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Postoperative DeliriumPhase 2NCT05574400

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

A Phase 2 study testing Dextrose Water and Caffeine citrate in people with Postoperative Delirium and Postoperative Cognitive Dysfunction, run by University of Michigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 70 years and older
What is being tested?
Dextrose Water and Caffeine citrate
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
250 participants
Where
1 siteUnited States
Study dates
20 Feb 2023to 20 May 2026
Phase
Phase 2
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 70 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Michigan Medicine

    Ann Arbor, Michigan, 48109

Other trials in United States

About this study

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.

Read the 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.

Being tested
Dextrose Water, Caffeine citrate
Keywords
Postoperative Delirium, Neurocognitive Disorders, Mild Cognitive Impairment, Alzheimer's Disease
Medical subject headings
Emergence Delirium, Postoperative Cognitive Complications, Cognitive Dysfunction, Neurocognitive Disorders, Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dextrose WaterDrug

    Dextrose 5% in water

  • Caffeine citrateDrug

    Low-dose caffeine citrate (1.5 mg/kg)

  • Caffeine citrateDrug

    High-dose Caffeine citrate (3 mg/kg)

Study groups in NCT05574400
Study groupRoleWhat they receive
ControlPlacebo comparatorPrepared intravenous piggyback solution of 5 percent dextrose water at multiple postoperative time points over a 30-minute infusion period.
Receives: Drug: Dextrose Water
Low-dose CaffeineExperimentalPrepared intravenous low-dose caffeine citrate (1.5 mg/kg) at multiple postoperative time points over a 30-minute infusion period.
Receives: Drug: Caffeine citrate
High-dose CaffeineExperimentalPrepared intravenous high-dose caffeine citrate (3 mg/kg) at multiple postoperative time points over a 30-minute infusion period.
Receives: Drug: Caffeine citrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Day of surgery through afternoon of postoperative day three

Secondary outcomes (7)

  1. 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)

    Measured: Day of surgery through afternoon of postoperative day three

  2. Delirium Duration

    The cumulative number of days (n) with a positive delirium screen will be calculated for all participants

    Measured: Day of surgery through afternoon of postoperative day three

  3. 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)

    Measured: Preoperative baseline through postoperative day three afternoon

  4. 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.

    Measured: Preoperative baseline through postoperative day three afternoon

  5. 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

    Measured: Preoperative baseline through postoperative day three afternoon

  6. Headache

    Headache severity will be assessed via 10-centimeter visual analog scale (0-100 mm, with higher score indicating more severe headache)

    Measured: Preoperative baseline through postoperative day three afternoon

  7. Cumulative Opioid Consumption

    Postoperative opioid consumption, oral morphine equivalents (mg)

    Measured: Day of surgery through postoperative day three afternoon

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2022
  2. Study start20 Feb 2023
  3. Primary completion16 Apr 2026
  4. Study completion20 May 2026

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This will be a three-arm parallel trial.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
250 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05574400
Sponsor's protocol ID
HUM00218290
Other IDs
R01AG075005
Status last verified
Jul 2026
First submitted
6 Oct 2022
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Clinical and electroencephalographic data will be preserved and made available for sharing. Data will be saved in various formats, such as comma-separated values (CSV), open document format (ODF), and European Data Format (EDF) for waveform data. Software programs designed to accommodate electroencephalographic waveform data (e.g., MATLAB) will be required for data access and analysis. Specific software and coding recommendations can be made available upon data sharing request. Any data not permitted to be shared, as specified in written informed consent documents, will be withheld. Likewise, no data will be shared that may compromise the safety or privacy of participants, and no data will be shared that would violate local, state, or federal laws or policies (including the Health Insurance Portability and Accountability Act). All data will be de-identified.

Publications

  • 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.

    PubMed 33939649

  • 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.

    PubMed 34987367

  • 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.

    PubMed 37188468

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dextrose Water and Caffeine citrate in people with Postoperative Delirium and Postoperative Cognitive Dysfunction, run by University of Michigan at 1 site in United States.

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 3 inclusion and 13 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 16 Jul 2026. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Delirium (time frame: Day of surgery through afternoon of postoperative day three). 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 NCT05574400, which also lists 3 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 16 Jul 2026.

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