Efficacy and safety of Compound Chamomile-Lidocaine Gel for postoperative wound management after pediatric circumcision: a multicenter randomized controlled trial

Introduction

Circumcision is a commonly performed surgical procedure in pediatric urology, often indicated for phimosis, balanitis, or religious and cultural reasons. Despite its routine nature, postoperative complications such as pain, edema, delayed wound healing, and infection remain significant concerns for both clinicians and families (1). Postoperative wound care aims to minimize these complications by promoting a clean, moist healing environment, controlling inflammation, and reducing pain (2). After surgery, patients are instructed to use sterile gauze soaked in saline solution daily and to promptly clean any discharge around the suture area. If patients experience significant pain or discomfort, they are allowed to take 25–50 mg diclofenac sodium suppositories. A study in Sub-Saharan Africa suggests that those who received lidocaine-prilocaine cream before neonatal circumcision experienced significantly less pain (3). Thus, postoperative wound management in pediatric circumcision presents considerable clinical and research challenges, commonly accompanied by such adverse conditions as excessive bleeding, profuse exudate, and local edema.

Chamomile, derived from Matricaria chamomilla, has been traditionally used in herbal medicine for its anti-inflammatory, antimicrobial, and wound-healing properties (4). Studies have shown that chamomile extracts can inhibit pro-inflammatory cytokines and promote granulation tissue formation (5). Lidocaine hydrochloride, a widely used local anesthetic, provides rapid pain relief by blocking sodium channels in neuronal membranes (6). Systemic exposure after topical lidocaine depends on the total applied dose, surface area, duration of contact, and integrity of the skin/mucosal barrier; absorption can increase on damaged skin or mucosa, which is particularly relevant in the postoperative setting (7). However, published clinical and regulatory data for topical anesthetics generally indicate low plasma lidocaine concentrations with appropriate topical dosing, remaining well below levels typically associated with systemic toxicity, supporting primarily local action when application is restricted and non-occlusive (8). The combination of these two agents theoretically offers a dual benefit: reducing pain while accelerating wound healing through anti-inflammatory and antimicrobial effects. At the experimental dose, Compound Chamomile-Lidocaine Gel generally does not cause systemic toxic reactions due to excessive lidocaine hydrochloride absorption. Chamomile flower extract shows anti-allergic effects, and though local allergic reactions are extremely rare, the risk cannot be completely excluded in individual pediatric cases.

Studies on chamomile’s wound-healing properties are limited, but promising results have been reported in burn wound care (9) and diabetic ulcer healing (10). However, allergic/contact reactions, particularly in individuals sensitized to Asteraceae plants, have been described and warrant active surveillance (11). For lidocaine, its role in managing postoperative pain has been widely recognized, particularly in surgeries. However, evidence supporting their combined use in pediatric postoperative wound care, especially for circumcision, is scarce. We conducted a literature search and did not find any studies specifically using this compound gel in circumcision surgery. Thus, this multicenter study aims to fill this gap by evaluating the safety and efficacy of compound chamomile lidocaine gel in children undergoing circumcision, specifically those between 8 and 17 years old, providing a robust evidence base for its clinical application. We present this article in accordance with the CONSORT reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-aw-870/rc).

Methods

Study design and participants

This was a multicenter, randomized, parallel-group, controlled trial conducted across three tertiary pediatric hospitals in China from May 2024 to September 2024. The research protocol was approved by the Chinese Clinical Trial Registry (ChiCTR2400084075, https://www.chictr.org.cn/showproj.html?proj=228158) and the respective Ethics Committees of all participating institutions (Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, approval No. SCMCIRB-K2023095-2; Drug Clinical Trials of Wuhan Children’s Hospital, approval No. 2024D009-F01; Children’s Hospital of Nanjing Medical University, approval No. 202406027-1). Written informed consent was obtained from the parents or legal guardians of all participants. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Eligible participants were boys aged 8–17 years with a diagnosis of phimosis and an indication for elective circumcision. Both groups underwent the classical circumcision. The age range was selected to ensure reliable self-reporting of pain and compliance with the study protocol.

