Explanation for the choice of comparators

Steroid injection is a mainstream treatment for managing pain after the UGPL.

Injection of steroids may reduce inflammation, relieve pain and accelerate functional recovery. Therefore, we decided to use a compound betamethasone as a comparator.

Intervention description

All patients will be irrigated with single-needle technique [22]. Specifically, patients lying supine have a sterile sheet applied after skin antisepsis over the area of interest. Under the guidance of continuous ultrasound, using an in-plane approach, a No. 16 needle will be inserted into the calcification center along the long axis of the tendon after local anesthesia. The needle is connected to a 10 ml syringe with 5 ml of room-temperature normal saline. After gently injecting normal saline into the calcification, the calcific material will reflux back into the syringe with the saline when the piston is released. Repeat this step several times until the backflow saline changes from turbidity to clarity, and pay attention not to damage the calcific margin. The calcification can be slightly fragmented with a syringe needle in the event of difficulty to aspirate at the beginning. Finally, 5 ml of ozone with a concentration of 30 µg/milliliter will be injected into the SAB in the ozone injection (Ol) group [23], while the corticosteroid injection (CI) group received 5 ml mixture solution (the drug composition is compound betamethasone 0.25 ml + vitamin B12 0.5 ml + 2% lidocaine 1 ml + normal saline 3.25 ml) [24]. Finally, an ice pack will be applied to the puncture point for 20 min. All patients will be systematically treated with 0.2 g celecoxib orally for 48 h, avoid strenuous activities, and return for another visit one week later. All interventional procedures will be performed by the same experienced therapist.

Criteria for discontinuing or modifying allocated interventions

Participants can withdraw from the study at any time for any reason without consequences. The participant data that have been collected up to that moment will be included in the analysis. Serious adverse events such as infection and tendon laceration at any stage of treatment will be considered for early termination of the study.

Strategies to improve adherence to interventions

In this study, specific nurses will be arranged to contact patients regularly to monitor their progress and collect data. If the patient does not return as scheduled, the nurse will contact them by telephone.

Relevant concomitant care permitted or prohibited during the trial

New physiotherapy measures are prohibited during the trial, such as acupuncture and extracorporeal shock wave therapy. A rehabilitation program is permitted during the study.

Provisions for post-trial care

There is no compensation insurance in this study because no serious complications were found in our previous study [24]. The interventions used in this study were considered safe. It is expected that the patient will not suffer personal injury from participating in the trial. If the implementation of the study results in a health hazard to the patient, they will be treated in the appropriate hospital. The cost of treatment will be borne by the patient’s medical insurance.

Outcomes Primary outcome

The primary outcome is the numeric rating scale for pain (NRS)at 1 week (primary time point) and 3 months (secondary time point) following the procedure [25]. NRS is a commonly used clinical pain assessment tool, which is simple and reliable.

Specifically, take a standard horizontal ruler with a length of 100 mm, and the scale indicates different degrees of pain. On the leftmost side of the level ruler (0 represents “no pain”), the rightmost side (100 represents “the worst pain imaginable”), patients draw marks on the horizontal line according to their painful feelings. The minimum clinically important difference(MCID) in NRS score has been calculated to be 1.6 cm for patients with RCCT [26].

Secondary outcomes

The secondary outcomes include a multi-dimensional evaluation of shoulder disability and quality of life improvement measured on the Western Ontario Rotator Cuff index (WORC) [27], the University of California at Los Angeles shoulder scale(UCLASS) [28], the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) [29], the Rotator Cuff Quality-of-life Messure(RC-QOL) [30], the degree of calcification absorption, and the number of multiple treatments and incidence of adverse events.

The WORC is specifically designed to assess shoulder function and quality of life in patients with rotator cuff disorders, consisting of 21 questions divided into five parameters: physical symptoms, sports and recreation, work, social function, and emotional disorders. Each item is in the range of 0 mm (best) to 100 mm (worst). Total score 0 ~ 2100, higher scores indicating worse status.

The UCLASS is a comprehensive evaluation scale with five domains, including pain, function, active forward flexion, forward flexion intensity, and patient satisfaction. Pain and function are scored independently and both range from 1 (worst score) to 10 (best score). The remaining three parameters are given a maximum score of 5 points. Total score range from 2 ~ 35 points. The higher the score, the better the function.

The Dash is a questionnaire to evaluate the impairment degree of affected limbs functional, which contains 30 indicators. Each index has 5 grades from 1 “no difficulty, no symptom, or no impact” to 5 “unable to complete, very severe symptom, or high impact.” The total score is the sum of these 30 indexes, and then convert it to 0–100 points with the following formula:[(sum of score/n) − 1] × 25, where n is the number of completed responses. A higher score reflects severer disability.

The RC-QOL is a specialized scale to assess the quality of life in patients with rotator cuff disease. The questionnaire includes 34 items covering five areas: symptoms and physical complaints, sports and recreation, work-related concerns, lifestyle issues, and social and emotional issues. Score 0 ~ 100 for each item, summarize the answers of 34 items to form a total score, and then convert to 0 ~ 100 points. A higher score indicates a higher quality of life.

The degree of calcification absorption: using a semi-quantitative evaluation by X-ray as below: no change or minimal changes; the size of calcification decreases by less than 50%; calcification decreases between 50 and 90%; and the size of calcification decreases or disappears by more than 90% [7].

The number of multiple treatments: patients receiving two or more treatments will be recorded. The indication of repeated UGPL procedure is persistent clinical symptoms with calcification deposition, and there is no other cause leading to shoulder discomfort(such as shoulder periarthritis or subacromial bursitis) [31]. A minimum period of each UGPL procedure shall be 4 weeks apart.

The occurrence of adverse events, including abnormal bleeding, infection, and tendon tear, will be recorded throughout the study.

Participant timeline

All patients will have five evaluation appointments as follows: pretreatment, at 1 week, 1 month, 3 months, 6 months, and 12 months post-treatment.The detailed schedule for assessments is provided in Table 1, and the flow chart of this study is presented in Fig. 1.

Table 1 Schedule of enrolment, interventions, and outcome assessment Fig. 1

Flowchart of the trial. NRS, numeric rating scale; WORC, Western Ontario Rotator Cuff index; UCLASS, the University of California at Los Angeles shoulder scale; DASH, the Disabilities of the Arm, Shoulder and Hand questionnaire; RC-QOL, Rotator Cuff Quality-of-life Messure

Sample size

We use PASS statistical software to estimate the sample size. The sample size is estimated based on the NRS as the primary outcome measure. The MCID for NRS was defined as 1.6 cm. Earlier research has found that the SD of the NRS is 2.56 points [31]. The one-sided alpha level and statistical power are set to be 2.5% and 80% respectively, each group requires 42 patients. To allow for a 20% rate of loss to follow-up, at least 100 patients will be required to enroll in total.

Recruitment

The recruitment period runs from 8 September 2022 to 8 April 2023. Patients will be recruited at the pain clinic of Sichuan Provincial Orthopaedic Hospital.