4.2. Study Design
MAY
This RCT was approved by the Hospital Ethics Committee and Scientific Board (Authorization n° 2556, 27 May 2020). The study protocol was registered on clinicaltrials.gov (NCT04426721). The study was performed in accordance with the Ethical Principles for Medical Research Involving Human Subjects outlined in the Declaration of Helsinki. All participants were fully informed about all experimental procedures and signed a written informed consent form prior to participation.A total of 52 patients were randomly divided into 2 different treatment groups: those receiving 3 weekly IA injections of O3 (Group A) versus those receiving 3 weekly administrations of high-molecular-weight HA (Group B).The randomization list (block randomization with block sizes of 8 patients) was provided by an independent statistician and kept in a dedicated office. Progressively numbered, sealed envelopes containing the treatment allocation (OT or HA) were used. The physician administering the treatment contacted the office just before performing the injection to know the patient allocation; the envelope was then opened to determine the treatment group and the patients included in the randomization list. Before the injection, the syringe was appropriately covered to prevent patients from discovering the substance they were receiving. The treatment consisted of 3 injections at 1-week intervals. Patients were then prospectively evaluated at baseline and at 1, 3, and 6 months after the injections. At the end of the study, the nature of the injected substance was revealed to the patients.