Inclusion criteria: males aged 8–17 years with phimosis, normal age-specific body mass index, planned classical circumcision, normal preoperative blood routine and coagulation (no surgical contraindications), and signed informed consent with follow-up commitment. Exclusion criteria: (I) preputial scars/stenosis (assessed by penile appearance, symptoms, discoloration and elasticity, or history of trauma/inflammation-related pain/itching); (II) congenital penile malformations, urogenital/genital infections (to avoid confounding postoperative wound outcomes and to ensure a standardized baseline), or history of balanitis/posthitis; (III) concurrent drugs interfering with efficacy evaluation, participation in other clinical trials, or history of allergies; (IV) inability to comply with treatment protocol, mental disorders, communication difficulties, or poor compliance.

Sample size

Through preliminary trial analysis of 40 cases previously, the proportion of patients with no edema in the test group after surgery was 42.1%, 42.1% was light, 15.8% was moderate, and 0% was severe. The proportion of edema-free in the control group was 10%, 55% was light, 15% was moderate, and 10% was severe. Using the Wilcoxon rank-sum test with a two-sided α of 0.05 and a power (1−β) of 80%, the required sample size was calculated to be 134 participants (67 per group). To account for an anticipated 20% dropout rate, a total of 180 patients were recruited (90 per group).

Randomization and blinding

Participants were randomized in a 1:1 ratio to the intervention (saline combined with Compound Chamomile-Lidocaine Gel) or control (saline alone) group using a computer-generated randomization sequence (SAS version 9.4). Randomization was performed using a block randomization method: 45 blocks (block size =4) were generated by a professional statistician, stratified across the three centers. Randomization codes were sealed in sequentially numbered opaque envelopes to ensure allocation concealment.

The outcome assessors were blinded to group assignments. The surgeons were aware of allocation due to the nature of the intervention, but all postoperative evaluations were performed by blinded independent reviewers.

Procedure

A total of 6 surgeons participated in the trial, including 5 attending surgeons and 1 resident (under direct supervision). All surgeons were credentialed in pediatric urology (or equivalent) and had ≥5 years of surgical experience. To minimize operator-related variability, all procedures followed a standardized operative protocol (classical circumcision) and perioperative management pathway, and surgeons received protocol training before enrollment. All surgeries were performed under general anesthesia using a standardized technique, which included the classical circumcision procedure with the same type of foreskin removal and the use of only absorbable suture materials throughout the process. After routine disinfection and draping, a circular incision was made 5 mm proximal to the coronal sulcus. Hemostasis was achieved with electrocautery, and the wound was closed with absorbable sutures.

Intervention group

The wound was washed with warm saline, and a 2–3 mm thick layer of Compound Chamomile-Lidocaine Gel (KAMISTAD^® GEL, STADA Consumer Health Deutschland GmbH, Bad Vilbel, Germany; containing chamomile tincture 200 mg/g and lidocaine hydrochloride 20 mg/g), was applied as a thin, uniform layer along the circumcision incision line, covering the glans and incision site (approximately a 1.5 cm ribbon of gel). Applications were performed tid for 14 days or until the incision heals. The wound was then dressed with Vaseline gauze and fixed with self-adhesive elastic bandages. The same dosing regimen was used for all participants because the intervention was topically applied to a localized surgical site, and the amount was standardized by coverage of the incision length rather than body weight.

Control group

The procedure was identical to that of the intervention group except that chamomile-lidocaine gel was not applied.

Both groups received complimentary rescue analgesic medication (potassium diclofenac suppositories, twice a day) as needed, with detailed documentation of analgesic consumption patterns maintained within 2 days. The Visual Analogue Scale (VAS) score is evaluated every 24 hours and is recorded by the guardian.

