NCT02892916: POCK

Ketamine and Postoperative Cognitive Dysfunction

Completed Phase 3 Last updated 10 September 2019

What this trial tests

Phase 3 trial testing Ketamine in Post Operative Cognitive Dysfunction in 307 participants. Completed in 31 August 2019.

Timeline

20 March 2017

Primary endpoint
31 August 2019

31 August 2019

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	307
Start date	20 March 2017
Primary completion	31 August 2019
Estimated completion	31 August 2019
Sites	1 location across France

Drugs / interventions tested

• Ketamine (ketamine) — full drug profile →
• Placebo

Conditions studied

• Post Operative Cognitive Dysfunction — all drugs for Post Operative Cognitive Dysfunction →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

60 and older, any sex, with Post Operative Cognitive Dysfunction. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment.
   Safavynia SA, Goldstein PA. · · 2018 · cited 212× · PMID 30705643 · DOI 10.3389/fpsyt.2018.00752
2. An immune signature of postoperative cognitive decline: a prospective cohort study.
   Verdonk F, Cambriel A, Hedou J, Ganio E, et al · · 2024 · cited 9× · PMID 39411891 · DOI 10.1097/js9.0000000000002118
3. Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial.
   Verdonk F, Lambert P, Gakuba C, Nelson AC, et al · · 2024 · cited 7× · PMID 38710325 · DOI 10.1016/j.accpm.2024.101387