AmaNtadine for NeuroenhancEment in acutE patients Study - A prospective pilot proof of concept phase IIb study in intensive and intermediate care unit patients (ANNES)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Mar 2023 → 4 Dec 2025

Decision date (initial)

2024-03-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512333-33-00

EudraCT number

2022-002418-18

ClinicalTrials.gov

NCT05479032

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate that Amantadine is efficacious in
increasing the level of vigilance/responsiveness as
measured by clinical scores, mainly the Glasgow Coma
Scale (GCS). The primary outcome is the measure of
the level of vigilance by GCS after 120 hrs (± 4hrs.), i.e.
5 days, of treatment

Secondary objectives 1

1. The secondary objective is Improvement of vigilance measured via alternative scales(Richmond Agitation-Sedation Scale (RASS), Full Outline of UnResponsiveness(FOUR) Score Coma Scale), Intensive Care Delirium Screening Checklist (ICDSC),National Institute of health Stroke Scale (NIHSS), modified Rankin Scale (mRS),Glasgow Outcome Scale – Extended (GOS-E), Coma Recovery Scale revised (CRSR)and Montreal Cognitive Assessment (MoCA) after 90 days, EEG results, survivaland clinical improvement reported within the therapists’ questionnaire.

Conditions and MedDRA coding

unresponsive wakefulness syndrome not otherwise explained

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. consent. Informed consent:o The patient understands the study proceduresand voluntarily signs an informed consentdocumentoro If a subject has per definition reducedconsciousness and therefore is not in a positionto provide written informed consent, prior to anystudy related assessments/procedures thepatient’s legal representative can give writteninformed consent. Females: pregnancy excluded by measurement ofhuman chorionic gonadotropin (hCG) in serum beforestart of study medication (in woman of child bearingpotential) Reduced consciousness, lasting at least 72 h, definedas GCS <8, not otherwise explained Inconspicuous EEG and ECG

Exclusion criteria 1

1. Women during pregnancy and lactation. History of hypersensitivity to the investigationalmedicinal product or to any drug with similar chemicalstructure or to any excipient present in thepharmaceutical form of the investigational medicinalproduct. Participation in other interventional study.(Participation in an observational trial is acceptable.) Reduced consciousness, otherwise sufficientlyexplained, such as reduced consciousness due tostatus epilepticus, hyperglycaemia, electrolyteimbalance, hyperkalaemia, akinetic crisis inParkinson’s disease) Delirium (Intensive CareDelirium Screening Checklist (ICDSC) > 4 or >5 inaphasic patients) History of epileptic seizures or status epilepticus Concomitant therapy with memantine Severe uncompensatedheart failure (NYHA IV) cardiomyopathy and myocarditis Atriventricular block (AV block) second-degree andthird-degree known bradykcardia (below 55 beats/minute) Known long QT interval (QTc according to Bazett > 420ms) or recognizable U-waves or congenital QTsyndrome in the Family history a history of serious ventricular arrhythmias, includingtorsade de pointes hypokalemia or hypomagnesemia concomitant therapy with Budipin or other QTprolongingdrugs impaired renal function, measured by glomerularfiltration rate (GFR) < 10 ml/min

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A patient will bedefined as a responder if he/she improves by at least 3 points on the GCS after 5 days oftreatment at study visit 6

Secondary endpoints 1

1. The secondary objective is Improvement of vigilance measured via alternative scales(Richmond Agitation-Sedation Scale (RASS), Full Outline of UnResponsiveness(FOUR) Score Coma Scale), Intensive Care Delirium Screening Checklist (ICDSC),National Institute of health Stroke Scale (NIHSS), modified Rankin Scale (mRS),Glasgow Outcome Scale – Extended (GOS-E), Coma Recovery Scale revised (CRSR)and Montreal Cognitive Assessment (MoCA) after 90 days, EEG results, survivaland clinical improvement r

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Manola Zago

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Manola Zago

Locations

1 EU/EEA country · 1 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 7 files

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

Application history

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