Methylphenidate for Early Awakening in Coma (MEAWAKE)

2025-524937-19-00 Protocol MEAWAKE_1 Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 4 EU/EEA countries · 5 sites · Protocol MEAWAKE_1

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 324
Countries 4
Sites 5

Coma due to acute brain injury

This is an international, prospective, randomized, placebo-controlled, double-blind clinical trial to determine whether daily methylphenidate administration leads to earlier awakening in coma patients with acute brain injury compared to placebo.

Key facts

Sponsor
Rigshospitalet
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Decision date (initial)
2026-04-30
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Lundbeck Foundation (R507-2025-286)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

This is an international, prospective, randomized, placebo-controlled, double-blind clinical trial to determine whether daily methylphenidate administration leads to earlier awakening in coma patients with acute brain injury compared to placebo.

Secondary objectives 3

  1. To investigate if covert consciousness (detected via pupillometry, NIRS or fMRI) predicts drug response.
  2. To examine EEG connectivity changes associated with awakening and methylphenidate administration.
  3. To assess safety and feasibility of repeated methylphenidate administration in ICU patients.

Conditions and MedDRA coding

Coma due to acute brain injury

VersionLevelCodeTermSystem organ class
20.0 PT 10010071 Coma 100000004852

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Adults (≥18 years) admitted to the intensive care unit (ICU) with acute traumatic or non-traumatic brain injury
  2. Unresponsiveness (FOUR score ≤11, or SECONDs ≤5); no signs of consistent command-following
  3. Hemodynamically stable
  4. Informed consent from legal proxy

Exclusion criteria 4

  1. Preexisting severe mental handicap
  2. Active seizures or status epilepticus
  3. Anticipated withdrawal of life-sustaining therapy or death within 48h
  4. Hepatic or renal failure (as judged by investigator)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Time to awakening, defined as first sustained improvement in consciousness (FOUR, e = 4; or FOUR, total score ≥12; or SECONDs ≥6; confirmed on two consecutive exams 1h apart).

Secondary endpoints 3

  1. Proportion of patients achieving clinical arousal
  2. ICU mortality and length of stay
  3. 3-month outcome (mRS, CPC, GOS-E)

Investigational products

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

Test 1

Methylphenidate Hydrochloride

SCP102633598 · ATC

Active substance
Methylphenidate Hydrochloride
Substance synonyms
METHYLPHENIDYLACETATE HYDROCHLORIDE, SPD-544
Route of administration
ORAL
Max daily dose
20 mg milligram(s)
Max total dose
200 mg milligram(s)
Max treatment duration
10 Week(s)
Authorisation status
Authorised
ATC code
N06BA04 — METHYLPHENIDATE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo manufactured by the hospital pharmacy of the Capital Region in Denmark; The placebo product does not contain active substance and is otherwise identical to the IMP after preparation.

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

94 Total trials 54 Recruiting 24 Ended
Academic / Non-commercial
Sponsor organisation
Rigshospitalet
Address
Blegdamsvej 9
City
Copenhagen Oe
Postcode
2100
Country
Denmark

Scientific contact point

Organisation
Rigshospitalet
Contact name
Daniel Kondziella

Public contact point

Organisation
Rigshospitalet
Contact name
Daniel Kondziella

Third parties 1

OrganisationCity, countryDuties
GCP-enheden ved Københavns Universitetshospital
ORL-000011207
 Frederiksberg, Denmark On site monitoring

Locations

4 EU/EEA countries · 5 investigational sites

By country

CountryMS statusPlanned subjectsSites
Austria Authorised, recruitment pending 65 1
Denmark Authorised, recruitment pending 129 2
France Authorised, recruitment pending 65 1
Germany Authorised, recruitment pending 65 1
Rest of world — 0 —

Investigational sites

Austria

1 site · Authorised, recruitment pending
Johannes Kepler University Linz
Department of Neurology, Wagner Jauregg Weg 15, 4020, Linz

Denmark

2 sites · Authorised, recruitment pending
Bispebjerg Hospital
Afdeling Z, Bispebjerg Hospital, IC-Forskning, Copenhagen
Rigshospitalet
Afdeling for Hjerne- og Nervesygdomme, Blegdamsvej 9, 2100, Copenhagen Oe

