- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05232734
CaffeinICU Study - A Pilot Study on the Efficacy of Oral Caffeine in Reducing the Duration of Mechanical Ventilation (CaffeinICU)
CaffeinICU Study - A Randomized Controlled Multi-centre Pilot Study, on the Efficacy of Oral Caffeine, in Reducing the Duration of Mechanical Ventilation in Critically Ill Adult Patients
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Objective:
The primary objective is to investigate the efficacy of oral caffeine in shortening the duration of mechanical ventilation among adult patients. The secondary objective is to investigate its relation to 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
Hypothesis:
Oral caffeine is effective as a central nervous system stimulant among adult patients with depressed GCS.
Proposed Trial Design:
We propose a pilot multi-center, double blind, randomized controlled trial of 30 patients with depressed GCS, randomly assigned to receive oral caffeine or placebo.
Planned Trial Interventions:
Patients will be allocated to 2 groups (15 patients each)
- Oral caffeine group: patient 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.
- Control group: patient will receive syrup BP (placebo, same diluent that is used for preparation of caffeine solution) through their feeding tube, packed and supplied in amber glass bottle by pharmacy laboratory.
Oral caffeine or placebo will be initiated within 24 hours of randomization. Study intervention will be administered to patients for 3 days after recruitment or until ICU discharge, whichever comes first.
The study intervention (oral caffeine) or placebo will be administered in addition to usual standards of care for ICU patients .
Subject Consent and Randomization:
Consent will be obtained from patient's Legally Appointed Representative(LAR) if available, or the next of kin within 72 hours following inclusion and exclusion criteria screening.
The randomization system will use a computer generated randomization schedule allocating patients 1:1 to either caffeine or matching placebo by the method of permuted blocks of random undisclosed size within strata.
Allocation will be random and blinded to everyone except the laboratory pharmacists who will be preparing and labelling study samples. As patients will be fed via feeding tube, they will not be able to differentiate the taste of the product.
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Singapore, Singapore, 169608
- Recruiting
- Singapore General Hospital
-
Contact:
- Sharon GK Ong, MBBS
- Phone Number: 81253571
- Email: sharon.ong.g.k@singhealth.com.sg
-
Contact:
- Chuan Poh Lim
- Phone Number: 97242203
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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,
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Oral caffeine group
Patients in this arm will receive treatment with oral 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.
Other Names:
|
Placebo Comparator: Control group
Patients in this group will receive syrup BP (placebo)
|
Syrup BP 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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ICU mortality
Time Frame: From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
|
Mortality in the ICU (yes or no)
|
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
|
Mortality within 30 days (yes or no)
|
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
|
Length of ICU stay in days
|
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
|
Blood pressure in mmHg
|
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
|
Heart rate in beats per minute
|
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
|
Incidence of arrhythmia reported (yes or no)
|
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
|
Glasgow coma scale
|
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
|
Need for re-intubation following an extubation (yes or no)
|
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
|
Terminal extubation in the ICU (yes or no)
|
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
|
Need for tracheostomy (yes or no)
|
From the start of study drug with follow up period of 30 days or until hospital discharge, whichever earlier
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Central Nervous System Diseases
- Nervous System Diseases
- Depression
- Brain Diseases
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Purinergic Antagonists
- Purinergic Agents
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Central Nervous System Stimulants
- Caffeine
- Caffeine citrate
Other Study ID Numbers
- 2021/2556
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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