Study Design This study is a randomized prospective controlled trial. All patients with complete ACL from the three orthopedic teams at UHWI will be screened for inclusion criteria ACL tears requiring reconstruction for the first time. Patients will be approached by the Research Assistant and once agreement to participate has been obtained, will be informed of the study and given an informed consent (Appendix A). All consents will be done by the Research Assistant not involved in patient care.
The recruitment will take place in a discrete room within Orthopedics outpatient department where the patient will be informed of the details of the study and the right to participate or refuse. It will be reinforced that refusal to participate will not void the standard of care offered to patient. The study will be conducted over a two (2) year period in the Main Operating Theatre. The information gathered will be stored on a password encrypted computer stored in the Principal Investigator's office which can be accessed only by the Investigator or Principal Investigator. Data will be analyzed using Statistical Package for the Social Sciences (SPSS)
Meta analysis and subsequent prospective randomized studies have estimated that tourniquet use would be expected to be associated with poor visibility in only 0-3% of arthroscopic knee procedures. Excellent visibility would be expected in 90% to 97% of cases while no tourniquet would produce good or excellent visibility in approximately 80% of procedures (36, 37). A construct of 2 pairs of simulation populations with a) 97% scores of 1 (excellent visibility) in both the control and experimental groups and b) 97% scores of 1 in the control group and 80% scores of 1 in the experimental group. When the two populations with no stochastic difference were sampled, a sample size of 30 per arm was adequate to produce a BF\_10 greater than 3 (i.e. support for the alternate hypothesis) for 90% of samples. Conversely, for two populations where there is a stochastic superiority of the control to the experimental, a sample size of 20 per arm produces a BF\_10 less than 1/3 (i.e. support for the null hypothesis) for 90% of samples. We will be analyzing on an incremental basis and stop patient accrual when we either achieve a BF\_10 greater than 10 or less than 1/10 (strong evidence for the alternate or null hypothesis) (35) or we achieve a cumulative sample size of 60 patients.
Research Procedures/Protocols - Data Collection/Research Intervention Procedures
Patients will be randomized with the help of an online randomization tool Randomization tool @ https://ctrandomization.cancer.gov/tool/ (National Cancer Institute Clinical trial randomization tool) being placed in one of two arms: TXA alone and Torniquet alone.
Patient Recruitment A flyer (Appendix A) will be placed at strategic areas (e.g. cashiers, radiology department, physiotherapy department) advertising the study. Patients will be seen in the Outpatient orthopedic clinic and once the diagnosis of a Complete ACL tear is made, the patients will be recruited by the Research Assistant who is aware of the protocols and nature of study. The recruitment will continue until the quota is met; with a further follow up of up to 12 weeks post-surgical intervention.
Patients meeting the inclusion criteria will be informed of the study and once agreement to participate is obtained, will be invited to a private room to go through the consenting process. All consents will be done by the Research Assistant at that clinical visit. The time taken to perform the surgery after consent will be based on surgical time availability and patient finances, both of which should not distort standard of care or patient outcomes. All data obtained will be digitized and stored on a secure encrypted hard drive stored in the office of the Principal Investigator only accessible by the research team.
Procedure Administration The procedure will take place in the Main Operating Theatre. Patients will be randomized by the online randomization tool and assigned a study ID number, and a study group. This will be logged by the Research Assistant and information kept stored in the principal investigator's office computer. The participant will be transported to the operating theatre with a sealed envelope affixed to their docket containing that study ID number issued.
The Research Assistant will collect the envelop and reference the number with a randomization chart provided syncing the groups assigned.
The Research Assistant in a separate designated room will aspirate either TXA (10 mL, 1g) or saline (10 mL) alone dependent on the number given by the randomization tool. The aspirate will be placed in a marked syringe and given to the patient via intravenous transfusion of 100 mLs saline over a 10-minute period.
