Post Operative Cognitive DysfunctionPhase 3POCKNCT02892916
Ketamine and Postoperative Cognitive Dysfunction
A Phase 3 study testing Ketamine in people with Post Operative Cognitive Dysfunction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Over 30 million patients require a major surgery annually in the US alone and more than half of them are performed in patients over 60 years of age. Post-operative cognitive dysfunction (POCD) is a keystone complication of these surgeries and affects up to 40% of surgical patients aged over 60 years on discharge from… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Post Operative Cognitive Dysfunction
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 307 participants
- Where
- 1 siteFrance
- Study dates
- 20 Mar 2017to 31 Aug 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 60 years and older
- Competent to provide informed consent
- Undergoing major elective orthopaedic surgery under general anaesthesia
- Patients with and without pre-existing neurodegenerative disease
Who cannot join
- Moribund patient or patient under palliative care
- Expected length of stay at hospital < 48 hours
- Patient under tutorship or curatorship
- Surgical procedure performed under spinal or epidural anaesthesia without general anaesthesia
- Emergency surgery (i.e. emergency hip fracture)
- Patients with a known allergy to ketamine
Show all 16Show fewer
- Contraindication for ketamine: severe, uncontrolled arterial hypertension or severe heart (FEVG<25%)
- Patient with glaucoma or history of thyrotoxicosis
- Severe audition or vision disorder
- Patients with drug misuse history (e.g., ketamine, cocaine, heroin, amphetamine, methamphetamine, MDMA (methylenedioxymethamphetamine), phencyclidine, lysergic acid, mescaline, psilocybin)
- Patients taking anti-psychotic medications (e.g., chlorpromazine, clozapine, olanzapine, risperidone, haloperidol, quetiapine, risperidone, paliperidone, amisulpride, sertindole)
- Patients with severe alcohol liver disease (TP<50% and or bilirubin > 50 µmol/L)
- Pregnant or breast-feeding woman
- Patient not speaking French
- Absence of informed consent or request to not participate to the study
- Non affiliation to the social security
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Prevention of Post Operative Cognitive Dysfunction by Ketamine: a Prospective Multicenter Randomized Blinded Placebo-controlled Trial in Elderly Patients Undergoing Elective Orthopaedic Surgery
Over 30 million patients require a major surgery annually in the US alone and more than half of them are performed in patients over 60 years of age. Post-operative cognitive dysfunction (POCD) is a keystone complication of these surgeries and affects up to 40% of surgical patients aged over 60 years on discharge from the hospital. Despite controlled longitudinal studies have shown that POCD is transient, it is associated with delirium, higher mortality, earlier retirement, and greater utilization of social financial assistance The pathophysiology of persistent postoperative cognitive dysfunction and causal relationship between POCD and delirium remain incompletely understood. Identified clinical risk factors for both include advanced age, type of surgery, preexisting cognitive impairment, and drug addiction. We and others have provided evidence that the inflammatory response triggered by surgical trauma and pain may contribute to the development of delirium and cognitive impairment after surgery.
Ketamine, a N-methyl-D-aspartic acid receptor antagonist, is commonly used in anaesthesia and postoperative analgesia. By reducing both pain and glutamate excitotoxic effects on neuronal and microglial brain cells, it contributes to tone down the neuroinflammatory process associated with surgery. A recent body of evidence has shown that ketamine reduces the depressive-like behavior induced by inflammatory or stress-induced stimuli in mice. Ketamine was also found to reduce levels of inflammatory biomarkers in cardiac surgical patients.
Orthopaedic surgery is a high-risk situation for developing postoperative cognitive dysfunction. In patients undergoing non-cardiac surgery, the prevalence of POCD is 26% one week after surgery and decreased to 10% at 3 months postoperatively, and a similar prevalence is found 12 months after the operation. Postoperative delirium is associated with an increased risk of POCD. Hundred thousands of patients > 60 years undergo elective orthopaedic procedures per year around the world.
Read the detailed description
The design consists in a prospective multicenter randomized blinded placebo-controlled trial in elderly patients undergoing elective orthopaedic surgery.
Patients will be informed at the pre-anaesthetic consultation, 7 to 30 days before surgery. They will be randomized the day before surgery. Cognitive and depressive status at baseline will be assessed precisely the day pior to surgery with cognitive tests. Self-administered scores will be recorded to evaluate depression, anxiety, and quality of life.
