Chronic Daily HeadachePhase 3KetHeadNCT05306899
Multi-center RCT of IV Ketamine Efficacy and Safety in Chronic Daily Headaches
A Phase 3 study testing Ketamine and 0.9% Saline in people with Chronic Daily Headache, run by University Health Network, Toronto at 2 sites in Canada.
Trial summary
Chronic daily headaches (CDH) poses a significant burden on patients, healthcare systems and the society. Intravenous (IV) ketamine infusion, an intervention that is widely available and scalable, can treat CDH by reversing receptor-mediated sensitization. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Daily Headache
- What is being tested?
- Ketamine and 0.9% Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 2 sitesCanada
- Study dates
- 1 Jun 2022to 1 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years
- CDH diagnosis preceding trial enrollment with headache episodes lasting for 4 or more hours occurring on 15 or more days in a month for 3 or more months (International Headache Society-IHS criteria)
- Normal liver and kidney function tests
Who cannot join
- Pregnant or breastfeeding patients
- Pre-existing renal impairment
- Pre-existing liver impairment
- Chronic benzodiazepine or antipsychotic medication use
- History of cerebrovascular event
- Significant and untreated hypertension or severe cardiac condition
Show all 16Show fewer
- Hypothyroidism
- Glaucoma
- Concomitant use of strong CYP2B6 or CYP2C8 inhibitor
- Allergy or intolerance to ketamine
- Pheochromocytoma
- Any significant cognitive or language barriers that impede participation
- CGRP antagonist use in 1 month or Onabotulinum-toxin A 3 months before infusion
- Active diagnosis of Post-Traumatic Stress Disorder (PTSD)
- Active diagnosis of Substance Use Disorder
- Patients taking opioid medications with daily Oral Morphine Equivalents ≥80 mg
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
Women's College Hospital
Toronto, Ontario, M5S 1B2
Didem Bozak, kethead@uhn.ca
- Recruiting
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Emad Al Azazi, +1-416-603-5800 ext. 2508, kethead@uhn.ca
Anuj Bhatia, MD, PhD
About this study
Official title: A Multi-center Randomized Controlled Trial of Efficacy and Safety of Intravenous Ketamine for Chronic Daily Headaches: The KetHead Study
Chronic daily headaches (CDH) poses a significant burden on patients, healthcare systems and the society. Intravenous (IV) ketamine infusion, an intervention that is widely available and scalable, can treat CDH by reversing receptor-mediated sensitization. This study is a multicenter, placebo-controlled, parallel group randomized trial with blinding of participants and observers with the goal of comprehensively assessing the effect of high-dose IV ketamine infusion (1 mg.kg-1.h-1 for six hours) on the frequency and intensity of headaches, mood, activity, sleep, quality of life and safety of ketamine for three months after the interventions. Use of validated questionnaires, wearable technology, a research team that includes investigators with expertise in studying ketamine and in evaluating treatments for CDH and pain syndromes are some of the unique features of this project.
Our study aims to prospectively assess the efficacy and safety of high-dose intravenous ketamine infusions compared to saline infusions in participants with CDH syndrome.
Read the detailed description
The KetHead study is designed as a multi-center, placebo-controlled, superiority randomized controlled trial with two parallel groups and blinding of participants and outcome assessors. It will be conducted at two chronic pain centers, Toronto Western Hospital and Sinai Health System. Eligible patients will be identified and enrolled in the pain clinics. Randomization will take place upon patient enrollment. Treating physicians, patients, close contacts, study coordinators and primary outcome assessors will be blinded to treatment allocation.
Interventions common to both arms Participating patients will receive the infusion at the pain infusion unit at Toronto Western Hospital, under hemodynamic monitoring, supervised by an Anesthesiologist. At the start of the infusion, all patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4)22 to blind the participants and assessors to group allocation. Eight mg of ondansetron and 8 mg of dexamethasone will be administered to all participants to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events. Medications will be administered by an Anesthesiologist.
