Local Hyperthermia Combined With Topical 3% Hydrogen Peroxide for Refractory Viral Warts

Randomized Single-blind Parallel Controlled Clinical Trial of Hyperthermia Combined With Topical 3% Hydrogen Peroxide for Refractory Viral Warts

1. Background of the Problem Viral warts result from infection of the skin or mucous membranes by human papillomavirus (HPV). Some patients develop refractory cases due to abnormal immune function, persistent viral presence, or recurrent warts. The clinical challenge in treating refractory viral warts lies in the limited effectiveness of single therapeutic approaches, high recurrence rates, and the fact that a significant proportion of patients are infected with high-risk or special HPV subtypes. These factors necessitate combined multi-modal treatments and genetic etiological screening.

2. Current Treatment Status Thermotherapy (44°C ± 2°C, 30 minutes per session): Studies have demonstrated that it can stimulate the activation of local immune cells (such as Langerhans cells), thereby enhancing antiviral immune responses.

   Hydrogen peroxide: It possesses antibacterial properties and promotes tissue repair. In keratinocytes, it can induce thermally induced pyroptosis, thereby enhancing the efficacy of antiviral treatment.

3. HPV genotyping Refractory viral warts are often associated with infection by specific high-risk or low-risk HPV subtypes (e.g., HPV 16, 18, 2, 4, etc.). HPV genotype is closely linked to treatment outcomes and recurrence rates.
4. Relevant pathogenic gene screening This involves exploring intrinsic patient susceptibility, such as genetic polymorphisms related to immune function (e.g., HLA typing or Toll-like receptor-related genes). It also includes screening for rare gene mutations, such as mutations in the GATA2, IL2RG, and DOCK8 genes, which lead to impaired viral clearance and a propensity to develop multiple viral warts.

Study Overview

• Status: Recruiting
• Conditions: Refactory Warts
• Intervention / Treatment: Device: An infrared hyperthermia device; Drug: Hydrogen Peroxide 3 % Topical Solution; Drug: Normal Saline (NS)

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xinghua Gao; Phone Number: 024-83282524; Email: gaobarry@hotmail.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Recruiting
      • Infrared hyperthermia device (Patent No: ZL 200820231952.4, Model: YY-WRY-V01, Liaoning Yanyang Medical Instrument Co., Ltd., China)
      • Contact: Phone Number: +86 13792269768
    • Shenyang, Liaoning, China
      • Recruiting
      • Infrared hyperthermia device (Patent No: ZL 200820231952.4, Model: YY-WRY-V01, Liaoning Yanyang Medical Instrument Co., Ltd., China)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- 1: Patients with a disease course of ≥2 years who have failed to respond to ≥2 treatment methods (such as topical ointments, cryotherapy, laser therapy, etc.)

2: The subject or their legal guardian is able to understand and sign the informed consent form/agree to participate in the study.

Exclusion Criteria:

• 1: The subject or their legal guardian is unable to understand and refuses to sign the informed consent form / refuses to participate in the study

  2: Individuals allergic to local hyperthermia or hydrogen peroxide;

  3: Subjects with tumors or other serious diseases are unable to complete this clinical study;