At the day of surgery, patients in the experimental group will receive a bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia. Patients in the control group will receive a bolus of an intravenous normal saline solution following induction of anaesthesia.
From D0 (2 hours after surgery end) to D7 or discharge from the hospital if earlier, delirium, pain, adverse clinical and psychiatric events will be measured and recorded.
Cognitive functions, neuropathic pain, depression, anxiety and quality of life will be assessed at D7 or discharge from the hospital if earlier and D90.
Inflammatory markers will be measured before surgery, at D1, D7 or discharge from the hospital if earlier and D90.
- Conditions
- Post Operative Cognitive Dysfunction
- Being tested
- Ketamine, Placebo
- Keywords
- Post-operative cognitive dysfunction (POCD), Delirium, Ketamine, Elective orthopaedic surgery
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketamine hydrochloride
A bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia.
PlaceboDrug
Also called Normal saline solution
A bolus of an intravenous normal saline solution following induction of anaesthesia.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Patients in this experimental group will receive a bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia. Receives: Drug: Ketamine |
| Placebo | Placebo comparator | Patients in this control group will receive a bolus of an intravenous normal saline solution following induction of anaesthesia. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of early postoperative cognitive dysfunction
POCD assessed using MoCA (Montreal Cognitive Assessment) test and others cognitive tests included in the calculation of the combined Z-score
Measured: Days 7 and 90 after surgery
Secondary outcomes (17)
Post-operative cognitive dysfunction type
The evaluation should be based on differences between pre- and postoperative performance (7 days or at discharge from the hospital if earlier and 3 months or earlier at the surgical follow-up visit depending on the practices of the different centers).
Measured: Days 7 and 90 after surgery
Post-operative cognitive dysfunction severity
The evaluation should be based on differences between pre- and postoperative performance (7 days or at discharge from the hospital if earlier and 3 months or earlier at the surgical follow-up visit depending on the practices of the different centers).
Measured: Days 7 and 90 after surgery
The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
Measurements will start from postoperative day 0 two hours after the end of surgery to day 7 or discharge from the hospital if earlier, twice daily (morning and evening) with at least 6 hours between two consecutive measurements.
Measured: Days 7 before surgery or discharge from the hospital
Early postoperative delirium
Patients with at least one episode of delirium measured by CAM (Confusion Assessment Method) or CAM-ICU (adaptation used in Intensive Care Unit) scores between day 0 and day 7
Measured: 7 days after surgery
Depression
Depression assessed using the Geriatric Depression Scale (GDS)
Measured: Days 7 and 90 after surgery
Anxiety
Anxiety assessed using the Hospital and Anxiety Depression Scale.
Measured: Days 7 and 90 after surgery
Pain status: Visual Analog Scale
Pain scores assessed by the patient-reported Visual Analog Scale. Neuropathic pain at 3 months measured by the DN4 (Douleur Neuropathique en 4 questions) questionnaire.
Measured: Day prior to surgery, at days 7 and 90 after surgery
Time from surgery to POCD.
Time of occurrence of POCD (early or late) and his association with postoperative delirium
Measured: Days 7 and 90 after surgery
Pre-existing cognitive status
Pre-existing cognitive status measured by the preoperative combined Z-score for cognitive functions and his association with the occurrence of postoperative delirium
Measured: Days 7 and 90 after surgery
Preoperative Charlson's score for comorbidities
Preoperative Charlson's sore for comorbidities and his association with the occurrence of postoperative delirium
Measured: Days 7 and 90 after surgery
Intraoperative serious adverse events
Intraoperative serious adverse events such as bleeding requiring at least 2 red cell units or unexpected prolonged duration of surgery and their association with postoperative delirium.
Measured: Day 7
Postoperative adverse events
Early post-operative complications (reoperation, hospital readmission, bleeding, transfusion, sepsis, hypoxemia, sodium disorders, specific medications, presence or absence of a specific rehabilitation program) recorded from patients' charts and their association with postoperative delirium.