- Intervention group: For individuals randomized to the IV Ketamine group, 1 mg.kg-1 bolus will be given. This will be prepared as a syringe of 10 cc of Ketamine 10 mg/ml. This is followed by an infusion of 1 mg.kg-1.hour-1 (ketamine diluted in saline to 2 mg/mL at 0.5 mL.kg-1.hour-1) for six hours.
- Control group: For individuals in the saline infusion group, an IV bolus of 0.9% saline will be given. The volume will be the same as that of the ketamine bolus for that weight, to prevent unblinding of participants and assessors. This will be followed by an infusion 0.5 mL.kg-1.hour-1 of saline for six hours. The rate of the infusion will be the same as that of a ketamine infusion for that weight to prevent unblinding of participants and assessors.
Study personnel will assess patient and collect data throughout their enrollment in the study.
During the trial, patients will be instructed to use a pain and migraine diary for collection of migraine days, pain scores and rescue pain medication during the 12 weeks after infusion.
Patients will be assessed for collection of outcomes immediately after the infusion and at 1-month, 2-months and 3-months after infusion.
Participants in both arms will wear the actigraphy device starting on the day of infusion for one month to longitudinally assess the impact of the study treatments on sleep and activity.
- Conditions
- Chronic Daily Headache
- Being tested
- Ketamine, 0.9% Saline
- Keywords
- ketamine, migraine, daily headache, chronic pain
- Medical subject headings
- Headache Disorders, Migraine Disorders, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketamine hydrochloride
Bolus of IV Ketamine 1 mg.kg-1 (= 0.1 ml.kg-1) followed by Infusion of Ketamine 1 mg.kg-1.hour-1 (= 0.5 mL.kg-1.hour-1) for 6 hours. All patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events.
0.9% SalineOther
Also called Normal saline
Bolus of IV Saline 0.9% of 0.1 ml.kg-1 followed by Infusion of Saline 0.9% of 0.5 mL.kg-1.hour-1 for 6 hours. All patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine infusion | Active comparator | Intravenous Ketamine at a dose of 1 mg / kg / hour for six hours. Receives: Drug: Ketamine |
| Placebo infusion | Placebo comparator | 0.9% saline infusion at the same rate as the study drug group for six hours. Receives: Other: 0.9% Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in headache days between the 2 groups
Between-group difference in the number of headache days in the first 4 weeks after the infusion.
(Defined as a day in which the headache lasts 4 or more hours, or a headache of any duration for which abortive treatment (anti-inflammatories, triptans, ergot derivatives, opioids) are taken. Patients will be asked to keep track of their headache days in a diary)
Measured: At 4 weeks
Secondary outcomes (15)
Impact of ketamine on headache intensity after infusion
Impact of ketamine on headache intensity at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using Numerical Rating Scale (0-10)
Measured: At 1 month, 2 months and 3 months
Impact of ketamine on headache frequency after infusion
Impact of ketamine on headache frequency at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, as number of headache episodes per day
Measured: At 1 month, 2 months and 3 months
Impact of ketamine on headache duration after infusion
Impact of ketamine on duration of headache at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, from the headache diary maintained by patient
Measured: At 1 month, 2 months and 3 months
Impact on sleep efficiency after ketamine infusion
Impact of ketamine on efficiency of sleep at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, measured with an actigraphy device
Measured: At 1 month, 2 months and 3 months
Impact on quality of sleep after ketamine infusion
Impact of ketamine on quality of sleepat one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, assessed with the PSQI (Pittsburgh Sleep Quality Index) questionnaire
Measured: At 1 month, 2 months and 3 months
Impact on physical activity after ketamine infusion
