The study is a randomized, double-blind, placebo-controlled trial design based on SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) reporting guidelines (Multimedia Appendix 1) [57], and the results will follow the CONSORT (Consolidated Standards of Reporting Trials) guidelines [58]. Our research project is scheduled to recruit patients from May 1, 2023, to April 30, 2025. All postoperative patients with Colles fracture will be recruited through referrals from orthopedic physicians at Changhua Christian Hospital. Researchers will screen and select participants based on specific inclusion and exclusion criteria. In this study, all participants are randomly assigned using a computerized block randomization schedule. We randomly generate a pool of 100 patients, who are assigned to sequentially numbered opaque envelopes. The treatment allocations are balanced within each group, with each group containing 50 patients. Researchers and patients are both blinded to the treatment allocation, with the exception of the statistician responsible for the randomization process. The two groups in the study consisted of the experimental group receiving RYJHS treatment and the control group receiving a placebo.

All participants undergo standard medical treatment after surgery and are involved in the efficacy assessment of RYJHS external application. Figure 1 shows the study’s flowchart. Both groups apply a patch plaster on the back of the wrist without wounds (avoiding the suture of the fracture operation). Figure 2 shows the site of the medication application. The experiment group apply the RYJHS plaster, while the control group apply a placebo plaster. The patch is applied twice a day, for 6 hours each time, with a 6-hour break in between, repeated for 3 days, completing one course of treatment. Patients undergo two courses of treatment, with the first course completed during hospitalization, and the second course completed 3 days after discharge.

To be eligible for our study, patients must meet the following criteria: be 20-80 years of age, have a Colles fracture (Frykman classification type I-VI) [59] diagnosis that has been treated with open reduction and internal fixation (ORIF) surgery, and provide informed consent either personally or through their family members.

The following exclusion criteria will be applied: age older than 80 years or younger than 20 years; inability to comply with experimental procedures or complete questionnaires; presence of wounds on the back of the wrist; allergy to the herbal patch before; use of other Chinese herbal topical medicine after fracture; pregnancy; cancer; stroke; and systemic diseases such as severe anemia, thyroid disease, and poorly controlled diabetes.

Our study closely resembles the design of phase-2 studies in clinical trials, which aim to assess the effectiveness of drugs in participants with specific conditions or diseases. We used G*Power (Heinrich-Heine-Universität Düsseldorf) to estimate the necessary sample size for our study, taking into account repeated-measures ANOVA within-between interactions with a medium effect size of f=0.25 and α level=.05. To achieve a statistical power of 0.95, we calculated a total sample size of 86 [60]. To account for potential dropouts and satisfy our inclusion criteria, we will enroll 100 individuals who have been admitted to our orthopedic care ward and diagnosed with Colles fracture after surgery.

RYJHS is a common TCM plaster that has been used for more than 500 years. RYJHS is composed of 10 herbs: Trichosanthis radix, Rhei radix et rhizoma, Phellodendri cortex, Curcumae longae rhizoma, Angelicae dahuricae radix, Magnolite cortex, Glycyrrhizae radix et rhizoma, Citri reticulatae pericarpium vetum, Atractylodis rhizoma, and Arisaematis rhizoma (given in Table 1). This herbal formula is a fixed prescription announced by the Department of Chinese Medicine and Pharmacy. The RYJHS used in our study is manufactured by Kaiser Pharmaceutical Co and meets the requirements of Good Manufacturing Practice. It has also been issued a drug certificate. The placebo powder, which uses computer color-matching technology in the color simulation of RYJHS [61], is also produced by Kaiser Pharmaceutical Co. Both RYJHS and the placebo are prepared by mixing 13 grams of powder with 23 mL of water, which is then evenly spread onto a cotton cloth and covered with gauze for later use. The aforementioned procedures are all carried out by the same experienced technician, as given in Figure 3.

In this study, we will gather data from each participant including their gender, age, affected hand and dominant hand, Patient-Rated Wrist Evaluation (PRWE) score, C-reactive protein (CRP) levels, wrist ultrasound results, wrist x-ray images, and Dyshidrotic Eczema Area and Severity Index (DASI) score. Patients who have undergone Colles fracture surgery are required to be evaluated, and data will be collected before the trial, as well as 3 days and 6 days after topical medication application. The participant timetable of enrollment, assessments, and treatments is given in Table 2. The primary outcome is the PRWE score, which is used to assess wrist function recovery. The PRWE score, collected via a questionnaire, was developed in Canada for patients with wrist problems to express their pain and level of function [62]. The secondary outcomes are CRP level and wrist imaging records, which are used to demonstrate the degree of inflammation and swelling reduction. In addition, the DASI score is used to monitor any allergic or adverse events that may occur at the application site [63].

