This was a multicenter, randomized, positive-controlled study involving patients with HZ, using the He–Ne laser as the positive control. Five study centers in China participated in the study from August 2022 to April 2024: the Second Affiliated Hospital of Anhui Medical University, Hefei; China-Japan Friendship Hospital, Beijing; First Affiliated Hospital of Wenzhou Medical University, Wenzhou; Hangzhou Traditional Chinese Medicine Hospital, Hangzhou; and Shijiazhuang Traditional Chinese Medicine Hospital, Hebei.

The trial was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committees of the Second Affiliated Hospital of Anhui Medical University (SL-QX2021-005; 2021.09.03), China-Japan Friendship Hospital (QX2022-032-01; 2022.11.28), First Affiliated Hospital of Wenzhou Medical University (SL2022-133; 2023.01.16), Hangzhou Traditional Chinese Medicine Hospital (2023LL024; 2023.09.15); and Shijiazhuang Traditional Chinese Medicine Hospital (23/09/01-01; 2023.09.28). Its design, implementation, and reporting adhered to the Good Clinical Practice guidelines for medical device clinical trials, Helsinki Declaration (2013), relevant regulations from the National Medical Products Administration, and ethical committee recommendations. The study protocol, electronic case report form, informed consent form, and other written materials provided to the participants were approved by the ethics committees at each participating hospital. Before initiating any study-specific procedures, all patients were required to sign informed consent forms.

The sponsor (Hefei CAS Ion Medical and Technical Devices Co., Ltd., Hefei, China) and principal investigators were responsible for the design and conduct of the study. This study has been registered at www.chictr.org.cn (ChiCTR2300069993).

We enrolled patients who met the following criteria: aged between 18 and 75 years; diagnosed with HZ; rash onset within 7 days and with distinct blisters. Key exclusion criteria included severe or atypical HZ, concomitant pustular or wound infections, severe systemic diseases, human immunodeficiency virus (HIV)-infected individuals, patients with immune deficiencies, those using other medical electrical devices, individuals allergic to He–Ne lasers, acyclovir, or other substances, pregnant or lactating women, and patients who had used antiviral treatments, oral corticosteroids, or analgesics in the week before randomization.

The CAP device used in the experimental group, the ST-P101 plasma skin therapy instrument, was designed and produced by the Hefei CAS Ion Medical and Technology Devices. This device activates air through a built-in high-pressure excitation source, ionizes the gases in the air (e.g., oxygen and nitrogen), and uses a specially designed treatment head (comprising a 1-mm-diameter copper needle) to generate low-temperature plasma via high-voltage electrodes. The plasma in this state sterilizes and repairs damaged areas, providing a therapeutic effect on the affected site. The plasma skin therapy instrument is equipped with a control system that regulates the plasma output energy, ensuring controlled plasma effects.

The low-voltage electrode was attached to the skin, and the plasma parameters of the CAP device were as follows: the standard load was 140 MΩ and standard output power was 1.4 W. The device head was kept 10 mm from the skin lesion. The equipment and operation diagram are shown in Fig. 1.

The clinical trial instrument and treatment photos. a ST-P101 plasma skin therapy instrument. b High-voltage discharge tip. c Patients with HZ receiving CAP treatment

The control group used a medical device, the PL-300A He–Ne laser therapy device (Jiangsu Furei Technology Co., Ltd., Nanjing, China). The parameters were as follows: wavelength 632.8 nm, power supply AC 220 V/50 Hz, with a maximum visible laser output of ≤ 36 mW.

Patients were randomly categorized into the CAP and He–Ne laser groups. All patients received basic treatment with oral acyclovir 400–800 mg per dose, five times a day, for 7–10 days. Analgesic medications (such as pregabalin or gabapentin) and neurotrophic drugs (such as mecobalamin and vitamin B1) could be used at the investigator’s discretion based on the patient’s pain condition.