Measured: Day 7
Hospital length of stay
Hospital length of stay assessed from patients' medical administrative data in days
Measured: Day 90
Cause of death
Cause of death as postoperative cardio-respiratory arrest and degradation of the general condition
Measured: Day 90
Hospital readmission
Hospital readmission during the follow up, whatever the etiology
Measured: Day 90
Inflammatory biomarkers
Inflammatory biomarkers (C Reactive Protein, Interleukin-6, Interleukin-2, TNFalpha, B-type natriuretic peptide and Troponin) levels and their association with the occurrence of postoperative delirium and long term POCD
Measured: Day 90
Quality of life evaluated thanks to the SF-36 scale
Quality of life evaluated thanks to the SF-36 scale is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2016 (estimated)
- Study start20 Mar 2017
- Primary completion31 Aug 2019
- Study completion31 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Post Operative Cognitive DysfunctionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 307 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Franck Verdonk, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02892916
- Sponsor's protocol ID
- P150910
- Other IDs
- 2016-000691-16, PHRC-15-15-0534, 2016
- Acronym
- POCK
- Status last verified
- Sep 2019
- First submitted
- 31 Jul 2016
- Last updated
- 10 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014 Sep-Dec;8(3):283-90. doi: 10.4103/0259-1162.143110.
PubMed 25886322Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, Bertrand L, Beltramini A, Gamand P, Albizzati S, Perdrizet D, Lebail G, Chollet-Xemard C, Maxime V, Brun-Buisson C, Lefrant JY, Bollaert PE, Megarbane B, Ricard JD, Anguel N, Vicaut E, Adnet F; KETASED Collaborative Study Group. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009 Jul 25;374(9686):293-300. doi: 10.1016/S0140-6736(09)60949-1. Epub 2009 Jul 1.
PubMed 19573904Riou B, Lecarpentier Y, Viars P. Inotropic effect of ketamine on rat cardiac papillary muscle. Anesthesiology. 1989 Jul;71(1):116-25. doi: 10.1097/00000542-198907000-00020.
PubMed 2751123Riou B, Viars P, Lecarpentier Y. Effects of ketamine on the cardiac papillary muscle of normal hamsters and those with cardiomyopathy. Anesthesiology. 1990 Nov;73(5):910-8. doi: 10.1097/00000542-199011000-00019.
PubMed 2240681Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, Alkondon M, Yuan P, Pribut HJ, Singh NS, Dossou KS, Fang Y, Huang XP, Mayo CL, Wainer IW, Albuquerque EX, Thompson SM, Thomas CJ, Zarate CA Jr, Gould TD. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016 May 26;533(7604):481-6. doi: 10.1038/nature17998. Epub 2016 May 4.
PubMed 27144355Harraz MM, Tyagi R, Cortes P, Snyder SH. Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation. Mol Psychiatry. 2016 Mar;21(3):313-9. doi: 10.1038/mp.2015.211. Epub 2016 Jan 19.
PubMed 26782056Zorumski CF, Nagele P, Mennerick S, Conway CR. Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy. Front Psychiatry. 2015 Dec 9;6:172. doi: 10.3389/fpsyt.2015.00172. eCollection 2015.
PubMed 26696909Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, Warltier DC, Pagel PS. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009 Oct;23(5):651-7. doi: 10.1053/j.jvca.2008.12.021. Epub 2009 Feb 23.
PubMed 19231245Arrowsmith JE, Harrison MJ, Newman SP, Stygall J, Timberlake N, Pugsley WB. Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during coronary artery bypass in 171 patients. Stroke. 1998 Nov;29(11):2357-62. doi: 10.1161/01.str.29.11.2357.
PubMed 9804648Verdonk F, Lambert P, Gakuba C, Nelson AC, Lescot T, Garnier F, Constantin JM, Saurel D, Lasocki S, Rineau E, Diemunsch P, Dreyfuss L, Tavernier B, Bezu L, Josserand J, Mebazaa A, Coroir M, Nouette-Gaulain K, Macouillard G, Glasman P, Lemesle D, Minville V, Cuvillon P, Gaudilliere B, Quesnel C, Abdel-Ahad P, Sharshar T, Molliex S, Gaillard R, Mantz J. Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial. Anaesth Crit Care Pain Med. 2024 Aug;43(4):101387. doi: 10.1016/j.accpm.2024.101387. Epub 2024 May 6.
PubMed 38710325
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Prevention of Post Operative Cognitive Dysfunction by Ketamine: a Prospective Multicenter Randomized Blinded Placebo-controlled Trial in Elderly Patients Undergoing Elective Orthopaedic Surgery
- ClinicalTrials.gov ID
- NCT02892916
- Acronym / sponsor ID
- POCK / P150910
- Conditions
- Post Operative Cognitive Dysfunction
- Keywords
- Post-operative cognitive dysfunction (POCD), Delirium, Ketamine, Elective orthopaedic surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 307 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- 20 Mar 2017 (actual)
- Primary completion
- 31 Aug 2019 (actual)
- Study completion
- 31 Aug 2019 (actual)
- First posted
- 8 Sep 2016 (estimated)
- 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.
Over 30 million patients require a major surgery annually in the US alone and more than half of them are performed in patients over 60 years of age. Post-operative cognitive dysfunction (POCD) is a keystone complication of these surgeries and affects up to 40% of surgical patients aged over 60 years on discharge from the hospital. Despite controlled longitudinal studies have shown that POCD is transient, it is associated with delirium, higher mortality, earlier retirement, and greater utilization of social financial assistance The pathophysiology of persistent postoperative cognitive dysfunction and causal relationship between POCD and delirium remain incompletely understood. Identified clinical risk factors for both include advanced age, type of surgery, preexisting cognitive impairment, and drug addiction. We and others have provided evidence that the inflammatory response triggered by surgical trauma and pain may contribute to the development of delirium and cognitive impairment after surgery.
Ketamine, a N-methyl-D-aspartic acid receptor antagonist, is commonly used in anaesthesia and postoperative analgesia. By reducing both pain and glutamate excitotoxic effects on neuronal and microglial brain cells, it contributes to tone down the neuroinflammatory process associated with surgery. A recent body of evidence has shown that ketamine reduces the depressive-like behavior induced by inflammatory or stress-induced stimuli in mice. Ketamine was also found to reduce levels of inflammatory biomarkers in cardiac surgical patients.
Orthopaedic surgery is a high-risk situation for developing postoperative cognitive dysfunction. In patients undergoing non-cardiac surgery, the prevalence of POCD is 26% one week after surgery and decreased to 10% at 3 months postoperatively, and a similar prevalence is found 12 months after the operation. Postoperative delirium is associated with an increased risk of POCD. Hundred thousands of patients > 60 years undergo elective orthopaedic procedures per year around the world.
Detailed description
The design consists in a prospective multicenter randomized blinded placebo-controlled trial in elderly patients undergoing elective orthopaedic surgery.
Patients will be informed at the pre-anaesthetic consultation, 7 to 30 days before surgery. They will be randomized the day before surgery. Cognitive and depressive status at baseline will be assessed precisely the day pior to surgery with cognitive tests. Self-administered scores will be recorded to evaluate depression, anxiety, and quality of life.
At the day of surgery, patients in the experimental group will receive a bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia. Patients in the control group will receive a bolus of an intravenous normal saline solution following induction of anaesthesia.
From D0 (2 hours after surgery end) to D7 or discharge from the hospital if earlier, delirium, pain, adverse clinical and psychiatric events will be measured and recorded.
Cognitive functions, neuropathic pain, depression, anxiety and quality of life will be assessed at D7 or discharge from the hospital if earlier and D90.
Inflammatory markers will be measured before surgery, at D1, D7 or discharge from the hospital if earlier and D90.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetaminePatients in this experimental group will receive a bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia. |
| Placebo | Placebo comparator | Drug: PlaceboPatients in this control group will receive a bolus of an intravenous normal saline solution following induction of anaesthesia. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients 60 years and older
- Competent to provide informed consent
- Undergoing major elective orthopaedic surgery under general anaesthesia
- Patients with and without pre-existing neurodegenerative disease
Key exclusion criteria (16 listed)
- Moribund patient or patient under palliative care
- Expected length of stay at hospital < 48 hours
- Patient under tutorship or curatorship
- Surgical procedure performed under spinal or epidural anaesthesia without general anaesthesia
- Emergency surgery (i.e. emergency hip fracture)
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 hydrochlorideA bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia. | Drug | Ketamine |
| PlaceboAlso: Normal saline solutionA bolus of an intravenous normal saline solution following induction of anaesthesia. | Drug | Placebo |
Primary outcome
Proportion of early postoperative cognitive dysfunction
Time frame: Days 7 and 90 after surgery
POCD assessed using MoCA (Montreal Cognitive Assessment) test and others cognitive tests included in the calculation of the combined Z-score
17 secondary outcomes
Post-operative cognitive dysfunction type
Time frame: Days 7 and 90 after surgery
Post-operative cognitive dysfunction severity
Time frame: Days 7 and 90 after surgery
The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
Time frame: Days 7 before surgery or discharge from the hospital
Early postoperative delirium
Time frame: 7 days after surgery
Depression
Time frame: Days 7 and 90 after surgery
Anxiety
Time frame: Days 7 and 90 after surgery
Pain status: Visual Analog Scale
Time frame: Day prior to surgery, at days 7 and 90 after surgery
Time from surgery to POCD.