Postoperative care and follow-up

Both groups were discharged from the hospital on the second day after the surgery, and the initial dressing was removed on postoperative day 3. The evaluation of the results, particularly the assessment of the degree of edema, was conducted by five senior urologists who blindly evaluated three different-angle photos at the hospital. Subsequently, the wound was cleansed daily with saline. The intervention group then applied the compound gel three times daily for 14 days or until complete healing. The control group followed an identical cleansing regimen without gel application. All patients wore adjustable, loose-fitting post-circumcision protective underwear to minimize wound disturbance. The control group utilized saline irrigation without gel application, reflecting current clinical practice for circumcision wound management (12). The observation period extended to four weeks post-surgery. Upon enrollment and signing of the informed consent, each patient was provided with a medication record diary card. Additionally, a communication group was established for the parents of the enrolled children to facilitate follow-up management and reminders. A designated follow-up assistant was responsible for regularly checking in with the parents to ensure that proper post-surgical care and medication administration were being followed. All medications and care were administered by the parents on behalf of the children.

Outcomes

The degree of edema criteria: (I) none, soft skin at incision edges, no abnormal bulging; (II) mild, slight tissue bulging with visible skin folds; (III) moderate, moderate bulging with no visible skin folds; (IV) severe, severe bulging with loss of skin folds, shiny skin. And its scoring criteria are shown in Table 1. The representative images of the degree of edema are shown in Figure 1.

Figure 1 The representative images of the degree of edema. (A) None; (B) mild; (C) moderate; (D) severe.

Primary outcome

The severity of postoperative local edema at 1 week was assessed from standardized photographs by five independent and blinded senior physicians. The final grade for each patient was determined by the mode of the five scores.

Secondary outcome

Maximum VAS pain score within 48 hours (13), wound healing scores on days 3, 7, and 14 (14), time to complete wound healing (defined as a dry wound without discharge, scab detachment, and epithelial fusion) and infection rates at 7 and 14 days postoperatively, the cosmetic score of the incision at 4 weeks using a validated scar evaluation scale (15), and patient satisfaction with linear scarring using the patient scale (16).

Safety assessment and adverse event management

Given the pharmacokinetics (PK) profile of topical lidocaine (dose-/area- and barrier-dependent absorption) and the known potential for chamomile-related contact reactions, we need to pay attention to the following aspects.

• Anticipated AEs: local reactions (mild numbness, rare erythema/rash).
• Active safety monitoring: preoperative hypersensitivity screening, intraoperative/postoperative real-time observation, and graded assessment via CTCAE 5.0 during follow-up.
• Management plan: discontinuation of gel for suspected allergic reactions; symptomatic care (e.g., local cooling, topical emollients/anti-inflammatory treatment) for mild irritation; antihistamines for urticaria/pruritus as needed; prompt clinical evaluation for severe local reactions, infection, or systemic symptoms; and emergency management for anaphylaxis per institutional protocol.
• Withdrawal criteria: development of severe AE, clinically significant allergy, or any condition requiring prohibited concomitant medications.

Statistical analysis

Data analysis was performed on the full analysis set (FAS) and per-protocol set (PPS). Data analysis was performed using SAS 9.4 (SAS Institute, Cary, NC, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range, IQR) depending on normality and compared using independent-sample t-tests or Mann-Whitney U tests. Categorical variables were analyzed using χ² tests or Fisher’s exact tests as appropriate. The primary outcome (ordered edema grade) was analyzed using the Wilcoxon rank-sum test. A two-sided P value <0.05 was considered statistically significant.

Results

Patient demographics and baseline characteristics

A total of 186 eligible participants were enrolled, and 6 children were excluded. Among the 6 excluded children, 2 were unable to attend follow-up visits on time and 4 declined to be included in the study. Of the 180 participants randomly assigned to the two groups (90 per group). Five patients in the intervention group and seven in the control group were lost to follow-up, resulting in a PPS of 85 and 83 patients, respectively (Figure 2). Baseline demographic and clinical characteristics were comparable between the two groups (Table 2).

Figure 2 Clinical trial flow chart. FAS, full analysis set; PPS, per-protocol set.

Primary outcome

The blinded assessment of edema at 1 week revealed a statistically significant difference in the ordinal distribution of edema severity favoring the intervention group, in both the FAS (P=0.02) and PPS (P=0.02), as shown in Tables 3,4. When categorized, the incidence of moderate-to-severe edema was lower in the intervention group (PPS: 10.59% vs. 24.10%, P=0.04; FAS: 10% vs. 22.22%, P=0.06), as shown in Table 5 and Table S1.