France

1 site · Authorised, recruitment pending
Hopitaux Universitaires Pitie Salpetriere
Department of Neurology, 47 Boulevard De L Hopital, 75651, Paris Cedex 13

Germany

1 site · Authorised, recruitment pending
Ludwig-Maximilians-Universitaet Muenchen
Department of Neurology, Marchioninistrasse 54, 81377, Munich

Results and documents

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

Documents 38 files

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

TypeTitleVersion
Protocol (for publication) D1_MEAWAKE_Protocol 1.2
Protocol (for publication) D1_MEAWAKE_Protocol_track changes 1.2
Recruitment arrangements (for publication) document_additionnel_ctr1 1
Recruitment arrangements (for publication) Documents-attendus-en-France-concernant-la-partie-II-de-CTA_2022_02_02 1
Recruitment arrangements (for publication) informedconsent_patientrecruitmentprocedure 1
Recruitment arrangements (for publication) informedconsent_patientrecruitmentprocedure_Munich 1
Recruitment arrangements (for publication) informedconsent_patientrecruitmentprocedure_Paris 1
Recruitment arrangements (for publication) informedconsent_patientrecruitmentprocedure_track changes 1
Recruitment arrangements (for publication) K1_informedconsent_patientrecruitmentprocedure_Linz 1
Recruitment arrangements (for publication) Part 2_Paris 1
Subject information and informed consent form (for publication) appendiks_methylphenidat_bivirkninger 1
Subject information and informed consent form (for publication) Deltagerinformation Paarrende_clean copy 1
Subject information and informed consent form (for publication) Deltagerinformation Paarrende_track changes 1
Subject information and informed consent form (for publication) Deltagerinformation Patient_clean copy 1
Subject information and informed consent form (for publication) Deltagerinformation Patient_track changes 1
Subject information and informed consent form (for publication) Deltagerinformation Trial gardian_clean copy 1
Subject information and informed consent form (for publication) Deltagerinformation Trial gardian_track changes 1
Subject information and informed consent form (for publication) Dine rettigheder som forsgsperson i forsg med medicin 1
Subject information and informed consent form (for publication) L1_Studieninfo und Aufklarung Gesetzlicher Vertreter_Linz 1
Subject information and informed consent form (for publication) L1_Studieninfo und Aufklarung Gesetzlicher Vertreter_Linz_track changes 1
Subject information and informed consent form (for publication) L2_Studieninfo und Aufklarung Patient Nachtraglich_Linz 1
Subject information and informed consent form (for publication) L2_Studieninfo und Aufklarung Patient Nachtraglich_Linz_track changes 1
Subject information and informed consent form (for publication) MEAWAKE_NIFC_poursuite_majeur_Paris 1
Subject information and informed consent form (for publication) MEAWAKE_NIFC_poursuite_majeur_Paris_track changes 1
Subject information and informed consent form (for publication) MEAWAKE_NIFC_proche_majeur_Paris 1
Subject information and informed consent form (for publication) MEAWAKE_NIFC_proche_majeur_Paris_track changes 1
Subject information and informed consent form (for publication) paaroerende-og-forsoegsvaerge-uafhaengig-laege 1
Subject information and informed consent form (for publication) Samtykkeerklring_Patient 1
Subject information and informed consent form (for publication) Studieninfo und Aufklarung Gesetzlicher Vertreter_Munich 1
Subject information and informed consent form (for publication) Studieninfo und Aufklarung Gesetzlicher Vertreter_Munich_track changes 1
Subject information and informed consent form (for publication) Studieninfo und Aufklarung Patient Nachtraglich_Munich 1
Subject information and informed consent form (for publication) Studieninfo und Aufklarung Patient Nachtraglich_Munich_track changes 1
Summary of Product Characteristics (SmPC) (for publication) F1_Motiron SmPC English 1
Synopsis of the protocol (for publication) D_Protocol synopsis_track changes 1
Synopsis of the protocol (for publication) D1_Protocol synopsis 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_French 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_French_track changes 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_German 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-12-17 Denmark Acceptable
2026-04-27
 2026-04-27