Prophylactic nimodipine treatment for hearing preservation after vestibular schwannoma surgery: a randomized multi-center phase III trial (AkNiPro2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Martin-Luther-Universitaet Halle-Wittenberg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Jan 2021 → 10 Jun 2025

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

German Research Foundation (DFG)

External identifiers

EU CT number

2024-518182-10-00

EudraCT number

2019-002317-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Prophylaxis

To assess the efficacy and safety of prophylactic nimodipine treatment on hearing preservation after VS surgery in comparison to standard care only.

Secondary objectives 1

1. To compare the postoperative and late postoperative cochlear nerve function according to GR scale with preoperative function, change in PTA and WRSmax, compare GR-scores and AAOHNS-scores, intraoperative BAEP mean values, to investigate subjective quality of life, the anatomical preservation of the cochlear nerve and wave V and safety.

Conditions and MedDRA coding

Acoustic schwannoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male and female adults age ≥ 18 years
2. Vestibular schwannomas (Koos I-IV) with indication for surgery
3. Preoperative pure tone audiometry (not older than 3 months prior to surgery), hearing function according to Gardner-Robertson scale (GR) 1-3 (Air-conduction PTA<90 dB HL)
4. Preoperative MRI (not older than 6 months prior to surgery)
5. Written informed consent obtained according to international guidelines and local laws
6. Ability to understand and give informed consent
7. Safe contraception measures for males and females. Procedures with a pearl index of less than 1% or abstinence apply as safe pregnancy prevention measures

Exclusion criteria 13

1. Hearing function GR 4-5 (Air-conduction PTA (0.5-3kHz) >=90 dB HL)
2. Conductive hearing loss at affected side (mean air-bone gap (0.5, 1, 2, 3 kHz) >10 dB) if bone-conduction is measurable
3. Previously irradiated or surgical treated VS
4. Neurofibromatosis, other brain tumors, other reasons for inoperability
5. Pregnancy and lactation period
6. Known hypersensitivity to nimodipine or any of the excipients (ethanol, Macrogol, sodiumcitrate, citric acid) to be used for nimodipine infusion
7. History of (reformed alcoholic or) persistent abuse of alcohol
8. Known current kidney or liver insufficiency
9. Any medical condition that in the opinion of the investigator would not permit participation in the clinical trial.
10. Unstable angina pectoris and/or Myocardial infarction during the last four weeks before start of treatment
11. Severe, uncontrolled, symptomatic hypotension at inclusion
12. Subjects with psychological, psychiatric, neurological, familial, sociological, or geographical conditions that do not permit compliance with the protocol as well as officially and/or legally accomodated persons
13. Participation in another interventional trial simultaneously and within the last 30 days prior to inclusion (registries or observational studies allowed)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Postoperative cochlear nerve function measured before discharge according to GR scale 1-3 versus GR 4-5 (binary)

Secondary endpoints 9

1. Late postoperative cochlear nerve function measured at follow up three to six months after surgery (end of study) according to GR scale 1-3 versus GR 4-5 (binary)
2. Postoperative deterioration of cochlear nerve function of at least one grade according to the GR scale compared with its preoperative function (binary)
3. Late postoperative deterioration of cochlear nerve function of at least one grade according to the GR scale compared with its preoperative function measured at follow up three to six months after surgery (end of study) (binary)
4. Change of pure-tone thresholds (PTA) and speech discrimination score (WRSmax)
5. Comparison between GR-scores and AAOHNS-scores
6. Intraoperative deterioration of BAEP mean values (amplitudes and latencies)
7. Subjective quality of life / psychosocial impairment assessed by patient’s questionnaires (HHIE, SF-12, PANQOL) before surgery and at follow up three to six months
8. Anatomical preservation of the cochlear nerve and preservation of wave V (BAEP)
9. Data on the safety and side effects of the medication will be obtained. For this purpose, adverse events are recorded descriptively in both groups and evaluated. Particular attention will be paid to intra and postoperative symptomatic hypotension.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Martin-Luther-Universitaet Halle-Wittenberg

Sponsor organisation

Martin-Luther-Universitaet Halle-Wittenberg

Address

Ernst-Grube-Strasse 40, Kroellwitz Kroellwitz

City

Halle (Saale)

Postcode

06120

Country

Germany

Scientific contact point

Organisation

Martin-Luther-Universitaet Halle-Wittenberg

Contact name

Prof. Christian Scheller

Public contact point

Organisation

Martin-Luther-Universitaet Halle-Wittenberg

Contact name

Prof. Christian Scheller

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications