Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001633875p
Ethics application status
Submitted, not yet approved
Date submitted
26/10/2021
Date registered
29/11/2021
Date last updated
2/06/2023
Date data sharing statement initially provided
29/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
DeCaf-Me: Can delirium be prevented with caffeine and melatonin? A randomised, placebo-controlled trial
Scientific title
DeCaf-Me: Can delirium be prevented with caffeine and melatonin? A randomised, placebo-controlled trial
Secondary ID [1] 305657 0
none
Universal Trial Number (UTN)
Trial acronym
DeCaf-Me
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Delirium 324125 0
Post-operative pain 324359 0
Vascular surgery 324360 0
Spinal surgery 324361 0
Condition category
Condition code
Neurological 321604 321604 0 0
Other neurological disorders
Anaesthesiology 321605 321605 0 0
Pain management
Surgery 321843 321843 0 0
Other surgery
Cardiovascular 321844 321844 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will have the following three intervention arms:
1) Oral 100 mg Caffeine (NoDoz) twice daily at 0700 and 1400 and oral Melatonin (circadian) 4mg once per day at 2000 on post operative days 1 and 2
2) Oral 100 mg Caffeine twice daily at 0700 and 1400 on post-operative days 1 and 2
3) Oral 4mg Melatonin once daily at 2000 on post-operative days 1 and 2
Intervention code [1] 322052 0
Treatment: Drugs
Intervention code [2] 322227 0
Prevention
Comparator / control treatment
Control group =No Intervention
Stand post-operative care will continue including regular patient medications, analgesia, anti-emetics and medications to maintain haemodynamic stability as required. There are no restrictions/limitations to post-operative care and the treating medical team will provide ongoing post-operative care at their discretion and as per their standard care.
Control group
Active

Outcomes
Primary outcome [1] 329371 0
Delirium severity assessed using the Delirium Rating Scale- Revised- 98 (DRS-R-98)
Timepoint [1] 329371 0
Assessed twice on post-operative day 1 (morning from 0600-1000 and afternoon 1400-1800)
Primary outcome [2] 329605 0
Delirium severity assessed using Richmond Agitation and Sedation Scale (RASS)
Timepoint [2] 329605 0
Assessed twice on post-operative day 1 (morning from 0600-1000 and afternoon from 1400-1800)
Primary outcome [3] 329606 0
Delirium severity assessed using the Confusion Assessment Method - Severity (CAM-S)
Timepoint [3] 329606 0
Assessed twice on post-operative day 1 (morning from 0600-1000 and afternoon from 1400-1800)
Secondary outcome [1] 402378 0
Instances and severity of post-operative delirium using DRS-R-98
Timepoint [1] 402378 0
Assessed twice on post-operative days 1, 2 and 3 (morning assessment between 0600-1000 and afternoon between 1400-1800)
Secondary outcome [2] 403150 0
Differences in Electrocephalogram (EEG) power from 0.5-6Hz
Timepoint [2] 403150 0
Measured intra-operatively and on post-operative day 1
Secondary outcome [3] 403151 0
Instance and severity of delirium assessed using 3D CAM-S
Timepoint [3] 403151 0
Assessed twice daily on post-operative days 1, 2 and 3 (morning assessment between 0600-1000 and afternoon between 1400-1800)
Secondary outcome [4] 403152 0
Changes in Richmond Agitation and Sedation Score (RASS)
Timepoint [4] 403152 0
Assessed twice daily on post-operative days 1-3 (morning assessment between 0600-1000 and afternoon between 1400-1800)
Secondary outcome [5] 403153 0
Post-operative pain scores using the visual analogue scale for pain as documented by nursing staff
Timepoint [5] 403153 0
Assessed once daily on post-operative days 1-3 (average pain score will be calculated)
Secondary outcome [6] 403156 0
Safety of using post-operative caffeine and melatonin assessed through documentation of adverse events/serious adverse events (specifically cardiovascular arrhythmias or myocardial events)
Timepoint [6] 403156 0
Assessed on post-operative days 1-7 through review of electronic medical records/patient follow up

Eligibility
Key inclusion criteria
Patients undergoing vascular or spinal surgery
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Non-english speaking
Participants who may have received an investigational new drug within the last 7 days/weeks.
Participants with a history of a psychological illness or other conditions which may interfere with their ability to understand the study requirements such as preexisting dementia.
Participants with prior known intolerance/allergy to caffeine
Undergoing cardiac or intracranial neurosurgery
Known history of intolerance of caffeine or melatonin

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation by computer- RedCap program supplied by SLHD
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software. As above through RedCap supplied by SLHD.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This pilot study is powered for a 50% reduction in the mean severity of delirium (Delirium rating scale 98 of 12 vs. 6, standard deviation of 7), p<0.025 for two endpoints.

