Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000579493
Ethics application status
Approved
Date submitted
9/05/2025
Date registered
4/06/2025
Date last updated
4/06/2025
Date data sharing statement initially provided
4/06/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
The NIKI-C Study - A study of plasma pharmacokinetics of nebulized ketamine in post cardiac surgery patients.
Scientific title
A study of plasma pharmacokinetics of nebulized ketamine in post cardiac surgery patients in intensive care unit: A phase 2 single site, prospective, interventional, open-label pharmacokinetic study.
Secondary ID [1] 314304 0
Nil
Universal Trial Number (UTN)
Trial acronym
NIKI-C Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-operative intensive care. 337252 0
Intensive Care Cardiac Surgery 337253 0
Condition category
Condition code
Anaesthesiology 333656 333656 0 0
Pain management
Cardiovascular 333968 333968 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single site study, evaluating the pharmacokinetics (PK) of a single dose of nebulized ketamine in post cardiac surgery patients in the intensive care unit (ICU). The study also aims to define the optimal dosing regimens to inform future clinical trials.

Design and setting:
A minimum 20 post-operative cardiac surgery patients in the ICU that meet the inclusion criteria and none of the exclusion criteria will be recruited. In addition to standard analgesia and sedation prescribed by the treating clinician, each patient will receive nebulized ketamine 0.75mg/kg ideal body weight (IBW).

Consent
Patients must be able to consent for themselves in order to be eligible for the study. Patients are admitted to the ICU in the later part of the day and extubated later in the evening. The day following surgery patients will be assessed for suitability. Eligible patients will be approached by the Principal Investigator. In consultation with the treating team patients will be assessed for competence prior to approaching for consent.

Intervention
All patients continue to receive standard of care analgesia (oral, intravenous or epidural) as prescribed by the treating team.
A vibrating mesh nebuliser with mouthpiece and exhalation filter will be used to administer the ketamine. The exhalation filter on the nebulizer expiratory port will eliminate the risk of environmental contamination for those present. patients will be shown the nebulizer and given detailed instructions and demonstration regarding the use.
For patients on low flow (FiO2 < 0.4) or no oxygen the bacterial filter applied to the exhalation port will reduce fugitive emissions.
For patients on high flow nasal cannula (FiO2 < 0.4) the vibrating mesh nebulizer will be inserted in the circuit on the dry side of the humidifier as per current practice. the patient will be requested to wear a surgical mask to cover their mouth and prevent fugitive emissions.
Ketamine 0.75mg/kg (based on IBW) rounded to the nearest 5kg will be instilled in the nebulizer chamber to make up to a total of 3mL volume. Nebulization will continue until there is no visible mist.

Biological Samples
8 blood samples (3mL each) will be collected into heparinised tubes over two hours (T=0, T+5, +10, +15, +30, +60, +90, +120 minutes) via an existing arterial or central line.
A urine creatinine will be performed from time dosing commences until the end of the two hour sampling period. A 1 mL aliquot of urine from the total sample will be retained to determine renal excretion of the study drug.

Monitoring Fidelity
The qualified research team who are familiar with the study protocol and procedure will be at the bedside throughout the sampling period and will be monitoring for study compliance as per protocol. Data collection is completed by the research team in real time to ensure accuracy and negate the chance of missed data points. A data collection sheet will be completed for all samples collected including time of collection. Nebulization start and stop time is recorded. Medication dose will be calculated and checked by 2 competent clinical personnel at least one of whom will be a study team member. The template medication order will be used to ensure accuracy and consistency across all patients. Clear instructions are provided in the bedside resources for the study team to use that outline sample collection procedure and handling. Study team are highly experienced in these kind of studies and understand the importance of timeliness, correct sample handing and processing and adherence to protocol.

A monitoring plan has been established for the study, including a Safety Monitoring Committee (SMC). Protocol adherence will be easily monitored s this is a single site study and the study team will be directly involved in each case. The study will be conducted in accordance with ethical principles consistent with the Declaration of Helsinki, and all relevant national and local guidelines on the ethical conduct of research. The Research team will include experienced research coordinators, intensive care specialists, all with Good Clinical practice (GCP) certification who will have oversight of all study activities and protocol adherence.