Impact of ketamine on physical activity at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, measured with actigraphy device
Measured: At 1 month, 2 months and 3 months
Impact after ketamine infusion on daily activity
Impact of ketamine on seven daily activities (e.g. general activity, walking, mood etc.) at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, measured with Brief Pain Inventory (BPI) scale
Measured: At 1 month, 2 months and 3 months
Impact of on emotional well being (for catastrophizing) after ketamine infusion
Impact of ketamine on emotional well being at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using the PCS (pain catastrophizing scale) scale
Measured: At 1 month, 2 months and 3 months
Impact of on emotional well being for anxiety after ketamine infusion
Impact of ketamine on emotional well being at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using anxiety (GAD7- Generalized Anxiety Disorder-7) scale
Measured: At 1 month, 2 months and 3 months
Impact of on emotional well being for depression after ketamine infusion
Impact of ketamine on emotional well being at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using depression (PHQ9-Patient Health Questionnaire9) questionnaire
Measured: At 1 month, 2 months and 3 months
Impact of ketamine infusion on patient satisfaction
Impact of ketamine on patient satisfaction at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using global improvement (PGIC) scales
Measured: At 1 month, 2 months and 3 months
Impact on quality of life after ketamine infusion
Impact of ketamine on quality of life at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using EQ-5D (European Quality of life) questionnaire
Measured: At 1 month, 2 months and 3 months
Impact of ketamine infusion on analgesic consumption
Impact of ketamine on analgesic consumption at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using name and dose of the analgesic use
Measured: At 1 month, 2 months and 3 months
Side effects after ketamine infusion
Side effects after the ketamine infusion as assessed using Bowdle questionnaire
Measured: Immediately after infusion and after 1 week
Side effects after ketamine infusion
Dissociative side effects assessed after the ketamine infusion, using the CADSS (Clinician Administered Dissociative States Scale) checklist
Measured: Immediately after the infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start1 Jun 2022
- Primary completion1 Feb 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Chronic Daily HeadacheStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- The Canadian Pain Society, Pfizer
- Responsible party
- Sponsor
- Investigators
- Anuj Bhatia, MD, PhD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05306899
- Sponsor's protocol ID
- 21-5523
- Acronym
- KetHead
- Status last verified
- Oct 2025
- First submitted
- 2 Mar 2022
- Last updated
- 8 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Study results will first be disseminated at the local, national and international conferences and submitted for publication in a peer-reviewed journal.
Publications
Schwenk ES, Dayan AC, Rangavajjula A, Torjman MC, Hernandez MG, Lauritsen CG, Silberstein SD, Young W, Viscusi ER. Ketamine for Refractory Headache: A Retrospective Analysis. Reg Anesth Pain Med. 2018 Nov;43(8):875-879. doi: 10.1097/AAP.0000000000000827.
PubMed 29923953Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine Infusions for Treatment Refractory Headache. Headache. 2017 Feb;57(2):276-282. doi: 10.1111/head.13013. Epub 2016 Dec 27.
PubMed 28025837Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesth Analg. 2019 Jul;129(1):241-254. doi: 10.1213/ANE.0000000000004185.
PubMed 31082965Vekhova KA, Namiot ED, Jonsson J, Schioth HB. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.
PubMed 39428602Hoydonckx Y, Singh M, Gilron I, Khan J, Narouze S, Dahan A, Curtis K, Cao X, Kara J, Bhatia A. Trial protocol for a multicenter randomized controlled trial to assess the efficacy and safety of intravenous ketamine for chronic daily headaches: the "KetHead" trial. Trials. 2023 Mar 1;24(1):155. doi: 10.1186/s13063-023-07186-3.
