of intratympanic injections with either gentamicin or corticosteroid (methylprednisolone, dexamethasone, triamcinolone)
- Pure tone audiometry
- Quality of life determined by the EQ-5D-5L questionnaire (EQ-5D and EQ-VAS scores)
- Dizziness related quality of life as determined by the DHI and FLS questionnaires
- Tinnitus related quality of life as determined by the TFI questionnaires
- (Serious) Adverse events
- SUSARs
- Cost effectiveness and cost-utility
- Frequency of use of metoclopramide
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Solu-Medrol 62,5 mg/ml, poeder en oplosmiddel voor oplossing voor injectie
PRD495323 · Product
- Active substance
- Methylprednisolone
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRATYMPANIC
- Max daily dose
- 62.5 mg/ml milligram(s)/millilitre
- Max total dose
- 62.5 mg milligram(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB04 — METHYLPREDNISOLONE
- Marketing authorisation
- RVG 07041
- MA holder
- PFIZER B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Natriumchloride 0,9 %, oplossing voor injectie
PRD567861 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRATYMPANIC
- Max daily dose
- 0.9 % (W/V) percent weight/volume
- Max total dose
- 0.9 % (W/V) percent weight/volume
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- B05XA03 — SODIUM CHLORIDE
- Marketing authorisation
- RVG 55227
- MA holder
- B.BRAUN MELSUNGEN AG
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 4
Dexamethason CF 20 mg/ml, injectievloeistof
PRD502494 · Product
- Active substance
- Dexamethasone
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRATYMPANIC
- Max daily dose
- 20 mg/ml milligram(s)/millilitre
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB02 — DEXAMETHASONE
- Marketing authorisation
- RVG 55091
- MA holder
- CENTRAFARM B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRIMPERAN 10 mg, suppositoire sécable
PRD518008 · Product
- Active substance
- Metoclopramide
- Pharmaceutical form
- SUPPOSITORY
- Route of administration
- RECTAL USE
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- A03FA01 — METOCLOPRAMIDE
- Marketing authorisation
- 34009 316 953 8 7
- MA holder
- SANOFI-AVENTIS FRANCE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Kenacort-A 40, suspensie voor injectie 40 mg/ml
PRD338432 · Product
- Active substance
- Triamcinolone Acetonide
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- INTRATYMPANIC
- Max daily dose
- 40 mg/ml milligram(s)/millilitre
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB08 — TRIAMCINOLONE
- Marketing authorisation
- RVG 05341
- MA holder
- BRISTOL-MYERS SQUIBB B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Gentamicine CF 40 mg/ml, injectievloeistof
PRD515746 · Product
- Active substance
- Gentamicin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRATYMPANIC
- Max daily dose
- 40 mg/ml milligram(s)/millilitre
- Max total dose
- 40 mg/ml milligram(s)/millilitre
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01GB03 — GENTAMICIN
- Marketing authorisation
- RVG 57572
- MA holder
- CENTRAFARM B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Leiden University Medical Center
- Sponsor organisation
- Leiden University Medical Center
- Address
- Albinusdreef 2
- City
- Leiden
- Postcode
- 2333 ZA
- Country
- Netherlands
Scientific contact point
- Organisation
- Leiden University Medical Center
- Contact name
- B.F. van Esch (principal investigator)
Public contact point
- Organisation
- Leiden University Medical Center
- Contact name
- B.F. van Esch (principal investigator)
Locations
1 EU/EEA country · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 148 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
Medisch Spectrum Twente
Otorhinolaryngology, Koningsplein 1, 7512 KZ, Enschede
Stichting Sint Franciscus Vlietland Groep
Otorhinolaryngology, Kleiweg 500, 3045 PM, Rotterdam
University Hospital Maastricht
Otorhinolaryngology and head and neck surgery, P Debyelaan 25, 6229 HX, Maastricht
Leiden University Medical Center
Otorhinolaryngology and head and neck surgery, Albinusdreef 2, 2333 ZA, Leiden
Gelre Hospitals
Otorhinolaryngology, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn
Haga Hospital
Otorhinolaryngology, Els Borst-Eilersplein 275, 2545 AA, 's-Gravenhage
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2023-10-05 | 2023-10-10 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-503340-13-00 | 6 |
| Protocol (for publication) | D4_Patient facing documents_DHI questionnaire | 1 |
| Protocol (for publication) | D4_Patient facing documents_EQ-5D-5L questionnaire | 1 |
| Protocol (for publication) | D4_Patient facing documents_FLS questionnaire | 1 |
| Protocol (for publication) | D4_Patient facing documents_iMCQ and iPCQ questionnaires | 1 |
| Protocol (for publication) | D4_Patient facing documents_TFI questionnaire | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_redacted | 3.1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Information Poster and Flyer | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Methylprednisolone sodium succinate_Solu-Medrol in Act-O-Vial_NL | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ENG 2023-503340-13-00 | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NL 2023-503340-13-00 | 3 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-06 | Netherlands | Acceptable with conditions 2023-05-22
|
2023-05-23 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-10-30 | Netherlands | Acceptable 2023-11-30
|
2023-11-30 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-08-12 | Netherlands | Acceptable 2024-11-11
|
2024-11-18 |