Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12625001418460p
Ethics application status
Help: Ethics application status
Submitted, not yet approved
Date submitted
Help: Date submitted
28/11/2025
Date registered
Help: Date registered
17/12/2025
Date last updated
Help: Date last updated
17/12/2025
Date data sharing statement initially provided
Help: Data sharing statement date
17/12/2025
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
A first-in-human trial to assess safety of adenosine-lidocaine-magnesium (ALM) therapy for elective knee surgery
Scientific title
A first-in-human, single centre, open label exploratory study to evaluate the safety, basic pharmacokinetics and early clinical effects of intraoperative administration of ALM therapy to the knee of adult patients undergoing elective unilateral knee surgery
Additional trial identifiers [1] 316051 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
anterior cruciate ligament reconstruction 339919 0
Total knee arthroplasty 339920 0
Osteoarthritis 340060 0
Condition category
Condition code
Surgery 336145 336145 0 0
Other surgery
Musculoskeletal 336146 336146 0 0
Osteoarthritis
Musculoskeletal 336264 336264 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
ALM therapy is a combination therapy that comprises the following three individual actives in normal saline (0.9% NaCl): adenosine (1mM), lidocaine (3mM) and magnesium (2.5mM). The trial intervention involves intraoperative administration of a single dose (40 mL) of ALM therapy (adenosine, 10.69 mg; lidocaine, 32.5 mg; magnesium, 24.65 mg) into the knee of adult patients undergoing elective unilateral total knee arthroplasty (TKA) or anterior cruciate ligament (ACL) reconstruction surgery. ALM therapy will be administered by the attending orthopaedic surgeon as an intraarticular bolus at surgery end, immediately prior to skin closure. The concentration and total volume of ALM therapy to be administered is identical for trial participants in Cohort 1 (TKA) and Cohort 2 (ACLR).
Intervention code [1] 332666 0
Treatment: Drugs
Description of the comparator or control
No control group; each cohort will be assessed independently.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 343686 0
The primary outcome is safety, which will be assessed by the incidence of treatment emergent adverse events (TEAE). This includes but is not limited to bradycardia/tachycardia, arrythmias, hypotension, respiratory depression, neurological symptoms (i.e. headaches, dizziness, vomiting, blurred vision), hematologic abnormalities, coagulopathy and/or systemic biomarkers of organ injury.
Timepoint [1] 343686 0
Vital signs monitoring: * Commencement of anaesthesia to postoperative stage 1 recovery (~0 to 2h postoperative): continuous * Surgical ward to hospital discharge (~2 to 24h postoperative): 4-hourly Laboratory evaluations: Baseline and 24h postoperative. Patient-reported adverse events/adverse reactions: Recovery from surgery to 6-weeks postoperative.
Secondary outcome [1] 455302 0
Systemic inflammation.
Timepoint [1] 455302 0
Baseline, and 1h and 24h postoperative.
Secondary outcome [2] 455303 0
Systemic absorption of lidocaine following intra-articular (IA) administration of ALM therapy.
Timepoint [2] 455303 0
Baseline, and 1h and 24h postoperative.
Secondary outcome [3] 455304 0
Knee range of motion (ROM).
Timepoint [3] 455304 0
Baseline, and 6-weeks postoperative.
Secondary outcome [4] 455679 0
Patient-perceived knee function after TKA (Cohort 1).
Timepoint [4] 455679 0
Baseline, and 6-weeks postoperative.
Secondary outcome [5] 455680 0
Patient-perceived knee pain and function after TKA (Cohort 1).
Timepoint [5] 455680 0
Baseline, and 6-weeks postoperative.
Secondary outcome [6] 455681 0
Patient-perceived knee pain and function after ACL reconstruction (Cohort 2).
Timepoint [6] 455681 0
Baseline, and 6-weeks postoperative.
Secondary outcome [7] 455682 0
Patient-perceived health-related quality of life.
Timepoint [7] 455682 0
Baseline, and 6-weeks postoperative.

Eligibility
Key inclusion criteria
• Ability to provide written informed consent
• Adult (18 to 65 years); male or female indicated for elective unilateral primary TKA for OA (Cohort 1) or ACL reconstruction surgery for ACL rupture (Cohort 2)
• ASA I-II
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
• Participation in another clinical trial
• Any injection into the knee to be studied within the preceding 7 days
• Previous surgery on the index knee
• History of any cardiovascular (e.g. second- or third-degree AV block, sinus node disease, coronary artery disease, previous heart attacks, or peripheral artery disease), renal (e.g. acute/chronic kidney disease, renal inflammatory disease, polycystic kidney disease, renal stenosis), or neuromuscular disease (e.g. myasthenia gravis)
• History of bronchoconstrictive or bronchospastic lung disease (e.g. severe asthma, chronic obstructive pulmonary disease, emphysema)
• History of malignancy
• History of severe allergic or anaphylactic reactions
• Pregnancy
• Major bleeding disorder
• Clinically significant deviation from normal laboratory values
• Clinically significant abnormal ECG
• Systemic immunosuppressant agent within 6 months prior to treatment administration
• Known hypersensitivity to adenosine, lidocaine, or magnesium

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
Parallel
Other design features
Phase
Phase 0
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/03/2026
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 28835 0
Mater Hospital Pimlico - Pimlico
Recruitment postcode(s) [1] 45075 0
4810 - Pimlico

Funding & Sponsors
Funding source category [1] 320652 0
University
Name [1] 320652 0
James Cook University
Country [1] 320652 0
Australia
Primary sponsor type
University
Name
James Cook University
Address
Country
Australia
Secondary sponsor category [1] 323280 0
None
Name [1] 323280 0
Address [1] 323280 0
Country [1] 323280 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 319192 0
Mater Misericordiae Ltd Human Research Ethics Committee
Ethics committee address [1] 319192 0
Ethics committee country [1] 319192 0
Australia
Date submitted for ethics approval [1] 319192 0
28/10/2025
Approval date [1] 319192 0
Ethics approval number [1] 319192 0

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

Contacts
Principal investigator
Name 146554 0
A/Prof Peter McEwen
Address 146554 0
North Queensland Knee (NQK), 26 Graham Murray Place, Railway Estate, Townsville, Queensland 4810
Country 146554 0
Australia
Phone 146554 0
+61 7 47794788
Fax 146554 0
Email 146554 0
[email protected]
Contact person for public queries
Name 146555 0
Jodie Morris
Address 146555 0
Building 47 Room 113A, College of Medicine and Dentistry, 1 James Cook Drive, Bebegu Yumba campus, Townsville Queensland 4811
Country 146555 0
Australia
Phone 146555 0
+61 7 47814763
Fax 146555 0
Email 146555 0
[email protected]
Contact person for scientific queries
Name 146556 0
Geoffrey Dobson
Address 146556 0
Building 47 Room 113C, College of Medicine and Dentistry, 1 James Cook Drive, Bebegu Yumba campus, Townsville Queensland 4811
Country 146556 0
Australia
Phone 146556 0
+61 7 47814097
Fax 146556 0
Email 146556 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.