Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
90
Countries
1
Sites
15
refractory chronic cluster headache
Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo)
Key facts
- Sponsor
- University Hospital Of Clermont-Ferrand
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
- Trial duration
- 15 Sep 2021 → 23 Dec 2025
- Decision date (initial)
- 2024-12-03
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- CHU de Clermont-Ferrand
External identifiers
- EU CT number
- 2024-518943-38-00
- EudraCT number
- 2020-003604-14
- ClinicalTrials.gov
- NCT04814381
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo)
Secondary objectives 4
- Evaluate the effect of an infusion of a combination of ketamine and magnesium sulfate in patients suffering from chronic cluster headache, compared to a non-analgesic anxiolytic treatment, on anxiety and depression
- Evaluate the tolerance of an infusion of a combination of ketamine and magnesium sulfate in patients suffering from chronic cluster headache, compared to a non-analgesic anxiolytic treatment
- Evaluate the intensity of crises
- Evaluate the effect of an infusion of a combination of ketamine and magnesium sulfate in patients suffering from chronic cluster headache, compared to a non-analgesic anxiolytic treatment, on management costs
Conditions and MedDRA coding
refractory chronic cluster headache
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Allocation du traitement Les patients seront randomisés en 2 groupes :
- Traitement actif : kétamine 0,5mg/kg administrée sur 2 heures par voie IV dans 50cc de
NaCl, plus 3g de sulfate de magnésium dans 250 ml de NaCl sur 30 minutes
- Traitement anxiolytique non antalgique : hydroxyzine 25mg administrée sur 2 heures par
voie IV dans 50cc de NaCl, plus 250 ml de NaCl sur 30 minutes
La randomisation sera effectuée de façon centralisée via l’utilisation de Ennov Clinical. Elle sera
stratifiée en fonction du sexe et du centre.
|
Randomised Controlled | Double | [{"id":157532,"code":3,"name":"Monitor"},{"id":157534,"code":1,"name":"Subject"},{"id":157533,"code":2,"name":"Investigator"}] | Traitement actif: kétamine 0,5mg/kg administrée sur 2 heures par voie IV dans 50cc de NaCl, plus 3g de sulfate de magnésium dans 250 ml de NaCl sur 30 minutes Traitement anxiolytique non antalgique: hydroxyzine 25mg administrée sur 2 heures par voie IV dans 50cc de NaCl, plus 250 ml de NaCl sur 30 minutes |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Age ≥ 18 years
- Diagnosis of chronic cluster headache according to ICHD-3 criteria
- Presence of at least 2 crises/24 hours on average during the 14 days preceding the ketamine infusion
- Insufficient effectiveness, intolerance or contraindication to the use of the 3 major treatments for the management of cluster headaches: verapamil, lithium and corticosteroids (oral or suboccipital injections)
- informed consent
Exclusion criteria 9
- Pregnant or breastfeeding woman
- Contraindication to the use of ketamine
- Use of ketamine in the year preceding the study
- Severe renal failure
- Severe liver failure
- Implementation or modification of an analgesic treatment (background treatments) in the 7 days preceding the infusion
- Patient under legal protection measure
- Addictive behaviors
- Corrected QT > 450ms
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change in weekly frequency of crisis over the period D7-D13 compared to the pre-treatment period
Secondary endpoints 11
- Change in weekly frequency of crisis over the period D14-D20, D21-D27, D28-D34 compared to the pre-treatment period
- The proportion of responders at 30%, 50% and 75% each week post-infusion
- Response to treatment according to initial serum magnesium
- The weekly frequency and intensity of crisis between the 7 days preceding the infusion and each week post infusion
- Crisis treatments intake
- Anxiety and depression scoring (HAD)
- The PGIC scoring for the overall clinical evaluation on D15 and D90
- The proportion of patients requiring additional treatment on D15
- Direct medical costs
- Evaluation of adverse effects
- Evaluation of blinding quality
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SULFATE DE MAGNESIUM LAVOISIER 15 POUR CENT (0,15 g/ml), solution injectable (I.V.) en ampoule
PRD494315 · Product
- Active substance
- Magnesium Sulfate Heptahydrate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 3 g gram(s)
- Max total dose
- 6 g gram(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- B05XA05 — MAGNESIUM SULFATE
- Marketing authorisation
- 34009 362 998 0 1
- MA holder
- LABORATOIRES CHAIX ET DU MARAIS
