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

NCT ID: NCT05574400

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-20
• Study Completion Date: 2026-05-31

Brief 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.

Detailed 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.

Conditions

Postoperative Delirium; Postoperative Cognitive Dysfunction; Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Control

Prepared intravenous piggyback solution of 5 percent dextrose water at multiple postoperative time points over a 30-minute infusion period.

Group Type: PLACEBO_COMPARATOR

Dextrose Water

Intervention Type: DRUG

Dextrose 5% in water

Low-dose Caffeine

Prepared intravenous low-dose caffeine citrate (1.5 mg/kg) at multiple postoperative time points over a 30-minute infusion period.

Group Type: EXPERIMENTAL

Caffeine citrate

Intervention Type: DRUG

Low-dose caffeine citrate (1.5 mg/kg)

High-dose Caffeine

Prepared intravenous high-dose caffeine citrate (3 mg/kg) at multiple postoperative time points over a 30-minute infusion period.

Group Type: EXPERIMENTAL

Caffeine citrate

Intervention Type: DRUG

High-dose Caffeine citrate (3 mg/kg)

Interventions

Dextrose Water

Dextrose 5% in water

Intervention Type: DRUG

Caffeine citrate

Low-dose caffeine citrate (1.5 mg/kg)

Intervention Type: DRUG

Caffeine citrate

High-dose Caffeine citrate (3 mg/kg)

Intervention Type: DRUG

Eligibility Criteria

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. Active carcinoid syndrome

12. Severe audiovisual impairment

13. Non-English speaking

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Phillip Vlisides

Assistant Professor of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Phillip Vlisides, MD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor of Anesthesiology

Locations

Michigan Medicine

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Phillip Vlisides, MD

Role: CONTACT

pvliside@umich.edu

(734) 936-4280

Amy McKinney, MA

Role: CONTACT

adrongo@umich.edu

(734) 647-8129

Facility Contacts

Phillip Vlisides, MD

Role: primary

pvliside@med.umich.edu

734-936-4280

Amy McKinney, MA

Role: backup

adrongo@med.umich.edu

734-647-8129

References

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.

Reference Type: BACKGROUND

PMID: 33939649 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34987367 (View on PubMed)

Vlisides PE, Ragheb J, McKinney A, Mentz G, Runstadler N, Martinez S, Jewell E, Lee U, Vanini G, Schmitt EM, Inouye SK, Mashour GA. Caffeine, Postoperative Delirium And Change In Outcomes after Surgery (CAPACHINOS)-2: protocol for a randomised controlled trial. BMJ Open. 2023 May 15;13(5):e073945. doi: 10.1136/bmjopen-2023-073945.

Reference Type: DERIVED

PMID: 37188468 (View on PubMed)

Other Identifiers

R01AG075005

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HUM00218290

Identifier Type: -

Identifier Source: org_study_id