Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-003109-92
    Sponsor's Protocol Code Number:CRFSPN004
    National Competent Authority:Ireland - HPRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-10-02
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedIreland - HPRA
    A.2EudraCT number2019-003109-92
    A.3Full title of the trial
    Ketamine as an adjunctive therapy for Major Depression (2) - a randomised controlled trial
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to look at Ketamine as an additional treatment for people with depression
    A.3.2Name or abbreviated title of the trial where available
    KARMA-Dep (2)
    A.4.1Sponsor's protocol code numberCRFSPN004
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04939649
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorTrinity College Dublin
    B.1.3.4CountryIreland
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportHealth Research Board
    B.4.2CountryIreland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTrinity College Dublin
    B.5.2Functional name of contact pointQuality and regulatory Affairs mgr
    B.5.3 Address:
    B.5.3.1Street AddressResearch Contracts and Consultancy, Trinity Innovation & Enterprise, House 4, Trinity College Dublin
    B.5.3.2Town/ cityDublin 2
    B.5.3.3Post codeD02 PN40
    B.5.3.4CountryIreland
    B.5.6E-mailclinicaltrialsponsorship@tcd.ie
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Ketalar
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Healthcare Ireland
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNKetamine Hydrochloride
    D.3.9.3Other descriptive nameKETAMINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB02830MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Hypnovel
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Products (Ireland) Ltd
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMIDAZOLAM HYDROCHLORIDE
    D.3.9.1CAS number 59467-96-8
    D.3.9.4EV Substance CodeSUB03289MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Major Depression
    E.1.1.1Medical condition in easily understood language
    Depression
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Mental Disorders [F03]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To conduct a pragmatic randomised controlled patient- and rater-blinded trial of repeated adjunctive twice-weekly ketamine vs. midazolam infusions over up to four weeks for patients hospitalised for depression and assess the mood-rating score difference between arms from before the first infusion to 24 hours after the final infusion, supplemented by a 95% confidence interval. There will also be a 24-week follow-up after the final infusion session.
    E.2.2Secondary objectives of the trial
    1. To assess response and remission rates at the end of the randomised treatment phase and, relapse status after 24 weeks.

    2. To assess the safety and tolerability in inpatients with depression of repeated (up to 8) infusions of ketamine vs midazolam regarding psychotomimetic, other psychiatric, and cognitive side-effects.

    3. To assess the safety and tolerability in inpatients with depression of repeated (up to 8) infusions of ketamine vs midazolam regarding haemodynamic stability, neurological, urological, and other physical health side-effects.

    4. To conduct quality-of-life and cost-effectiveness analyses for patients participating in the KARMA-Dep (2) Trial.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Biomarker study
    E.3Principal inclusion criteria
    Participants may be male or female, aged ≥18 years, and from a variety of geographical (within Ireland) and socioeconomic backgrounds. To be eligible for inclusion, each participant must meet each of the following criteria at screening (Visit 0) and continue to fulfil these criteria at baseline before the first ketamine/midazolam infusion (Visit 1).

    1. Participants must be voluntary admissions and able and willing to give written informed consent and comply with the requirements of this study protocol.
    2. Admitted to hospital and diagnosed with major depressive disorder or bipolar disorder (current episode depression), confirmed by the Mini International Neuropsychiatric Interview (MINI); and have a Montgomery-Åsberg Rating Scale for Depression (MADRS) score ≥20 at screening and start of the first infusion.
    3. Female patients of child-bearing potential and male patients whose partner is of child-bearing potential must be willing to ensure that they or their partner use two contraception methods, including a barrier method, during the randomised treatment phase and for 12 weeks thereafter.
    4. Female patients' plasma pregnancy test performed at the screening visit must be negative.
    5. Patients have clinically acceptable laboratory and ECG findings during the current admission prior to the first infusion session.
    E.4Principal exclusion criteria
    Patients are excluded from the study if any of the following criteria are met at Screening (Visit 0) or at baseline before the first infusion session (Visit 1):

    1. Current involuntary admission
    2. Patients unable to provide written informed consent
    3. Patients who have participated in another ketamine study or received any other investigational agent within the past 12 months
    4. Medical condition rendering unfit for ketamine or midazolam (Ketamine is contraindicated, as per Summary of Product Characteristics, in persons in whom an elevation of blood pressure would constitute a serious hazard. Ketamine should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, C.V.A. or cerebral trauma or if there is hypersensitivity to the active substance. Contraindications to midazolam include known hypersensitivity to benzodiazepines, severe respiratory failure or acute respiratory depression. Bradycardia is a known adverse effect of midazolam and ketamine. Therefore, patients with pre-existing bradycardia will be excluded.)
    5. Currently taking any of the following medications which are contraindicated during the randomised treatment period as they may alter the pharmacokinetics of ketamine. Additionally, the medication theophylline is contraindicated as concomitant use of ketamine and theophylline may significantly reduce the seizure threshold with reports of unpredictable extensor-type seizures.

    Contraindicated medications:
    Ketoconazole
    Voriconazole
    Itraconazole
    Fluconazole
    Erythromycin
    Telithromycin
    Clarithromycin
    Saquinavir
    Nefazodone
    Diltiazem
    Verapamil
    Theophylline

    6. Active suicidal intention (score of 6 on item 10 (Suicidal Thoughts) in the MADRS)
    7. Confirmed diagnosis of dementia
    8. Lifetime history of schizophrenia or schizoaffective disorder; active anorexia nervosa or bulimia nervosa in the past 12 months; alcohol or other substance use disorder (with the exception of nicotine) in the previous six months; any DSM-5 disorder other than a major depressive episode (unipolar or bipolar) as the primary presenting problem
    9. ECT administered within the last two months
    10. Pregnancy or inability to confirm use of adequate contraception during the trial
    11. Breastfeeding women
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome is the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS). Response to treatment is defined as a ≥50% improvement from baseline MADRS score.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary outcome is the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score 24 hours after the final infusion.

    MADRS will be completed at screening (prior to randomisation), before and after all infusion sessions (at the following timepoints: -40 (±20) mins before the infusion begins; +60 (±10) mins and +120 (±10) mins after the infusion begins; +24 (±1) hours after the infusion ends) and at the 6, 12 and 24 weeks follow-up time points.
    E.5.2Secondary end point(s)
    Secondary safety and tolerability outcomes consist of psychotomimetic, dissociative, cognitive and physical health effects of repeated ketamine infusions, measured before, during and after infusions using a range of validated instruments.
    Psychotomimetic and dissociative symptoms, Cognitive effects, Physical safety and tolerability, Withdrawal effects highlighted in the protocol are being used to collect information as safety endpoints related to the IMPs. These will be exempted from reporting in the eCRF as adverse events. However, if they come to fulfil the SAE criteria they will be reported to pharmacovigilance as such.

    Treatment costs will be collected and other healthcare costs estimated using a version the Client Service Receipt Inventory (CSRI) adapted for a recent antidepressant trial and cost-effectiveness study. Health-related quality-of-life will be measured using the EQ-5D-5L (Five-level version of the EuroQol five-dimensional questionnaire).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety and tolerability assessments will be completed at screening (prior to randomisation), after all infusion sessions (+120 (±10) mins after the infusion begins), and at the 6, 12 and 24 weeks follow-up time points.

    Healthcare cost assessments and quality of life assessments will be completed at screening, week 6, week 12 and week 24.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Rater and patient blinded, pragmatic, randomised, controlled, parallel-group, superiority trial.
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 78
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 26
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state104
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-11-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-20
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon May 06 08:39:42 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA