Depressed GCSPhase 2CaffeinICUNCT05232734
CaffeinICU Study - A Study on Oral Caffeine in ICU Patients With Coma
A Phase 2 study testing Caffeine Citrate 20 MG/ML Oral Solution in people with Depressed GCS, run by Singapore General Hospital at 1 site in Singapore.
Trial summary
Background: Depressed Glasgow Coma Scale (GCS) is common among critically ill patient s in the intensive care unit (ICU). It is one of the main reasons that hampers liberation from mechanical ventilation among ICU patients. Caffeine is commonly used in neonates for the treatment of apnea of prematurity. Read more about this study
- Who is it for?
- Ages 21 to 130 years
- Conditions the study is for
- Depressed GCS
- What is being tested?
- Caffeine Citrate 20 MG/ML Oral Solution
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSingapore
- Study dates
- 24 Nov 2022to 31 Dec 2025
- 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 21 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (≥ 21 years old),
- Patients with encephalopathy (GCS ≤ 8) limiting extubation, where encephalopathy is deemed by clinician to be unresponsive to treatment or not eligible for treatment to reverse the encephalopathy (eg. transplantation) or if no treatment exists, and
- Patients who are not planned for any surgical procedures within 24 hours
- Patients who are not on sedative agents for at least 24 hours (exception for low dose fentanyl of up to 30mcg/h and dexmedetomidine of up to 0.5mcg/kg/h for analgesia/sedation/tube tolerance)
- For patients with primary CNS lesions, neurologist or neurosurgeon approval will be obtained prior to recruitment.
Who cannot join
- Known allergy or adverse reactions from caffeine,
- Pregnant women,
- Breast-feeding women,
- Patients with uncontrolled cardiac arrhythmias,
- Patients with uncontrolled hypertension,
- Patients with hyperactive delirium,
Show all 11Show fewer
- Patients with chronic kidney disease (CKD, any stage) who received midazolam or morphine infusion during their ICU stay,
- Patients who received barbiturate coma,
- Patients who are on theophylline, aminophylline or psychotropic agents at the point of screening for recruitment,
- Patients with feed intolerant, short bowel syndrome, or
- Patients with active seizures
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CaffeinICU Study - A Multi-centre Pilot Study to Examine the Safety and Feasibility of Oral Caffeine in Critically Ill Adult Patients With Low Glasgow Coma Scale Score.
Background:
Depressed Glasgow Coma Scale (GCS) is common among critically ill patient s in the intensive care unit (ICU). It is one of the main reasons that hampers liberation from mechanical ventilation among ICU patients. Caffeine is commonly used in neonates for the treatment of apnea of prematurity. However, its efficacy has not been established in adult population.
Read more
Objective:
To find out the efficacy of oral caffeine in shortening duration of mechanical ventilation among adult patients.
Hypothesis:
Oral caffeine is effective as a central nervous system stimulant among adult patients with depressed GCS.
Study design:
Multi-center, randomised, double blind, placebo controlled clinical trial
Population:
Adult patients (≥ 21 years old) with GCS ≤ 8 from any causes (excluding surgically reversible causes) requiring continuation of mechanical ventilation, whom acute medical issues are stable or has resolved but not suitable for extubation solely due to depressed GCS, not planned for any surgical procedures within 24 hours and not on sedative agents for at least 24 hours, will be included in this study. For patients with primary Central Nervous System (CN lesions, neurologist or neurosurgeon approval will be obtained prior to recruitment. The exclusion criteria include known allergy or adverse reactions from caffeine, pregnant women, breast-feeding women, uncontrolled cardiac arrhythmias, uncontrolled hypertension, hyperactive delirium, patients with chronic kidney disease (CKD, any stage) who received midazolam or morphine infusion, patients who received barbiturate coma, patients who are on theophylline, aminophylline or psychotropic agents at the point of screening for recruitment, patients with feed intolerant, short bowel syndrome and active seizures.
Intervention:
Oral caffeine citrate 5mg/kg/dose twice a day (8am, 2pm) vs placebo
Outcomes:
Primary - Duration of mechanical ventilation Secondary - ICU mortality, 30-days mortality, ICU length of stay, blood pressure, heart rate, incidence of arrhythmia, GCS, incidence of re-intubation and need for tracheostomy
Read the detailed description
Depressed Glasgow Coma Scale (GCS) is common among critically ill patients in the intensive care unit (ICU). It is one of the main reasons that hampers liberation from mechanical ventilation among ICU patients. Current management of this disorder focuses mainly on supportive care and treatment of the underlying disease. Directed therapies targeting neurochemical and neurotransmitter pathways are not currently available and it represents an important area of research. Caffeine is commonly used in neonates for the treatment of apnea of prematurity. It is a CNS stimulant that stimulates central respiratory drive, increases medullary respiratory center sensitivity to carbon dioxide and improves diaphragmatic contractility. However, its efficacy has not been established in adult population.
Hypothesis:
- Oral caffeine is safe for use for adult ICU patients with depressed GCS at the selected dose.
- It is feasible to recruit the stipulated study population from SGH and SKH within the time frame of the study.
Objective:
The primary objectives of the study are:
- To study the safety of oral caffeine among critically ill adult patients. Specifically, the investigators will observe for changes in the blood pressure and heart rate, as well as any incidence of arrthythmia among critically ill adult patients administered with oral caffeine
- To study the feasibility of the study. Specifically, the investigators will observe and examine factors and challenges (such as from the inclusion/exclusion criteria, caregiver's willingness to participate) that influence recruitment
- To estimate the duration of mechanical ventilation with the use of oral caffeine (dose: 5mg/kg/dose twice daily) in adult patients who are critically ill.
The secondary objectives are:
(To describe the ICU mortality, 30-days mortality, ICU length of stay, GCS, incidence of re-intubation, incidence of terminal extubation and need for tracheostomy among critically ill adult patients administered with oral caffeine
Proposed Trial Design:
The investigators propose a pilot multi-center, single arm trial of 10 patients with depressed GCS, assigned to receive oral caffeine. 10 subjects from SGH and SKH who are on mechanical ventilation with depressed GCS will be recruited into this study. No randomisation or blinding will be carried out in this study.
Planned Trial Interventions:
Participants will receive oral caffeine through their feeding tube, 5mg/kg/dose twice daily. Oral caffeine solution (colorless and odorless) will be prepared by pharmacy laboratory and supplied in amber glass bottle. Potential drug-drug interaction with oral caffeine will be monitored throughout the study period:
- CYP1A2 enzyme inhibitors and inducers to be taken with caution/prohibited
- CYP1A2 substrates to be taken with caution/prohibited
Screening Visits and Procedures:
Study subjects will be identified through referral by the attending ICU medical team or weekly patient screening. Potential subjects will be reviewed by one of the study team members for recruitment eligibility, according to the study inclusion and exclusion criteria. Consent will be obtained from patient's Legally Appointed Representative(LAR) if available, or the next of kin within 72 hours.
Duration of follow up:
Patient clinical status will be monitored on daily basis until 30 days after recruitment or discharge from hospital, whichever earlier.
Data collection:
Data collection will be done prospectively. All parameters collected are part of standard of care, no additional test required for the purpose of this study. Study feasibility data will be collected from screening and recruitment logs.
- Conditions
- Depressed GCS
- Being tested
- Caffeine Citrate 20 MG/ML Oral Solution
- Keywords
- Caffeine, Depressed GCS, Mechanical Ventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine Citrate 20 MG/ML Oral SolutionDrug
Also called Caffeine
Caffeine syrup will be prepared by pharmacy laboratory and kept refrigerated (2-8C), to be used within 1 month from the date of preparation by pharmacy laboratory.
| Study group | Role | What they receive |
|---|---|---|
| Oral caffeine group | Experimental | Patients in this arm will receive treatment with oral caffeine Receives: Drug: Caffeine Citrate 20 MG/ML Oral Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of mechanical ventilation
Duration of mechanical ventilation in days
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Secondary outcomes (10)
ICU mortality
Mortality in the ICU (yes or no)
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
30-days mortality
Mortality within 30 days (yes or no)
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
ICU length of stay
Length of ICU stay in days
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Blood pressure
Blood pressure in mmHg
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Heart rate
Heart rate in beats per minute
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Incidence of arrhythmia
Incidence of arrhythmia reported (yes or no)
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
GCS
Glasgow coma scale
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Incidence of re-intubation
Need for re-intubation following an extubation (yes or no)
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Incidence of terminal extubation
Terminal extubation in the ICU (yes or no)
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Need for tracheostomy
Need for tracheostomy (yes or no)
Measured: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2022
- Study start24 Nov 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Why it stopped: Study amendment done in view of low recruitment numbers. Updated HSA approved study protocol awaiting IRB approval before study re-commences
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depressed GCSStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Multi-center pilot observational single-arm clinical feasibility trial
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Sengkang General Hospital
- Responsible party
- Sponsor
- Investigators
- Sharon GK Ong, Principal investigator, A/Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05232734
- Sponsor's protocol ID
- 2021/2556
- Acronym
- CaffeinICU
- Status last verified
- Jun 2024
- First submitted
- 13 Jan 2022
- Last updated
- 27 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bright M, Raman V, Laupland KB. Use of therapeutic caffeine in acute care postoperative and critical care settings: a scoping review. BMC Anesthesiol. 2021 Mar 31;21(1):100. doi: 10.1186/s12871-021-01320-x.
PubMed 33789583
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CaffeinICU Study - A Multi-centre Pilot Study to Examine the Safety and Feasibility of Oral Caffeine in Critically Ill Adult Patients With Low Glasgow Coma Scale Score.
- ClinicalTrials.gov ID
- NCT05232734
- Acronym / sponsor ID
- CaffeinICU / 2021/2556
- Conditions
- Depressed GCS
- Keywords
- Caffeine, Depressed GCS, Mechanical Ventilation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Study amendment done in view of low recruitment numbers. Updated HSA approved study protocol awaiting IRB approval before study re-commences
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- Sengkang General Hospital
- Study start
- 24 Nov 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 10 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Depressed Glasgow Coma Scale (GCS) is common among critically ill patient s in the intensive care unit (ICU). It is one of the main reasons that hampers liberation from mechanical ventilation among ICU patients. Caffeine is commonly used in neonates for the treatment of apnea of prematurity. However, its efficacy has not been established in adult population.
Objective:
To find out the efficacy of oral caffeine in shortening duration of mechanical ventilation among adult patients.
Hypothesis:
Oral caffeine is effective as a central nervous system stimulant among adult patients with depressed GCS.
Study design:
Multi-center, randomised, double blind, placebo controlled clinical trial
Population:
Adult patients (≥ 21 years old) with GCS ≤ 8 from any causes (excluding surgically reversible causes) requiring continuation of mechanical ventilation, whom acute medical issues are stable or has resolved but not suitable for extubation solely due to depressed GCS, not planned for any surgical procedures within 24 hours and not on sedative agents for at least 24 hours, will be included in this study. For patients with primary Central Nervous System (CN lesions, neurologist or neurosurgeon approval will be obtained prior to recruitment. The exclusion criteria include known allergy or adverse reactions from caffeine, pregnant women, breast-feeding women, uncontrolled cardiac arrhythmias, uncontrolled hypertension, hyperactive delirium, patients with chronic kidney disease (CKD, any stage) who received midazolam or morphine infusion, patients who received barbiturate coma, patients who are on theophylline, aminophylline or psychotropic agents at the point of screening for recruitment, patients with feed intolerant, short bowel syndrome and active seizures.
Intervention:
Oral caffeine citrate 5mg/kg/dose twice a day (8am, 2pm) vs placebo
Outcomes:
Primary - Duration of mechanical ventilation Secondary - ICU mortality, 30-days mortality, ICU length of stay, blood pressure, heart rate, incidence of arrhythmia, GCS, incidence of re-intubation and need for tracheostomy
Detailed description
Depressed Glasgow Coma Scale (GCS) is common among critically ill patients in the intensive care unit (ICU). It is one of the main reasons that hampers liberation from mechanical ventilation among ICU patients. Current management of this disorder focuses mainly on supportive care and treatment of the underlying disease. Directed therapies targeting neurochemical and neurotransmitter pathways are not currently available and it represents an important area of research. Caffeine is commonly used in neonates for the treatment of apnea of prematurity. It is a CNS stimulant that stimulates central respiratory drive, increases medullary respiratory center sensitivity to carbon dioxide and improves diaphragmatic contractility. However, its efficacy has not been established in adult population.
Hypothesis:
- Oral caffeine is safe for use for adult ICU patients with depressed GCS at the selected dose.
- It is feasible to recruit the stipulated study population from SGH and SKH within the time frame of the study.
Objective:
The primary objectives of the study are:
- To study the safety of oral caffeine among critically ill adult patients. Specifically, the investigators will observe for changes in the blood pressure and heart rate, as well as any incidence of arrthythmia among critically ill adult patients administered with oral caffeine
- To study the feasibility of the study. Specifically, the investigators will observe and examine factors and challenges (such as from the inclusion/exclusion criteria, caregiver's willingness to participate) that influence recruitment
- To estimate the duration of mechanical ventilation with the use of oral caffeine (dose: 5mg/kg/dose twice daily) in adult patients who are critically ill.