All data will be directly entered from the source into the REDCap electronic database. the database has the capacity to run validity checks and logic queries to minimise errors. the study monitor will perform 100% source data verification (SDV) for the first patient recruited and 100% SDV on all patients for informed consent in accordance with HREC approval, reportable adverse events as per protocol, clinical outcomes and protocol deviations.
Intervention code [1] 330918 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341242 0
Urine Creatine Clearance (CrCL)
Timepoint [1] 341242 0
A two hour urine CrCL will be collected on the day of sampling where commencement of sample is the start time of nebulization.
Primary outcome [2] 341241 0
To evaluate the plasma pharmacokinetics of single dose ketamine in post-operative cardiac surgery patients in the ICU.
Timepoint [2] 341241 0
Plasma samples will be collected over a two hour sampling window where T=0 is the commencement of nebulization of the study frug. A total of 8 samples will be collected. T0, T+5, +10, +15, +30, +60, +90, +120 minutes.
Secondary outcome [1] 446900 0
Safety
Timepoint [1] 446900 0
Monitoring for adverse events will occur during the study sampling period and up to 4 hours after end of study drug nebulisation.
Secondary outcome [2] 446903 0
Feasibility of a large randomized controlled trial to provide effective analgesia as an adjunct for conventional therapy for pain management in this patient population.
Timepoint [2] 446903 0
Pain monitoring 1. NPRS and RASS assessment at T=0 (baseline predosing), 30 min, 60 min, end of study (T=120 min 2 hour post nebulization). 2. Break through analgesia during the two hour sampling period post-nebulization.

Eligibility
Key inclusion criteria
Post-operative cardiac surgery patient in the intensive care unit willbe considered if they meet the following criteria:

1. Adult greater than or equal to 18 years
2. Has an arterial or central venous line insitu
3. Requiring analgesia as per treating team
4. Able to provide consent to participate
5. Able to inhale nebulized medications
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. suspected or known hypersensitivity to ketamine
2. already receiving ketamine for analgesia
3. severe chronic lung disease
4. systolic blood pressure less than 11 mmHg
5. high oxygen requirement FiO2 greater than or equal to 0.4
6. cardiac dysrhythmia
7. receiving renal replacement therapy
8. liver failure or Child-Pugh C liver cirrhosis
9. pregnant or lactating patients
10. history of significant mental health disorder or psychological distress as assessed by the PI that will impact consent and/or prevent participation in the study
11. delirium
12. previous enrolment in the NIKI-C study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size for the study is a minimum of 20 patients. The sample size is based on data from similar studies and will provide a power of 80% and is expected to obtain robust population PK [parameter predictions in this patient population, which demonstrates high PK variability.
Continuous variables will be assessed for normality and expressed as means ± SD or medians ± IQR and categorical variables will be expressed as proportions.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/07/2025
Actual
Date of last participant enrolment
Anticipated
30/12/2026
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 27847 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 44042 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 318825 0
University
Name [1] 318825 0
University of Queensland Research Fellowship
Country [1] 318825 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 321304 0
None
Name [1] 321304 0
Address [1] 321304 0
Country [1] 321304 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317442 0
Metro North Health Human Research Ethics Committee B
Ethics committee address [1] 317442 0
Ethics committee country [1] 317442 0
Australia
Date submitted for ethics approval [1] 317442 0
31/01/2024
Approval date [1] 317442 0
03/06/2024
Ethics approval number [1] 317442 0
HREC/2024/MNHB/105595

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 141042 0
Dr Kiran Shekar
Address 141042 0
Intensive Care Department, The Prince Charles Hospital, 627 Rode Road, Chermside. QLD 4032
Country 141042 0
Australia
Phone 141042 0
+61 7 3139 5922
Fax 141042 0
Email 141042 0
[email protected]
Contact person for public queries
Name 141043 0
Kiran Shekar
Address 141043 0
Intensive Care Department, The Prince Charles Hospital, 627 Rode Road, Chermside. QLD 4032
Country 141043 0
Australia
Phone 141043 0
+61 7 3139 5922
Fax 141043 0
Email 141043 0
[email protected]
Contact person for scientific queries
Name 141044 0
Jayesh Dhanani
Address 141044 0
ICU Research, Level 3 Ned Hanlon Building Butterfield Street Herston QLD 4029
Country 141044 0
Australia
Phone 141044 0
+61 7 3646 8897
Fax 141044 0
Email 141044 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


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.