All patients to undergo Arthroscopic ACL reconstruction after being assigned to their respective groups and randomized intervention, will receive TXA (10 mL, 1g) in 100 mLs of saline. The control group will receive 110 mLs of saline total 10mins prior to surgery at the same rate and the same route. This will be administered by the anesthetic team under the guidance of the independent team Research Assistant. The surgeon and patient will be blinded, however the anesthesiologist will not be blinded.
Surgical Technique All patients will be positioned supine and administered spinal anesthesia. In all cases the application of a pneumatic torniquet will be applied to the proximal thigh after induction of anesthesia but will not be inflated for the group receiving TXA. Dependent on the randomized groups assigned; The standard torniquet pressure of 300 mm Hg will only be inflated for persons assigned to the torniquet group who will receive normal saline intravenously. Only the Research Assistant and the anesthetic staff will be aware of whether inflation of torniquet was applied. No other methods of hemostasis will be used for example, e.g., intra-articular cautery, Saline diluted epinephrine aliquots or 4 °C normal saline irrigation.
Postoperative Care Post ACL harvesting, the patients will undergo the standard two portal knee arthroscopy with a pressure pump injector set at the standard 30 psi. Visibility will be assessed using a 3 pronged questionnaire about intraoperative visibility by the main surgeon (7) which was shown to be better validated and with less inter-observer bias than 10-point scoring systems, with 3 being complete lack of vision and 1 being complete clarity (Appendix E).
The proposed start time of the study is July 2024.
Assessment of Risks and Benefits This research is a moderate risk study. The potential risks of tranexamic and physiological risk of thromboembolic phenomenon although proven highly unlikely must be considered (38).
Pneumatic torniquet being used as a standard of care in ACL reconstruction does have its negative such as compartment syndrome, neurapraxia due to prolonged compression, quadriceps lag and prolonging rehabilitation (39). The study has strict guidelines to ensure safety, hence the recommended 300 mm Hg pressure for inflation.
The benefit of this study is to gain the awareness of tranexamic acids use its vast potential as an alternate alternative standard of care in improving visibility during arthroscopic ACL reconstructive surgery.
No patient will be coerced to participate. No intervention deemed clinically necessary would be withheld from any participant or any who refuse consent.
Confidentiality Each patient will be assigned a study number which will be logged and kept by the research team. Information will be stored on a storage device that will be password protected stored in the principal investigator's office and accessed only by the research team.
Compensation and payments There will be no waiver of clinic fees as outpatient department clinic reviews at 2 weeks and 3 months are the normal standard of care for all patients. No compensation will be given to patients who consent to participate in the study.
Funding Funding if needed for this project will be provided by the research team. (Appendix C)
Expected Outcome Findings of the study will be used for publications and/or presentations both locally and internationally.
Ethical Considerations Ethical guidelines will be adhered to following the approval of the Mona Campus Research Ethics Committee (MCREC). Patients will be given a chance to ask questions and consider their participation freely during the informed consent process. Patients will be advised of their right to withdraw from the study at any point without the need for an explanation and care will not be withheld from those who do not participate. Patients' autonomy and dignity will be always protected.
Conflict of Interest There is no conflict of interest with the manufacturers of the drug being studied
Fair Selection of Subjects Subjects will be selected only because of the specific problem under investigation (i.e. patients with the condition Complete ACL rupture), being seen in the Orthopedic Outpatient Department at the UHWI or privately.) No participant in this study will be chosen due to easy availability, diminished autonomy, or social bias.
Limitations:
The foreseeable limitation to the study is the surgeon not being blinded can be prevented by:
1. Allowing main surgeons in the Operating theatre after all interventions and controls have been performed.
2. Post preparation of the surgical field with sterile drapes. However, if these measures fail to prevent blinding mitigating measures include
1\. Patient data would have to discarded. 2. A second surgeon as experienced absent during intervention or control would assess visual clarity as well based on the scale provided.
Impact of the study:
The results will be disseminated at academic meetings, international presentations and published in a peer review journal.