PubMed 36855160
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center Randomized Controlled Trial of Efficacy and Safety of Intravenous Ketamine for Chronic Daily Headaches: The KetHead Study
- ClinicalTrials.gov ID
- NCT05306899
- Acronym / sponsor ID
- KetHead / 21-5523
- Conditions
- Chronic Daily Headache
- Keywords
- ketamine, migraine, daily headache, chronic pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- The Canadian Pain Society, Pfizer
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 1 Feb 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 1 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic daily headaches (CDH) poses a significant burden on patients, healthcare systems and the society. Intravenous (IV) ketamine infusion, an intervention that is widely available and scalable, can treat CDH by reversing receptor-mediated sensitization. This study is a multicenter, placebo-controlled, parallel group randomized trial with blinding of participants and observers with the goal of comprehensively assessing the effect of high-dose IV ketamine infusion (1 mg.kg-1.h-1 for six hours) on the frequency and intensity of headaches, mood, activity, sleep, quality of life and safety of ketamine for three months after the interventions. Use of validated questionnaires, wearable technology, a research team that includes investigators with expertise in studying ketamine and in evaluating treatments for CDH and pain syndromes are some of the unique features of this project.
Our study aims to prospectively assess the efficacy and safety of high-dose intravenous ketamine infusions compared to saline infusions in participants with CDH syndrome.
Detailed description
The KetHead study is designed as a multi-center, placebo-controlled, superiority randomized controlled trial with two parallel groups and blinding of participants and outcome assessors. It will be conducted at two chronic pain centers, Toronto Western Hospital and Sinai Health System. Eligible patients will be identified and enrolled in the pain clinics. Randomization will take place upon patient enrollment. Treating physicians, patients, close contacts, study coordinators and primary outcome assessors will be blinded to treatment allocation.
Interventions common to both arms Participating patients will receive the infusion at the pain infusion unit at Toronto Western Hospital, under hemodynamic monitoring, supervised by an Anesthesiologist. At the start of the infusion, all patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4)22 to blind the participants and assessors to group allocation. Eight mg of ondansetron and 8 mg of dexamethasone will be administered to all participants to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events. Medications will be administered by an Anesthesiologist.
- Intervention group: For individuals randomized to the IV Ketamine group, 1 mg.kg-1 bolus will be given. This will be prepared as a syringe of 10 cc of Ketamine 10 mg/ml. This is followed by an infusion of 1 mg.kg-1.hour-1 (ketamine diluted in saline to 2 mg/mL at 0.5 mL.kg-1.hour-1) for six hours.
- Control group: For individuals in the saline infusion group, an IV bolus of 0.9% saline will be given. The volume will be the same as that of the ketamine bolus for that weight, to prevent unblinding of participants and assessors. This will be followed by an infusion 0.5 mL.kg-1.hour-1 of saline for six hours. The rate of the infusion will be the same as that of a ketamine infusion for that weight to prevent unblinding of participants and assessors.
Study personnel will assess patient and collect data throughout their enrollment in the study.
During the trial, patients will be instructed to use a pain and migraine diary for collection of migraine days, pain scores and rescue pain medication during the 12 weeks after infusion.
Patients will be assessed for collection of outcomes immediately after the infusion and at 1-month, 2-months and 3-months after infusion.
Participants in both arms will wear the actigraphy device starting on the day of infusion for one month to longitudinally assess the impact of the study treatments on sleep and activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine infusion | Active comparator | Drug: KetamineIntravenous Ketamine at a dose of 1 mg / kg / hour for six hours. |
| Placebo infusion | Placebo comparator | Other: 0.9% Saline0.9% saline infusion at the same rate as the study drug group for six hours. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18-75 years
- CDH diagnosis preceding trial enrollment with headache episodes lasting for 4 or more hours occurring on 15 or more days in a month for 3 or more months (International Headache Society-IHS criteria)
- Normal liver and kidney function tests
