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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003604-14 | EudraCT Number |
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| Name | Class |
|---|---|
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
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Chronic cluster headache (CCH) is a rare primary headache disorder, defined by episodic attacks that occur for more than one year with no remission period or with remission periods lasting < 3 months (ICHD-3 criteria). In certain cases, CCH patients become drug-resistant and continue to suffer almost daily attacks.
Ketamine appears to be effective in a variety of chronic pain conditions, such as refractory headache, and can show an enhanced analgesic effect when combined with magnesium. A single infusion of ketamine-magnesium combination has been described to reduce attacks in 17 patients with rCCH. The main outcome was a comparison of the number of daily attacks two weeks prior to the infusion and one week after (days 7-8). The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (p<0.001). 13/17 had at least 50% response. Thus, the goal of this placebo-controlled study is to try to confirm these findings.
Chronic cluster headache (CCH) is a rare primary headache disorder, defined by episodic attacks that occur for more than one year with no remission period or with remission periods lasting < 3 months (ICHD-3 criteria). In certain cases, CCH patients become drug-resistant and continue to suffer almost daily attacks.
Ketamine appears to be effective in a variety of chronic pain conditions, such as refractory headache, and can show an enhanced analgesic effect when combined with magnesium. A single infusion of ketamine-magnesium combination has been described to reduce attacks in 17 patients with rCCH. The main outcome was a comparison of the number of daily attacks two weeks prior to the infusion and one week after (days 7-8). The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (p<0.001). 13/17 had at least 50% response. Thus, the goal of this placebo-controlled study is to try to confirm these findings.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine + Magnesium | Experimental | patients in the experimental group will receive 0.5mg/kg of ketamine over 2 hours, diluted in 50cc of NaCl 0.9% and 3g of magnesium sulfate over 30 minutes diluted in 250cc of NaCl 0.9%. |
|
| Control | Active Comparator | patients in the control group will receive 25mg of hydroxyzine over 2 hours, diluted in 50cc of NaCl 0.9% and 250cc of NaCl 0.9% over 30 minutes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine + Magnesium sulfate (drug combination) | Drug | A single infusion will be performed over 2 hours with 90 days follow-up. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in weekly attacks between day 7 - day 13 period compared to the pre-treatment period | Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 7 and day 13 period and pre-treatment period | pre-treatment period and day 7-day 13 post-treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of 30% responders | proportion of 30% responders at various time points according to the attack diary | day 7 to day 90 |
| Proportion of 50% responders | proportion of 50% responders at various time points according to the attack diary |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xavier MOISSET | University Hospital, Clermont-Ferrand | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CH Annecy Genevois | Annecy | 74370 | France | |||
| Polyclinique Jean Villar |
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| ID | Term |
|---|---|
| D003027 | Cluster Headache |
| ID | Term |
|---|---|
| D051303 | Trigeminal Autonomic Cephalalgias |
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D008278 | Magnesium Sulfate |
| D004338 | Drug Combinations |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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patients will be randomised with 1:1 ratio
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infusion will be prepared by a nurse that is not blinded to the treatment and will not take part to patient evaluation. Active and control treatments are of transparent colour and will not be recognisable.
| day 7 to day 90 |
| Proportion of 75% responders | proportion of 75% responders at various time points according to the attack diary | day 7 to day 90 |
| week by week attacks frequency | Area under the curve (AUC) for daily attacks evaluated each week between D0 and D90 (attacks diary) | day 0 to day 90 |
| patient global impression of change (PGIC) | PGIC will be completed and compared between the 2 groups | Day 15 |
| patient global impression of change (PGIC) | PGIC will be completed and compared between the 2 groups | Day 90 |
| Infusion's safety | proportion of patients in each group reporting any side effect during or in the 24 hours after infusion (together with the type and intensity of these side effects) | day 0 |
| Infusion's safety | proportion of patients in each group reporting any side effect during or in the 24 hours after infusion (together with the type and intensity of these side effects) | day 1 |
| Proportion of patients necessitating rescue therapy | Proportion of patients necessitating rescue therapy (infusion of ketamine combined with magnesium) | Day 15 |
| Treatment response according to initial magnesemia | magnesemia on the infusion day (D0) will be correlated with 50% response at D7-8 among patients receiving active treatment | day 7 |
| Treatment response according to initial magnesemia | magnesemia on the infusion day (D0) will be correlated with 50% response at D7-8 among patients receiving active treatment | day 8 |
| Attacks treatment consumption | Daily attacks treatment consumption (injectable sumatriptan and oxygene) | day 0 to day 90 |
| Direct medical cost | Direct medical cost (treatments, consultations, hospitalisations) in each group and cost effectiveness ratio taking 50% responder rate as efficacy criteria | day 0 to day 90 |
| Anxiety evolution | comparison of anxiety (evaluated via the HAD scale) between groups | Day 15 |
| Anxiety evolution | comparison of anxiety (evaluated via the HAD scale) between groups | Day 90 |
| depression evolution | comparison of depression (evaluated via the HAD scale) between groups | Day 15 |
| depression evolution | comparison ofdepression (evaluated via the HAD scale) between groups | Day 90 |
| Change in weekly attacks between day 14 - day 20 period compared to the pre-treatment period | Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 14 and day 20 post-reatment period and pre-treatment period. The number of weekly attacks will be evaluated using a attacks diary that patients will complete every day. | pre-treatment period and day 14 - day 20 post-treatment period |
| Change in weekly attacks between day 21 - day 27 period compared to the pre-treatment period | Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 21 and day 27 post-reatment period and pre-treatment period. The number of weekly attacks will be evaluated using a attacks diary that patients will complete every day. | pre-treatment period and day 21 - day 27 post-treatment period |
| Change in weekly attacks between day 28 - day 34 period compared to the pre-treatment period | Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 28 and day 34 post-treatment period and pre-treatment period. The number of weekly attacks will be evaluated using a attacks diary that patients will complete every day. | pre-treatment period and day 28 - day 34 post-treatment period |
| Adverse events assessment | D0 to D90 |
| assessment of blind quality | A blinding questionnaire will be systematically used to assess the quality of the blind. It will be completed by each patient 30 minutes after the end of the 1st infusion at day 0 (Visit 1). The patient will be asked what treatment he thinks he has received. | Day 0 |
| Bruges |
| 33520 |
| France |
| CHU de Clermont-Ferrand | Clermont-Ferrand | 63000 | France |
| CHRU De Lille | Lille | 59000 | France |
| Hospices civils de Lyon, Hôpital Pierre Wertheimer | Lyon | 69500 | France |
| AP-HM Marseille | Marseille | 13005 | France |
| Clinique Beau Soleil | Montpellier | 34070 | France |
| CHU de Montpellier | Montpellier | 34295 | France |
| CHU Nantes, Hopital Nord Laennec | Nantes | 44000 | France |
| Hôpital Lariboisière | Paris | 75010 | France |
| CHU Rouen | Rouen | 76100 | France |
| Hopital de Hautepierre | Strasbourg | 67098 | France |
| Hopital Pierre Paul Riquet | Toulouse | 31059 | France |
| CHU Grenoble-Alpes | Voiron | 38500 | France |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D017616 | Magnesium Compounds |
| D007287 | Inorganic Chemicals |
| D013431 | Sulfates |
| D013464 | Sulfuric Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D004364 | Pharmaceutical Preparations |