Secondary outcomes

The results show that both in the FAS and PPS, the postoperative maximum VAS pain score on day 2 was significantly lower in the intervention group compared to the control group (FAS: 3.15±1.26 vs. 5.32±1.15, P<0.001; PPS: 3.12±1.28 vs. 5.29±1.17, P<0.001). Additionally, the wound healing time in the intervention group was significantly shorter than that in the control group (FAS: 11.13±3.99 vs. 12.56±2.62 days, P<0.001; PPS: 11.13±4.04 vs. 12.53±2.59 days, P<0.001). No significant differences were found between groups in wound healing scores at individual time points, 4-week cosmetic scores, patient satisfaction, or infection rates (as shown in Tables S2,S3).

Adverse events

Three adverse events (wound bleeding, unexplained fever, purulent discharge) were reported in the control group, all of which resolved with outpatient care. No treatment-emergent adverse events attributable to the study intervention were recorded during follow-up in the intervention group; no local hypersensitivity reactions (e.g., erythema/rash) or systemic symptoms (e.g., dizziness/nausea) were observed.

Discussion

Postoperative edema is a common and often distressing complication following pediatric circumcision. By significantly reducing edema, alleviating pain, and shortening wound healing time, Compound Chamomile-Lidocaine Gel offers a safe and promising alternative for postoperative care in pediatric patients.

Postoperative edema not only increases the discomfort experienced by patients but can also negatively impact wound healing by compromising tissue perfusion (17,18). In severe cases, excessive edema may lead to abnormal tissue proliferation, which can even necessitate further surgical intervention (17,19). Edema is fundamentally an inflammatory response to tissue injury, typically characterized by an accumulation of fluid in the interstitial space. This inflammatory process can delay healing by impairing oxygen and nutrient delivery to the wound site, as well as increasing the risk of infection and scarring (16). A growing body of literature supports the idea that reducing edema in the postoperative period can promote faster and more efficient wound healing.

Studies examining various pharmacologic agents and topical treatments have demonstrated their potential in mitigating edema after surgical procedures. Recent trials investigating corticosteroid application, cryotherapy, and even traditional herbal remedies have shown promising results in reducing postoperative swelling and facilitating tissue repair (20). The present study further adds to this body of evidence by demonstrating the efficacy of chamomile tincture in reducing postoperative edema. However, limited literature regarding studies on the efficacy of chamomile tincture in humans.

The intervention group in this study exhibited a notable reduction in moderate to severe edema at 1 week postoperatively, a finding with significant clinical relevance. Chamomile exerts anti-inflammatory and antioxidant effects that may contribute to reduced postoperative inflammation and edema. Its flavonoids (e.g., apigenin and luteolin) can inhibit the cyclooxygenase and lipoxygenase pathways, thereby decreasing the synthesis of key pro-inflammatory mediators such as prostaglandins and leukotrienes (21,22). In parallel, chamomile may help stabilize vascular permeability and downregulate inflammatory signaling, as extracts have been shown to reduce pro-inflammatory cytokines including IL-6 and TNF-α in experimental models (23). Beyond suppressing inflammation, chamomile has also been associated with enhanced collagen synthesis and improved wound remodeling—processes central to effective tissue repair and overall wound-healing outcomes (5,24).

With the increasing interest of postoperative wound management, there is an increasing focus on postoperative pain management. Ensuring a safe, pain-free recovery for patients is a key objective. Pain is one of the most distressing symptoms for children recovering from circumcision, often necessitating systemic analgesics. Lidocaine is a commonly used local anesthetic, and its efficacy in postoperative pain management is well established across various surgical procedures (25). In some analgesic regimens for circumcision, lidocaine is used alone or in combination with other drugs and methods (3). The significant reduction in VAS pain scores within the first 48 hours in the intervention group highlights the analgesic efficacy of lidocaine, complemented by the soothing properties of chamomile. Previous studies have shown that lidocaine reduces postoperative pain effectively in pediatric dental and minor surgical procedures (26). Also, a single-center study investigating the application of Compound Chamomile and Lidocaine Hydrochloride Gel in hypospadias repair patients demonstrated its significant efficacy in postoperative pain management (27). The findings revealed that this topical formulation provided substantial analgesic benefits, effectively alleviating postoperative discomfort in this patient population. Chamomile, known for its calming effects, likely synergized with lidocaine to further reduce discomfort (28). Because chamomile was not evaluated as a standalone component, its independent contribution cannot be confirmed in this study. Therefore, the combination of these two agents may enhance the overall analgesic effect.