Key exclusion criteria (16 listed)
- Pregnant or breastfeeding patients
- Pre-existing renal impairment
- Pre-existing liver impairment
- Chronic benzodiazepine or antipsychotic medication use
- History of cerebrovascular event
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Ketamine hydrochlorideBolus of IV Ketamine 1 mg.kg-1 (= 0.1 ml.kg-1) followed by Infusion of Ketamine 1 mg.kg-1.hour-1 (= 0.5 mL.kg-1.hour-1) for 6 hours. All patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events. | Drug | Ketamine infusion |
| 0.9% SalineAlso: Normal salineBolus of IV Saline 0.9% of 0.1 ml.kg-1 followed by Infusion of Saline 0.9% of 0.5 mL.kg-1.hour-1 for 6 hours. All patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events. | Other | Placebo infusion |
Primary outcome
Difference in headache days between the 2 groups
Time frame: At 4 weeks
Between-group difference in the number of headache days in the first 4 weeks after the infusion. (Defined as a day in which the headache lasts 4 or more hours, or a headache of any duration for which abortive treatment (anti-inflammatories, triptans, ergot derivatives, opioids) are taken. Patients will be asked to keep track of their headache days in a diary)
15 secondary outcomes
Impact of ketamine on headache intensity after infusion
Time frame: At 1 month, 2 months and 3 months
Impact of ketamine on headache frequency after infusion
Time frame: At 1 month, 2 months and 3 months
Impact of ketamine on headache duration after infusion
Time frame: At 1 month, 2 months and 3 months
Impact on sleep efficiency after ketamine infusion
Time frame: At 1 month, 2 months and 3 months
Impact on quality of sleep after ketamine infusion
Time frame: At 1 month, 2 months and 3 months
Impact on physical activity after ketamine infusion
Time frame: At 1 month, 2 months and 3 months
Impact after ketamine infusion on daily activity
Time frame: At 1 month, 2 months and 3 months
Impact of on emotional well being (for catastrophizing) after ketamine infusion
Time frame: At 1 month, 2 months and 3 months
Impact of on emotional well being for anxiety after ketamine infusion
Time frame: At 1 month, 2 months and 3 months
Impact of on emotional well being for depression after ketamine infusion
Time frame: At 1 month, 2 months and 3 months
Impact of ketamine infusion on patient satisfaction
Time frame: At 1 month, 2 months and 3 months
Impact on quality of life after ketamine infusion
Time frame: At 1 month, 2 months and 3 months
Impact of ketamine infusion on analgesic consumption
Time frame: At 1 month, 2 months and 3 months
Side effects after ketamine infusion
Time frame: Immediately after infusion and after 1 week
Side effects after ketamine infusion
Time frame: Immediately after the infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2026.
- Results publication: PubMed 29923953Schwenk ES, Dayan AC, Rangavajjula A, Torjman MC, Hernandez MG, Lauritsen CG, Silberstein SD, Young W, Viscusi ER. Ketamine for Refractory Headache: A Retrospective Analysis. Reg Anesth Pain Med. 2018 Nov;43(8):875-879. doi: 10.1097/AAP.0000000000000827.
- Results publication: PubMed 28025837Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine Infusions for Treatment Refractory Headache. Headache. 2017 Feb;57(2):276-282. doi: 10.1111/head.13013. Epub 2016 Dec 27.
- Results publication: PubMed 31082965Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesth Analg. 2019 Jul;129(1):241-254. doi: 10.1213/ANE.0000000000004185.
- Derived from this study: PubMed 39428602Vekhova KA, Namiot ED, Jonsson J, Schioth HB. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.
- Derived from this study: PubMed 36855160Hoydonckx Y, Singh M, Gilron I, Khan J, Narouze S, Dahan A, Curtis K, Cao X, Kara J, Bhatia A. Trial protocol for a multicenter randomized controlled trial to assess the efficacy and safety of intravenous ketamine for chronic daily headaches: the "KetHead" trial. Trials. 2023 Mar 1;24(1):155. doi: 10.1186/s13063-023-07186-3.
- Individual participant dataSharing planned: No. Study results will first be disseminated at the local, national and international conferences and submitted for publication in a peer-reviewed journal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anuj Bhatia, MD, PhD principal investigator
University Health Network, Toronto
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ketamine and 0.9% Saline in people with Chronic Daily Headache, run by University Health Network, Toronto at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Emad Al Azazi (+1 (416) 603 5800 ext. 2508, KetHead@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in headache days between the 2 groups (time frame: At 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05306899, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.