For device-assisted therapy, a visibly blistered skin lesion suitable for instrument treatment and evaluation was selected. The lesion area and pain condition were assessed. Device-assisted treatment and drug treatment started on the same day. Before the first treatment, blister fluid was aspirated from both groups and the selected lesion area was treated. The CAP group received CAP treatment once per day for at least 2 min per treatment area. The He–Ne laser group received treatment with a He–Ne laser therapy device once daily for 20 min per session. Photographs of the selected area were captured pre and post treatment. The device-assisted treatment was stopped once the wound had completely scabbed. If the wound had not fully scabbed after 10 days of treatment, no further treatment was performed. Follow-up visits were conducted at 3 ± 1 and 10 ± 2 days after treatment completion.

The primary endpoint was the efficacy rate, defined as the percentage of patients in each group whose treated area showed drying of blisters in ≥ 50% of the area after the final treatment. The secondary evaluation indicators included treatment duration (in days), the onset time of scabbing, scab rate, pain scores, and quality of life scores. Pre and post treatment and at follow-up, the treatment area was photographed and archived, and the images were evaluated by dermatologists who were unaware of the treatment being applied.

The treatment duration refers to the actual number of days the participants used the device, up to a maximum of 10 days. The onset time of scabbing was defined as the time when the first scab appeared after the initial treatment, and its rate was defined as the percentage of participants in each group who developed scabbing at the lesion site. Pain scores were assessed using the visual analog scale (VAS), where the participants marked the position on the scale that best represented their pain level. The investigator then measured and recorded the corresponding VAS score using a ruler of the same length, with results rounded to one decimal place. Quality of life scores were assessed using the EuroQol 5-Dimension 5-Level Health Questionnaire (EQ-5D-5L), including a brief descriptive system and VAS (EQ VAS). The health status generated by the descriptive system can be converted into a summary utility index using a “utility value set,” which ranges from 0 to 1, with a value closer to 1 indicating a better health state.

The safety evaluation indicators included the incidence of clinical adverse reactions, treatment-emergent adverse events (TEAEs), adverse events (AEs), and laboratory tests. Adverse reactions and the occurrence of normal and serious AEs were collected and recorded during the clinical trial and categorized by intensity, seriousness, and causality. Laboratory tests, including routine blood, liver and kidney function, and blood glucose analyses, were performed on patients before the first treatment and within 3 days after the final treatment.

The operator simultaneously recorded any equipment defects for both devices during treatment. Performance indicators were assessed using the Likert scale, with scores and evaluations based on three aspects: stability of the control panel, smoothness of operation by the researcher, and flexibility of the operating handle.

Programming and data analysis were performed using the Statistical Analysis System (version 9.4, SAS Institute Inc., Cary, NC, USA), and statistical significance was set at p < 0.05.

For continuous variables, statistical data are presented as number of observations (N), arithmetic mean (mean), standard deviation (SD), median value (median), 25th percentile (Q1), 75th percentile (Q3), minimum value (min), and maximum value (max). Categorical variables are described as frequencies, proportions, incidence rates, and composition ratios.

For intergroup comparisons of quantitative data, either a two-sample t test (for data with homogeneous variance and normal distribution) or Wilcoxon rank-sum test was used. Categorical data were compared using the chi-square test or Fisher’s exact test (when the chi-square test was not applicable), depending on data distribution. Intergroup comparisons of efficacy rates were conducted using the Cochran–Mantel–Haenszel chi-square test, accounting for central factors to correct their influence. A group t test or Wilcoxon rank sum test was used to compare differences in treatment duration, the time of scabbing, pain score, EQ-5D-5L effective index, and EQ VAS between groups.

Ordinal data were analyzed using the Wilcoxon rank-sum or Cochran–Mantel–Haenszel tests. For proportions ≤ 10% or ≥ 90%, the Clopper–Pearson method was used to calculate the 95% CI. For proportions between 10% and 90%, the Wald method was applied to calculate the 95% CI.