We will conduct statistical analyses using the SPSS software (version 22; IBM Corporation). Descriptive analyses will be performed on demographic data using frequencies and percentages to characterize the sample. Categorical variables will be compared using chi-square tests, while continuous variables will be compared using 2-tailed t tests. We will use repeated-measures ANOVA to determine if changes in wrist function (the dependent variable) are due to the interaction between the “type of treatment” (RYJHS) and “time” (measurement time). Multiple regression will be used to assess the impact of latent factors on primary outcomes (wrist function) and secondary outcomes (swelling and inflammation), adjusting for all possible covariates. Regression models will be performed in different outcome groups to compare the effects of different treatments (RYJHS intervention vs placebo).

Approval for this trial (protocol ID 221006) was granted by the Institutional Review Board of Changhua Christian Hospital (CCH) on November 25, 2022, following the principles outlined in the Declaration of Helsinki. The study protocol has also been registered on ClinicalTrials.gov (NCT05638360). Individuals interested in participating will be required to provide written informed consent before the study’s initiation. They will receive comprehensive information about the study, including procedures, potential benefits, and risks, excluding specific details regarding the RYJHS medication. Participants are free to withdraw at any time without any impact on their future medical care.

Data collected will be anonymized to protect participants’ privacy, and all information will be kept confidential according to institutional data protection policies. No direct compensation will be provided to participants. The results of this research will be disseminated through publication in a peer-reviewed journal and presented at scientific conferences.

The primary clinical treatments for Colles fractures, such as closed reduction, casting, percutaneous fixation, external fixation, and ORIF, generally yield positive functional outcomes. However, both percutaneous and external fixation have reported a higher risk of infection, while percutaneous fixation has been shown to have a higher rate of soft tissue injuries [64,65]. Besides, the ORIF procedure including local dissection, reduction, and the insertion of plates or screws results in a higher incidence of tendonitis, tendon irritation, or tendon rupture [66,67]. In Taiwan, the routine conventional treatment for Colles fracture is ORIF surgery. However, operations often result in soft-tissue and lymphatic vessel damage. As a result, patients may experience heat, pain, redness, and swelling after the operation. The discomfort disrupts their willingness to undergo rehabilitation. Prolonged swelling can also affect the range of motion, hand function, muscle strength, and outward appearance of these patients [68]. Therefore, resolving pain and swelling is a significant problem for patients with Colles fracture after ORIF surgery.

The most common method of relieving swelling is ice packing. Ice packing can reduce swelling, capillary permeability, and delivery of inflammatory substances [69]. Besides, ice packing can decrease nerve conduction velocity, increase pain threshold, and provide analgesia [70]. However, many studies have reported that ice packing not only delays wound healing but also has a higher risk of cold injury [71,72]. Besides, pain management is also a concern for patients who undergo ORIF surgery. Physicians often prescribe opioids; NSAIDs; or a combination of opioids, NSAIDs, and steroids for pain management [73]. However, due to the potential side effects, these medications raise concerns for patients with diabetes, hypertension, gastrointestinal disorders, impaired liver function, or impaired kidney function.

There are several limitations in this study design. First, during the patients’ hospitalization, patients were assisted by nurses who ensured regular medication application. However, it may be challenging to confirm whether the patients continued to apply the medication on schedule after discharge. Therefore, it might be necessary to use phone reminders to engage caregivers in assisting with regular medication application. Second, theoretically, the closer the topical medication is applied to the lesion, the more effective it is likely to be. However, due to concerns about postsurgical wound infections, the application of topical medication needs to be avoided on the site of surgical incision. Therefore, for the purpose of this experiment, only the uninjured area on the back of the wrist can be selected for topical medication application. Finally, the inclusion criteria for the trial of Colles fracture did not encompass comminuted fractures; thus, the efficacy of RYJHS may not be evaluated in patients with severe Colles fractures.

This study represents the first randomized, double-blind, placebo-controlled trial to investigate the efficacy of RYJHS for postoperative Colles fractures. RYJHS, with its natural ingredients known for anti-inflammatory and antibacterial properties, could serve as a noninvasive adjunctive therapy to reduce postoperative complications and enhance functional recovery. Its application aligns with patients’ increasing interest in integrative medicine options that minimize reliance on pharmaceuticals. Future directions include exploring RYJHS’s active ingredients, assessing formulation efficiency, and developing a more accessible application method, which may strengthen RYJHS’s role as an adjunctive treatment for Colles fractures.

This randomized, double-blind, placebo-controlled trial aims to provide robust evidence of the efficacy and safety of RYJHS as a topical adjunctive treatment for postsurgical Colles fractures. With the potential to reduce inflammation and aid functional recovery, RYJHS could offer an alternative, nonpharmaceutical option for managing postoperative complications in patients with Colles fractures.