Time frame: Days 7 and 90 after surgery
Pre-existing cognitive status
Time frame: Days 7 and 90 after surgery
Preoperative Charlson's score for comorbidities
Time frame: Days 7 and 90 after surgery
Intraoperative serious adverse events
Time frame: Day 7
Postoperative adverse events
Time frame: Day 7
Hospital length of stay
Time frame: Day 90
Cause of death
Time frame: Day 90
Hospital readmission
Time frame: Day 90
Inflammatory biomarkers
Time frame: Day 90
Quality of life evaluated thanks to the SF-36 scale
Time frame: Day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Background: PubMed 25886322Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014 Sep-Dec;8(3):283-90. doi: 10.4103/0259-1162.143110.
- Background: PubMed 19573904Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, Bertrand L, Beltramini A, Gamand P, Albizzati S, Perdrizet D, Lebail G, Chollet-Xemard C, Maxime V, Brun-Buisson C, Lefrant JY, Bollaert PE, Megarbane B, Ricard JD, Anguel N, Vicaut E, Adnet F; KETASED Collaborative Study Group. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009 Jul 25;374(9686):293-300. doi: 10.1016/S0140-6736(09)60949-1. Epub 2009 Jul 1.
- Background: PubMed 2751123Riou B, Lecarpentier Y, Viars P. Inotropic effect of ketamine on rat cardiac papillary muscle. Anesthesiology. 1989 Jul;71(1):116-25. doi: 10.1097/00000542-198907000-00020.
- Background: PubMed 2240681Riou B, Viars P, Lecarpentier Y. Effects of ketamine on the cardiac papillary muscle of normal hamsters and those with cardiomyopathy. Anesthesiology. 1990 Nov;73(5):910-8. doi: 10.1097/00000542-199011000-00019.
- Background: PubMed 27144355Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, Alkondon M, Yuan P, Pribut HJ, Singh NS, Dossou KS, Fang Y, Huang XP, Mayo CL, Wainer IW, Albuquerque EX, Thompson SM, Thomas CJ, Zarate CA Jr, Gould TD. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016 May 26;533(7604):481-6. doi: 10.1038/nature17998. Epub 2016 May 4.
- Background: PubMed 26782056Harraz MM, Tyagi R, Cortes P, Snyder SH. Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation. Mol Psychiatry. 2016 Mar;21(3):313-9. doi: 10.1038/mp.2015.211. Epub 2016 Jan 19.
- Background: PubMed 26696909Zorumski CF, Nagele P, Mennerick S, Conway CR. Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy. Front Psychiatry. 2015 Dec 9;6:172. doi: 10.3389/fpsyt.2015.00172. eCollection 2015.
- Background: PubMed 19231245Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, Warltier DC, Pagel PS. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009 Oct;23(5):651-7. doi: 10.1053/j.jvca.2008.12.021. Epub 2009 Feb 23.
- Background: PubMed 9804648Arrowsmith JE, Harrison MJ, Newman SP, Stygall J, Timberlake N, Pugsley WB. Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during coronary artery bypass in 171 patients. Stroke. 1998 Nov;29(11):2357-62. doi: 10.1161/01.str.29.11.2357.
- Derived from this study: PubMed 38710325Verdonk F, Lambert P, Gakuba C, Nelson AC, Lescot T, Garnier F, Constantin JM, Saurel D, Lasocki S, Rineau E, Diemunsch P, Dreyfuss L, Tavernier B, Bezu L, Josserand J, Mebazaa A, Coroir M, Nouette-Gaulain K, Macouillard G, Glasman P, Lemesle D, Minville V, Cuvillon P, Gaudilliere B, Quesnel C, Abdel-Ahad P, Sharshar T, Molliex S, Gaillard R, Mantz J. Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial. Anaesth Crit Care Pain Med. 2024 Aug;43(4):101387. doi: 10.1016/j.accpm.2024.101387. Epub 2024 May 6.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Franck Verdonk, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site 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 in people with Post Operative Cognitive Dysfunction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 4 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: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of early postoperative cognitive dysfunction (time frame: Days 7 and 90 after surgery). 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 NCT02892916, which also lists 10 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 10 Sep 2019.