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
KETAMINE RENAUDIN 50 mg/ml, solution injectable
PRD2927934 · Product
- Active substance
- Ketamine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 0.5 mg/Kg milligram(s)/kilogram
- Max total dose
- 1 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- N01AX03 — KETAMINE
- Marketing authorisation
- 34009 578 540 2 7
- MA holder
- LABORATOIRE RENAUDIN
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
HYDROXYZINE RENAUDIN 100 mg/2 mL, solution injectable
PRD2902926 · Product
- Active substance
- Hydroxyzine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- N05BB01 — HYDROXYZINE
- Marketing authorisation
- 34009 361 356 5 9
- MA holder
- LABORATOIRE RENAUDIN
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 1
CHLORURE DE SODIUM 0,9 % BAXTER, solution pour perfusion en poche
PRD367014 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 300 ml millilitre(s)
- Max total dose
- 600 ml millilitre(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- B05XA03 — SODIUM CHLORIDE
- Marketing authorisation
- 34009 351 878 9 5
- MA holder
- BAXTER SAS
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
University Hospital Of Clermont-Ferrand
- Sponsor organisation
- University Hospital Of Clermont-Ferrand
- Address
- 58 Rue Montalembert
- City
- Clermont Ferrand Cedex 1
- Postcode
- 63003
- Country
- France
Scientific contact point
- Organisation
- University Hospital Of Clermont-Ferrand
- Contact name
- Lise Laclautre
Public contact point
- Organisation
- University Hospital Of Clermont-Ferrand
- Contact name
- Lise Laclautre
Locations
1 EU/EEA country · 15 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 90 | 15 |
| Rest of world | — | 0 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
Centre Urgences Céphalées, 2 Rue Ambroise Pare, 75475, Paris Cedex 10
Clinique Beau Soleil
Neurologie, 119 avenue de Lodève, 34070, Montpellier
Centre Hospitalier Universitaire Rouen
Neurologie, 1 Rue De Germont, 76000, Rouen
Hospices Civils De Lyon
neurologie fonctionnelle et épileptologie, 59 Boulevard Pinel, 69500, Bron
Centre Hospitalier Universitaire De Toulouse
Neurologie, 2 Rue Viguerie, Tsa 80035, Toulouse
Centre Hospitalier Universitaire De Nantes
Neurologie, Boulevard Du Professeur Jacques Monod, 44800, Saint Herblain
Centre Hospitalier Universitaire Grenoble Alpes
Neurologie, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Centre Hospitalier Universitaire De Montpellier
Neurologie, 191 Avenue Du Doyen Gaston Giraud, 34295, Montpellier Cedex 5
University Hospital Of Clermont-Ferrand
Neurologie, 58 Rue Montalembert, 63003, Clermont Ferrand Cedex 1
Centre Hospitalier Regional De Marseille
Centre d’évaluation et de traitement de la douleur, 264 Rue Saint Pierre, 13005, Marseille
University Hospital Of Clermont-Ferrand
Neurologie, 58 Rue Montalembert, 63000, Clermont-Ferrand
Centre Hospitalier Universitaire De Lille
Centre d’évaluation et de traitement de la douleur, 2 Avenue Oscar Lambret, Cs 70001, Lille Cedex
Centre Hospitalier Universitaire De Saint Etienne
Centre de la Douleur, Avenue Albert Raimond, 42270, Saint Priest En Jarez
Polyclinique Jean Villar
Neurologie, 56 avenue Maryse Bastie, 33520, BRUGES
Les Hopitaux Universitaires De Strasbourg
Centre d’évaluation et de traitement de la douleur, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
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 |
|---|---|---|---|---|---|
| France | 2021-09-15 | 2025-12-23 | 2021-09-15 | 2025-10-16 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | 2024-518943-38-00_Tableau comparatif-MS6_20251001_KETALGIA | 1 |
| Protocol (for publication) | D1_Protocol signature_2024-518943-38-00 | 10 |
| Protocol (for publication) | D1_Protocol_2024-518943-38-00 | 10 |
| Protocol (for publication) | D1_Protocol_2024-518943-38-00_modifications apparentes | 10 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_2024-518943-38-00 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF patient | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | G1_SmPC_Hydroxyzine | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G1_SmPC_Ketamine | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G1_SmPC_sulfate de magnesium | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_FR_2024-518943-38-00 | 8.1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-18 | France | Acceptable 2024-11-28
|
2024-12-03 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-02-03 | France | Acceptable 2025-02-20
|
2025-02-26 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-11-04 | France | Acceptable 2025-12-12
|
2025-12-17 |