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

NCT05574400 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HUM00218290R01AG075005
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Delirium; Postoperative Cognitive Dysfunction; Mild Cognitive Impairment

Keywords

Postoperative Delirium; Neurocognitive Disorders; Mild Cognitive Impairment; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Delirium

  Any positive delirium screen (yes/no) as determined by the long-form Confusion Assessment Method (CAM), and supplemented by a validated daily chart review method.

  Day of surgery through afternoon of postoperative day three

Secondary Outcomes (7)

• Delirium Severity

  Day of surgery through afternoon of postoperative day three

• Delirium Duration

  Day of surgery through afternoon of postoperative day three

• Patient-Reported Quality of Recovery

  Preoperative baseline through postoperative day three afternoon

• Sedation

  Preoperative baseline through postoperative day three afternoon

• Agitation

  Preoperative baseline through postoperative day three afternoon

Other Outcomes (6)

• Anesthetic Emergence

  Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes

• Pulmonary Complications

  From extubation until end of postanesthesia care unit stay

• Hospital Length of Stay

  Morning of surgery until day of hospital discharge, up to 30 days

Study Arms (3)

Control

PLACEBO COMPARATOR

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

Drug: Dextrose Water

Low-dose Caffeine

EXPERIMENTAL

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

Drug: Caffeine citrate

High-dose Caffeine

EXPERIMENTAL

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

Drug: Caffeine citrate

Interventions

Dextrose Water DRUG

Dextrose 5% in water

Control

Caffeine citrate DRUG

Low-dose caffeine citrate (1.5 mg/kg)

Low-dose Caffeine

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Provision of signed and dated informed consent form.

You may not qualify if:

• Emergency surgery
• Outpatient surgery
• Severe cognitive impairment precluding the capacity for informed consent
• Seizure disorder history
• Intolerance or allergy to caffeine (based on subjective reporting or objective documentation)
• Weight \>130 kg (as a 3 mg/kg dose would approach the upper limit of daily intake recommended by the FDA)
• Enrollment in conflicting research study
• Patients in acute liver failure
• Acute kidney injury preoperatively
• Diagnosis of pheochromocytoma
• Active carcinoid syndrome
• Severe audiovisual impairment
• Non-English speaking

Sponsors & Collaborators

• University of Michigan: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (3)

• 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.

  PMID: 33939649 BACKGROUND

• 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.

  PMID: 34987367 BACKGROUND

• 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.

  PMID: 37188468 DERIVED

MeSH Terms

Conditions

Emergence Delirium; Postoperative Cognitive Complications; Cognitive Dysfunction; Neurocognitive Disorders; Alzheimer Disease

Interventions

caffeine citrate

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Mental Disorders; Cognition Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Phillip Vlisides, MD

  Assistant Professor of Anesthesiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be a single-center, quadruple-blinded, randomized control trial at Michigan Medicine
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology

Model Details: This will be a three-arm parallel trial.

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 10, 2022
• Study Start: February 20, 2023
• Primary Completion: April 16, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Scientific data will be made available after primary trial manuscripts (for both clinical and electroencephalographic data) are accepted for publication. Data will be made available for as long as possible in compliance with National Institutes of Health and University of Michigan policies.
• Access Criteria: Data will be shared upon execution of Data Use Agreements in compliance with University of Michigan policies and procedures. Interested researchers will need to contact the study PI (Dr. Vlisides) for obtaining data via Data Use Agreement. All data will be shared upon reasonable request after primary trial manuscripts are published.

Locations

US (1)