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Trial registered on ANZCTR


Registration number
ACTRN12625000171415
Ethics application status
Approved
Date submitted
20/11/2024
Date registered
13/02/2025
Date last updated
13/02/2025
Date data sharing statement initially provided
13/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
The NIKI-PT Study - A study of plasma pharmacokinetics of nebulized ketamine in post-operative and trauma patients.
Scientific title
A study of plasma pharmacokinetics of nebulized ketamine in post-operative and trauma patients in intensive care unit: A phase 2, single site, prospective, interventional, open-label pharmakinetic study,
Secondary ID [1] 313376 0
Nil
Universal Trial Number (UTN)
Trial acronym
NIKI-PT Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-operative intensive care 335769 0
Intensive Care Trauma 335770 0
Condition category
Condition code
Anaesthesiology 332593 332593 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single site study with the overall objective to evaluate the pharmacokinetics (PK) of nebulized ketamine in post-operative or trauma intensive care unit (ICU) patients. The study also aims to define the optimal dosing regimens to inform future clinical trails.

Design and setting:
A minimum 20 post-operative or trauma patients in the intensive care unit 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
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 received conventional 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 instruction 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 nebuliser 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 3mL of 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;
A monitoring plan has been established for the study, including a Safety Management Committee (SMC). Protocol adherence will be easily monitored as 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 the HREC approval, reportable adverse events as per protocol, clinical outcomes and protocol deviations.
Intervention code [1] 329977 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339910 0
To evaluate the plasma pharmacokinetics of single dose nebulized ketamine in post-operative and trauma patients in the ICU.
Timepoint [1] 339910 0
Plasma samples will be collected over a two hour sampling window where T=0 is the commencement of nebulization of the study drug. A total of 8 samples will be collected. T0, T+5, +10, +15, +30, +60, +90, +120 minutes
Primary outcome [2] 339911 0
Urine Creatinine Clearance
Timepoint [2] 339911 0
A two hour urine creatinine clearance will be collected on day of sampling where commencement of sample is the time of start of nebulization.
Primary outcome [3] 339912 0
Renal excretion of the study drug.
Timepoint [3] 339912 0
A 1 mL urine sample will be collected at the end of the sampling period from the total urine volume collected during the two hour creatinine clearance collection.
Secondary outcome [1] 441893 0
Safety
Timepoint [1] 441893 0
Monitoring for adverse events will occur during the study sampling period and up to 4 hours after end study drug nebulisation. Vital signs (heart rate, blood pressure, oxygen saturation) and GCS will be measured immediately prior to any study intervention (0min), also at 30min and 60min after cessation of nebulisation and up to 4 hours after the end of study drug nebulisation. Other adverse events reasonably suspected by the principal investigator to be related to study-specific nebulization procedures and blood collection will be continuously monitored from the start of study related interventions until 4 hours after the end of nebulisation. The SMC will meet after the 1st, 10th and final patient at end of study.
Secondary outcome [2] 443871 0
Feasibility of a large randomized controlled trial to provide effective analgesia as an adjunct for conventional therapy for pain management in the patient populations.
Timepoint [2] 443871 0
Pain monitoring 1. NPRS and RASS assessment at T=0 (baseline pre-dosing), 30 min, 60 min, end of study (2 hour post nebulization) 2. Break through analgesia during the two hour sampling period post-nebulization

Eligibility
Key inclusion criteria
Post-operative or trauma patient in the intensive care unit will be considered if they meet the following criteria:
* Adult greater than or equal to 18 years
* Has an arterial line or central venous line insitu
* Requiring analgesia as per treating team
* Able to provide consent to participate
* 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
* suspected or known hypersensitivity to ketamine
* already receiving intravenous ketamine for analgesia
* severe chronic lung disease
* systolic blood pressure less than 100 mmHg
* high oxygen requirement FiO2 greater than or equal to 0.4
* cardiac dysrhythmia
* receiving renal replacement therapy
* liver failure or Child-Pugh C liver cirrhosis
* pregnant or lactating patients
* history of significant mental health disorder or psychological distress as assessed by the PI that will impact consent and/or or prevent participation in the study
* delirium
* previous enrolment in the NIKI-PT 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 participants. 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
16/02/2025
Actual
Date of last participant enrolment
Anticipated
15/08/2026
Actual
Date of last data collection
Anticipated
16/08/2026
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 27342 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 43433 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 317819 0
University
Name [1] 317819 0
University of Queensland Research Fellowship
Country [1] 317819 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 320187 0
None
Name [1] 320187 0
Address [1] 320187 0
Country [1] 320187 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316503 0
Metro North Health Human Research Ethics Committee B
Ethics committee address [1] 316503 0
Ethics committee country [1] 316503 0
Australia
Date submitted for ethics approval [1] 316503 0
31/01/2024
Approval date [1] 316503 0
20/06/2024
Ethics approval number [1] 316503 0
HREC/2024/MNHB/105704

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

Contacts
Principal investigator
Name 138098 0
A/Prof Jayesh Dhanani
Address 138098 0
ICU Admin Level 3 Ned Hanlon Building Royal Brisbane & Women's Hospital, Butterfield Street, HERSTON QLD 4029
Country 138098 0
Australia
Phone 138098 0
+61 7 3646 8897
Fax 138098 0
Email 138098 0
jayesh.dhanani@health.qld.gov.au
Contact person for public queries
Name 138099 0
A/Prof Jayesh Dhanani
Address 138099 0
ICU Admin Level 3 Ned Hanlon Building Royal Brisbane & Women's Hospital, Butterfield Street, HERSTON QLD 4029
Country 138099 0
Australia
Phone 138099 0
+61 7 3646 8894
Fax 138099 0
Email 138099 0
jayesh.dhanani@health.qld.gov.au
Contact person for scientific queries
Name 138100 0
A/Prof Jayesh Dhanani
Address 138100 0
ICU Admin Level 3 Ned Hanlon Building Royal Brisbane & Women's Hospital, Butterfield Street, HERSTON QLD 4029
Country 138100 0
Australia
Phone 138100 0
+61 7 3646 8894
Fax 138100 0
Email 138100 0
jayesh.dhanani@health.qld.gov.au

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?

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.