The secondary objectives are:
(To describe the ICU mortality, 30-days mortality, ICU length of stay, GCS, incidence of re-intubation, incidence of terminal extubation and need for tracheostomy among critically ill adult patients administered with oral caffeine
Proposed Trial Design:
The investigators propose a pilot multi-center, single arm trial of 10 patients with depressed GCS, assigned to receive oral caffeine. 10 subjects from SGH and SKH who are on mechanical ventilation with depressed GCS will be recruited into this study. No randomisation or blinding will be carried out in this study.
Planned Trial Interventions:
Participants will receive oral caffeine through their feeding tube, 5mg/kg/dose twice daily. Oral caffeine solution (colorless and odorless) will be prepared by pharmacy laboratory and supplied in amber glass bottle. Potential drug-drug interaction with oral caffeine will be monitored throughout the study period:
- CYP1A2 enzyme inhibitors and inducers to be taken with caution/prohibited
- CYP1A2 substrates to be taken with caution/prohibited
Screening Visits and Procedures:
Study subjects will be identified through referral by the attending ICU medical team or weekly patient screening. Potential subjects will be reviewed by one of the study team members for recruitment eligibility, according to the study inclusion and exclusion criteria. Consent will be obtained from patient's Legally Appointed Representative(LAR) if available, or the next of kin within 72 hours.
Duration of follow up:
Patient clinical status will be monitored on daily basis until 30 days after recruitment or discharge from hospital, whichever earlier.
Data collection:
Data collection will be done prospectively. All parameters collected are part of standard of care, no additional test required for the purpose of this study. Study feasibility data will be collected from screening and recruitment logs.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Multi-center pilot observational single-arm clinical feasibility trial
| Arm | Type | Receives |
|---|---|---|
| Oral caffeine group | Experimental | Drug: Caffeine Citrate 20 MG/ML Oral SolutionPatients in this arm will receive treatment with oral caffeine |
Who may qualify
- Ages
- 21 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients (≥ 21 years old),
- Patients with encephalopathy (GCS ≤ 8) limiting extubation, where encephalopathy is deemed by clinician to be unresponsive to treatment or not eligible for treatment to reverse the encephalopathy (eg. transplantation) or if no treatment exists, and
- Patients who are not planned for any surgical procedures within 24 hours
- Patients who are not on sedative agents for at least 24 hours (exception for low dose fentanyl of up to 30mcg/h and dexmedetomidine of up to 0.5mcg/kg/h for analgesia/sedation/tube tolerance)
Key exclusion criteria (11 listed)
- Known allergy or adverse reactions from caffeine,
- Pregnant women,
- Breast-feeding women,
- Patients with uncontrolled cardiac arrhythmias,
- Patients with uncontrolled hypertension,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine Citrate 20 MG/ML Oral SolutionAlso: CaffeineCaffeine syrup will be prepared by pharmacy laboratory and kept refrigerated (2-8C), to be used within 1 month from the date of preparation by pharmacy laboratory. | Drug | Oral caffeine group |
Primary outcome
Duration of mechanical ventilation
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Duration of mechanical ventilation in days
10 secondary outcomes
ICU mortality
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
30-days mortality
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
ICU length of stay
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Blood pressure
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Heart rate
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Incidence of arrhythmia
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
GCS
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Incidence of re-intubation
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Incidence of terminal extubation
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Need for tracheostomy
Time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2024.
- Background: PubMed 33789583Bright M, Raman V, Laupland KB. Use of therapeutic caffeine in acute care postoperative and critical care settings: a scoping review. BMC Anesthesiol. 2021 Mar 31;21(1):100. doi: 10.1186/s12871-021-01320-x.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharon GK Ong principal investigator
A/Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Caffeine Citrate 20 MG/ML Oral Solution in people with Depressed GCS, run by Singapore General Hospital at 1 site in Singapore.
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 5 inclusion and 11 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: paused, as of the sponsor's last update on 27 Jun 2024. 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 Singapore. 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. 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?
Results are not available in the source record.
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?
Duration of mechanical ventilation (time frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier). 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 NCT05232734, which also lists 1 linked publication.
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 27 Jun 2024.