The primary outcome, the DRS-98 will be analyzed by Mann-Whitney or t-test depending on distribution.
The incidence of resolution of delirium (on 3D-CAM), will be analysed by Fischer’s exact test.
The RASS will be analyzed by Mann-Whitney or t-test depending on distribution.
EEG analysis will be conducted by pwelch calculation of power bands and Mann-Whitney or t-test depending on distribution.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2023
Actual
Date of last participant enrolment
Anticipated
4/08/2025
Actual
Date of last data collection
Anticipated
3/08/2026
Actual
Sample size
Target
57
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20950 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 35767 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 310016 0
Hospital
Name [1] 310016 0
Department of Anaesthetics- Royal Prince Alfred Hospital
Country [1] 310016 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Royal Prince Alfred Hospital
50 Missenden Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 311080 0
None
Name [1] 311080 0
Address [1] 311080 0
Country [1] 311080 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 309723 0
Sydney Local Health District (RPAH Zone)
Ethics committee address [1] 309723 0
Sydney Local Health District
Level 11, KGV Building Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 309723 0
Australia
Date submitted for ethics approval [1] 309723 0
23/11/2021
Approval date [1] 309723 0
Ethics approval number [1] 309723 0

Summary
Brief summary
DeCaf-Me: Prevent Delirium with Caffeine or Melatonin is a open label cross over factorial randomised controlled trial that is aiming to recruit 57 spinal or vascular participants over the age of 65 at Royal Prince Alfred Hospital. Participants will be recruited via the Department of Anaesthetics in the pre-admission clinic. They will be assessed for eligibility and risk at this time, informed consent will be done pre-operatively.

Participants will be randomised to one of four arms - 1)100 mg caffeine at 7am and 2pm, 4 mg melatonin at 8pm, 2)100mg caffeine at 7am and 2pm, 3)4mg melatonin at 8pm or 4)no intervention.

Primary outcomes are incidence of post-operative delirium on day 1 and secondary outcomes are Richmond Agitation and Sedation Score, differences in EEG power from 0.5-0.6Hz, changes in incidence of delirium, post-operative pain and opioid use. Patients will be monitored intraoperatively via BIS monitoring/EEG and on post operative days 1-3 receive delirium assessments on the ward/ICU. Additionally an EEG will be preformed on post-operative day 1 and a 10mL blood sample will be collected for biomarker analysis during standard blood collection intra-operatively and on post-operative day 1. Participants will be finished on post-operative day 7 after completing a cognitive assessment in person or over the phone.

The rationale of this study is that the use of post-operative caffeine could have an effect on inflammation that could effect post-operative delirium severity and the consequential slowing of electroencephalogram readings. Additionally the use of caffeine and melatonin to help maintain circadian rhythms could help promote more restful sleep and reinforce normal sleep patterns which can reduce instances of post-operative delirium.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115170 0
Prof Robert Sanders
Address 115170 0
Department of Anaesthetics
Royal Prince Alfred Hospital
50 Missenden Road
Level 4, BLDG 89
Camperdown NSW 2050
Country 115170 0
Australia
Phone 115170 0
+61 02 9515 8564
Fax 115170 0
Email 115170 0
[email protected]
Contact person for public queries
Name 115171 0
Miss Kaitlin Kramer
Address 115171 0
Department of Anaesthetics
Royal Prince Alfred Hospital
50 Missenden Road
Level 4, BLDG 89
Camperdown NSW 2050
Country 115171 0
Australia
Phone 115171 0
+61 2 9515 8789
Fax 115171 0
Email 115171 0
[email protected]
Contact person for scientific queries
Name 115172 0
Prof Robert Sanders
Address 115172 0
Department of Anaesthetics
Royal Prince Alfred Hospital
50 Missenden Road
Level 4, BLDG 89
Camperdown NSW 2050
Country 115172 0
Australia
Phone 115172 0
+61 02 9515 8564
Fax 115172 0
Email 115172 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13792Study protocol    383028-(Uploaded-23-05-2022-11-06-53)-Study-related document.pdf
13793Informed consent form    383028-(Uploaded-23-05-2022-11-07-33)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.