The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study

Mild Cognitive Impairment Clinical Trial

Official title:

The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05574400
• Other study ID #: HUM00218290
• Secondary ID: R01AG075005
• Status: Recruiting
• Phase: Phase 2
• Start date: February 20, 2023
• Est. completion date: May 31, 2026

Study information

• Verified date: March 2024
• Source: University of Michigan
• Contact: Phillip Vlisides, MD
• Phone: (734) 936-4280
• Email: pvliside[@]umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to test the effects of caffeine on neurocognitive and clinical recovery after major surgery. Specifically, this trial tests the primary hypothesis that caffeine will reduce the incidence of postoperative delirium.

Description:

Delirium is a syndrome characterized by failure of basic cognitive functions that affects approximately 20-50% of older surgical patients. Delirium during surgical recovery is associated with increased mortality, cognitive and functional decline, and prolonged hospitalization. In fact, 3-year survival rates for acutely hospitalized patients with delirium, and subsyndromal delirium, are both less than 50%. Older age is predictive of delirium after surgery, and with aging surgical populations, the incidence of postoperative delirium and related complications are likely to increase in the coming years.

Caffeine represents a novel, neurobiologically informed candidate intervention for reducing risk of early postoperative delirium. Caffeine promotes arousal via adenosine receptor antagonism and improves cognitive function concurrent with increased cortical cholinergic tone. Our preliminary data suggest that caffeine reduces risk of postanesthesia care unit (PACU) delirium in adult non-cardiac surgery patients by optimizing cortical dynamics for cognition. Caffeine also optimizes key neurocognitive processes that support information processing and may improve other, related aspects of clinical recovery, such as rebound headache in habitual caffeine users. The objective of this trial is to thus test the effects of caffeine on neurocognitive and clinical recovery after major surgery. Specifically, the primary hypothesis is that caffeine will reduce the incidence of postoperative delirium. The secondary objectives are to (1) test whether caffeine positively impacts the quality of postoperative recovery via validated patient-reported measures and (2) identify neural correlates of delirium and Mild Cognitive Impairment via advanced electroencephalographic (EEG) analysis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: May 31, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

1. Adult (>/= 70 years old) undergoing non-cardiac, non-intracranial neurologic, non-major vascular surgery requiring general anesthesia with a planned admission for at least 48 hours.

2. Stated willingness to comply with all study procedures and availability for the duration of the study.

3. Provision of signed and dated informed consent form.

Exclusion Criteria:

1. Emergency surgery

2. Outpatient surgery

3. Severe cognitive impairment precluding the capacity for informed consent

4. Seizure disorder history

5. Intolerance or allergy to caffeine (based on subjective reporting or objective documentation)

6. Weight >130 kg (as a 3 mg/kg dose would approach the upper limit of daily intake recommended by the FDA)

7. Enrollment in conflicting research study

8. Patients in acute liver failure

9. Acute kidney injury preoperatively

10. Diagnosis of pheochromocytoma

11. Severe audiovisual impairment

12. Non-English speaking

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Delirium
• Emergence Delirium
• Mild Cognitive Impairment
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction
• Postoperative Delirium

Intervention

Drug:
• Dextrose Water
Dextrose 5% in water
• Caffeine citrate
Low-dose caffeine citrate (1.5 mg/kg)
• Caffeine citrate
High-dose Caffeine citrate (3 mg/kg)

Locations

Country	Name	City	State
United States	Michigan Medicine	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Kim H, McKinney A, Brooks J, Mashour GA, Lee U, Vlisides PE. Delirium, Caffeine, and Perioperative Cortical Dynamics. Front Hum Neurosci. 2021 Dec 20;15:744054. doi: 10.3389/fnhum.2021.744054. eCollection 2021. — View Citation

Vlisides PE, Li D, McKinney A, Brooks J, Leis AM, Mentz G, Tsodikov A, Zierau M, Ragheb J, Clauw DJ, Avidan MS, Vanini G, Mashour GA. The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial. Anesth Analg. 2021 Jul 1;133(1):233-242. doi: 10.1213/ANE.0000000000005532. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anesthetic Emergence	Time (minutes) from surgical closure to extubation	Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes
Other	Pulmonary Complications	Composite outcome (yes/no) of any of the following: airway adjunct use, unplanned continuous positive airway pressure device, unplanned humidified high-flow oxygen, need for bag-mask ventilation, or reintubation	From extubation until end of postanesthesia care unit stay
Other	Hospital Length of Stay	Total number of days (n) spent in the hospital, up to 30 days	Morning of surgery until day of hospital discharge, up to 30 days
Other	Discharge Disposition	Proportion of patients in each group (%) discharged somewhere other than home (e.g., Long-Term Care Facility), up to 30 days	Day of hospital discharge, up to 30 days
Other	30-Day Cognitive Function	Cognitive function score based on the Montreal Cognitive Assessment (n, 0-30, with higher scores reflecting higher cognitive function)	30 days after hospital discharge
Other	30-Day Physical Function	Physical function score based on the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function 10a score (n, 10-50, with higher score indicating better physical function)	30 days after hospital discharge
Primary	Delirium	Any positive delirium screen (yes/no) as determined by the long-form Confusion Assessment Method (CAM)	Day of surgery through afternoon of postoperative day three
Secondary	Delirium Severity	For all participants screened for delirium, the associated severity score will be recorded using the Confusion Assessment Method Long Form Severity Score (CAM-S) (n, 0-19, with higher number indicating more severe delirium)	Day of surgery through afternoon of postoperative day three
Secondary	Delirium Duration	The cumulative number of days (n) with a positive delirium screen will be calculated for all participants	Day of surgery through afternoon of postoperative day three
Secondary	Patient-Reported Quality of Recovery	Assessed via the 15-item Quality of Recovery Score (n, 0-150, with higher number indicating better quality of recovery from the patient perspective)	Preoperative baseline through postoperative day three afternoon
Secondary	Sedation	Any positive screen based on the Richmond Agitation Sedation Scale (RASS; n, -5 to +4). Scores from -5 to -2 will count as a positive screen for sedation.	Preoperative baseline through postoperative day three afternoon
Secondary	Agitation	Any positive screen based on the Richmond Agitation Sedation Scale (RASS; n, -5 to +4). Scores from +2 to +4 will count as a positive screen for agitation	Preoperative baseline through postoperative day three afternoon
Secondary	Headache	Headache severity will be assessed via 10-centimeter visual analog scale (0-100 mm, with higher score indicating more severe headache)	Preoperative baseline through postoperative day three afternoon
Secondary	Cumulative Opioid Consumption	Postoperative opioid consumption, oral morphine equivalents (mg)	Day of surgery through postoperative day three afternoon