None listed
Conditions
Brief summary
Adenosine, lidocaine, and magnesium (ALM) therapy is a combination drug that has been shown to minimise surgery-induced inflammatory responses, improve tissue healing and reduce postoperative complications in experimental models of orthopaedic surgery. Although each of the ALM components are currently approved and used individually in the clinical setting, their combined use in humans has not yet been evaluated. Therefore, the purpose of this study is to conduct a first-in-human trial to evaluate the safety of a single dose of ALM therapy administered to the knee of adult patients whilst they are undergoing elective total knee arthroplasty (TKA) (Cohort 1) or anterior cruciate ligament (ACL) reconstruction surgery (Cohort 2). A total of 12 participants will be enrolled, with 6 participants in each surgical cohort. The primary objective is to evaluate safety, while secondary (exploratory) objectives include assessment of basic pharmacokinetics and early clinical effects to 6 weeks postoperative. This information is critical in determining ALM’s safety profile and to inform the design of a future clinical trial to determine the therapeutic dose range, and to assess efficacy of ALM therapy for orthopaedic applications.
Interventions
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 t
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).
Sponsors
James Cook University
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
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
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
Outcome results
None listed