The shorter wound healing time observed in the intervention group aligns with previous research on chamomile’s ability to promote re-epithelialization and granulation tissue formation (29). Similarly, lidocaine’s local analgesic effect may have indirectly facilitated wound healing by reducing pain-induced stress and improving patient compliance with wound care protocols. The potential mechanisms include improved blood circulation, reduced stress hormones, and increased compliance with prescribed care.

While the intervention significantly reduced edema, pain, and healing time, it did not improve wound healing scores on days 3, 7, or 14 or cosmetic outcomes at 4 weeks. This finding is consistent with studies suggesting that the primary role of chamomile and lidocaine is in the early stages of wound healing rather than long-term outcomes. Factors such as surgical technique, individual healing tendencies, and genetic predispositions likely play a more significant role in determining cosmetic outcomes (30).

The absence of adverse events in the intervention group is notable, emphasizing the safety of compound chamomile lidocaine gel in pediatric populations. Previous studies have reported rare allergic reactions to chamomile, particularly in individuals with ragweed allergies (31). However, no such events occurred in this study, likely due to careful screening and monitoring.

The study’s multicenter design enhances the generalizability of its findings by capturing diverse patient populations and clinical practices from different regions in China, and the study results indicate that the use of the gel led to a reduction in postoperative edema, which was accompanied by a decrease in pain and a shorter healing time. Nevertheless, future experiments should be conducted in other research populations/races to verify the results. These findings are significant for the recovery of children following circumcision. However, several study limitations warrant consideration. First, our follow-up period was restricted to four weeks, which may not capture long-term cosmetic outcomes or rare adverse events. Second, because this was a two-arm comparison (Compound Chamomile-Lidocaine Gel vs. saline) without a gel-vehicle control or component-specific arms, we cannot determine whether the observed benefits were driven by the active ingredients or the gel base. Third, our results may be most generalizable to boys undergoing elective circumcision without active preoperative penile inflammatory/infectious conditions (e.g., balanoposthitis), as such conditions were excluded to minimize outcome confounding. Future investigations with longer follow-up and an appropriate vehicle-control arm are warranted to confirm durability and clarify the mechanism.

Conclusions

This trial provides compelling evidence that Compound Chamomile-Lidocaine Gel reduces edema and pain while accelerating wound healing, addressing critical unmet needs in pediatric circumcision. The results of this study pave the way for broader clinical applications of Compound Chamomile-Lidocaine Gel, including its potential use in other pediatric and adult surgical settings. Future research should explore its long-term cosmetic outcomes, cost-effectiveness, and patient satisfaction to further substantiate its clinical utility.

Acknowledgments

Preliminary findings from this study were accepted as an e-poster presentation at the 45th International Congress of the Société Internationale d’Urologie (SIU), 2025.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-aw-870/rc

Trial Protocol: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-aw-870/tp

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-aw-870/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-aw-870/prf

Funding: This study was funded by the Pudong New Area Science and Technology Development Fund (grant No. PKJ2020-Y04), the Natural Science Foundation of Fujian Province (grant No. 2023J01183), and the Sanya Science and Technology Special Fund (grant No. 2022KJCX40).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-aw-870/coif). All authors report that this study was funded by the Pudong New Area Science and Technology Development Fund (grant No. PKJ2020-Y04), the Natural Science Foundation of Fujian Province (grant No. 2023J01183), and the Sanya Science and Technology Special Fund (grant No. 2022KJCX40). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Ethical approval was granted by the Ethics Committee of each hospital (Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, approval No. SCMCIRB-K2023095-2; Drug Clinical Trials of Wuhan Children’s Hospital, approval No. 2024D009-F01; Children’s Hospital of Nanjing Medical University, approval No. 202406027-1). Written informed consent was obtained from the parents or legal guardians of all participants. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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