  4: Due to personal or other objective reasons, it is not possible to ensure timely treatment and follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trial group; Local hyperthermia combined with hydrogen peroxide	Device: An infrared hyperthermia device; (Patent No: ZL 200820231952.4, Model: YY-WRY-V01, Liaoning Yanyang Medical Instrument Co., Ltd., China) An infrared hyperthermia device was used to apply local hyperthermia at 44°C to the target warts(largest and most severe warts).The device includes a heating source, an infrared temperature monitor, an adjusting arm, a control circuit for temperature stabilization, and a display. It uses a tungsten-halogen lamp (wavelength: 760-2300 nm, peak at 1200 nm) to maintain the temperature of a 0.5*0.5 cm skin area within ±0.1°C using a non-contact infrared feedback system.Hyperthermia: Conduct 44-degree Celsius, 30-minute sessions. Do it daily for the first 3 days, then 2 sessions every 7 days for 24 weeks.; Drug: Hydrogen Peroxide 3 % Topical Solution; Dressing: Dress with a cotton ball soaked in 3% hydrogen peroxide one hour prior to each hyperthermia session. Local Hyperthermia treats the target warts(largest and most severe warts), while medication addresses all warts.
Placebo Comparator: Control group; Local hyperthermia combined with normal saline	Device: An infrared hyperthermia device; (Patent No: ZL 200820231952.4, Model: YY-WRY-V01, Liaoning Yanyang Medical Instrument Co., Ltd., China) An infrared hyperthermia device was used to apply local hyperthermia at 44°C to the target warts(largest and most severe warts).The device includes a heating source, an infrared temperature monitor, an adjusting arm, a control circuit for temperature stabilization, and a display. It uses a tungsten-halogen lamp (wavelength: 760-2300 nm, peak at 1200 nm) to maintain the temperature of a 0.5*0.5 cm skin area within ±0.1°C using a non-contact infrared feedback system.Hyperthermia: Conduct 44-degree Celsius, 30-minute sessions. Do it daily for the first 3 days, then 2 sessions every 7 days for 24 weeks.; Drug: Normal Saline (NS); The control group used normal saline as the placebo for wet compress, and the hyperthermia treatment was the same as that of the trial group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clearance rate of warts within 6 months	The complete clearance rate was defined as the proportion of patients with lesions that completely disappeared within 6 months of completing all treatments.	6 months after the first time of treatment.
Recurrence rate of warts	Recurrence was the proportion of patients with recurrence of lesions at the cured lesion site within 6 and 12 months after treatment.	recurrence was the proportion of patients with reappearance of lesions at previously cleared sites within 6,12 months after treatment.
Complete clearance rate of warts within 3 months	The complete clearance rate was defined as the proportion of patients with lesions that completely disappeared within 3 months of completing all treatments.	3 months after the first time of treatment.
HPV genotyping	Collect the tissue sample from the wart for HPV gene testing.	Pre-treatment and 3,6 months after the first time of treatment
Pathogenic Gene Screening Analysis	Collecting patient blood samples for pathogenic gene screening	Pre-treatment
Immune-related cytokines	Collecting the patient's blood samples to test immune-related cytokines	Pre-treatment and 3,6 months after the first time of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the size and number of warts at different points in time	Changes in the size and number of warts at different time points (1 week, 2 weeks, 3 weeks, 4 weeks, 12 weeks, 24 weeks)	At 1 week, 2 weeks, 3 weeks, 4 weeks, 12 weeks, 24 weeks follow-up
Occurrence of adverse events	occurrence of adverse events (short - and long-term adverse reactions) (e.g. blisters, erythema, nail changes, ulcers/scars, hyperpigmentation, hypopigmentation, erosion)	During treatment and follow-up
Patient satisfaction score	Self-reported satisfaction on a 5-point Likert scale (0=very dissatisfied, 5=very satisfied)	At 6-month follow-up
Curative effect of different types of warts	The cure of different types of warts (common warts, plantar warts, condyloma acuminatum) was followed up at 6 months.	followed up at 6 months.
Treatment-related pain intensity	Pain assessed by Visual Analog Scale (VAS) ranging from 0 (no pain) to 10 (worst imaginable pain)	During each treatment session (Day 1, 2, 3, 10, 11, 18, 19, 26, ....180)

Collaborators and Investigators

• Sponsor: First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Thermotherapy; Hydrogen peroxide; Refractory viral warts
• Additional Relevant MeSH Terms: Wounds and Injuries; Infections; Virus Diseases; DNA Virus Infections; Skin Diseases; Skin Diseases, Infectious; Tumor Virus Infections; Skin Diseases, Viral; Body Temperature Changes; Heat Stress Disorders; Papillomavirus Infections; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Hyperthermia; Warts; Organic Chemicals; Pharmaceutical Preparations; Inorganic Chemicals; Crystalloid Solutions; Isotonic Solutions; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Peroxides; Reactive Oxygen Species; Free Radicals; Hydrogen Peroxide; Saline Solution; Solutions
• Other Study ID Numbers: 2025-641-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No