Effect of Topical Ozone on The Healing Diabetic Foot Ulcer

NCT ID: NCT05977309

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-01
• Study Completion Date: 2023-08-30

Brief Summary

Despite conflicting and contradictory evidence regarding its efficacy, some wound care centres have advocated and adopted ozone for treating DFU. However, there are gaps in the application of topical ozone therapy. Reported no significant impact on the healing process of DFU, and not all said that topical ozone can enhance the healing process. This study aimed to compare the efficacy of topical ozone therapy in conjunction with standard wound care versus routine wound care alone in treating DFU. The wound, ischemia, and foot infection (WIFI) scale was used to measure wound size, the tissue survival rate at DFU, infection, peripheral microcirculation, glycemic control, Hba1c control, and wound healing.

Detailed Description

Diabetic foot ulcer (DFU) is one of the most severe complications that diabetic patients can develop (1). The lifetime incidence of DFUs is estimated to range between 19% and 34%, and between 40% and 65% of diabetic patients experience recurrence within 1 to 5 years after ulcer healing (2). DFUs are prevalent: 6.3% globally and 5.5% in Asia (3). Patients with DFUs have an increased risk of recurrence, infection, necrosis, and ultimately amputation (2-4). The prevalence of diabetic ulcers in Indonesia is around 15%, the amputation rate is 30%, and the mortality rate 1 year after amputation is 14.8% (5). Diabetic foot ulcer patients have a high mortality rate of almost 50% within 5 years with one of the causes being infection (6). The most common reason for hospitalization of people with diabetes is DFU, where 25% are at risk (7) and 20% result in amputations (8). Moreover, according to a meta-analysis, DFU patients in the gangrenous stage have a high risk of amputation (9). DFU treatment costs the healthcare system and the patient's family a lot. DFU control requires specific attention (7). Topical ozone is a cyclic gas composed of three oxygen atoms (10), It can treat various diseases due to its different documented effects, such as its antioxidant and antibacterial properties. Ozone gas treats diseases and wounds, including DFU, in topical ozone therapy (11). Ozone is a gas consisting of three oxygen atoms that decompose swiftly. For instance, it can be used to treat chronic infections primarily caused by pathogens with antibiotic resistance (12).

Study design and participants, in five wound care clinics on Java Island, Indonesia, men and women with diabetic foot ulcer lesions participated in this randomised, triple-blind clinical trial. Inclusion criteria included women and men receiving treatment for diabetic foot ulcers, the WIFI scale, current blood sugar between 120 and 180 mg/dl, Hb1ac between 4.5 and 7%, lesion length greater than 5 cm, and infection. Exclusion criteria in this investigation, such as immunodeficiency disorders, are listed as examples. Sample size, G-Power software was used to calculate the sample size based on the diabetic foot ulcer wound healing variable in the study (11). Taking into account M1 = 39.1, M2 = 33.53, SD1 = 4.4, SD2 = 21.62, = 0.05, and Power = 95%, and taking into account the larger number of samples (n = 210) in each group and 15% attrition, the final sample size for each group was 215, for a total sample size of 430. Sampling, the researcher (first author) enrolled the study with the UHB office of research ethics and awaited a referral letter. Upon entering the room, he introduced himself to the DFU patient, assessed the wound using the WIFI scale, evaluated the inclusion criteria, and explained the purpose and methodologies of the study during wound care. Men and women who were eligible to participate and willing to do so submitted a written consent form. According to their medical records, researchers filled out demographic information. Participants were randomly assigned to ozone therapy and placebo groups in a ratio of 1:1 using block randomization with Random Allocation Software (RAS) and block sizes of 4 and 6. By the number of samples, envelopes were prepared, and capsules were deposited within them. 1 to 430 were assigned to each envelope. The envelopes were opened in the order that the participants entered the study, and the type of intervention was determined. A person uninvolved in the sampling process prepared envelopes in the allocation order. In this study, researchers, subjects, and outcome evaluators were all blinded. Intervention, during wound care, the topical ozone therapy group received a concentration of 30 mg/L at a frequency of 30 minutes per day for 30 days. Participants received ozone therapy topically every three days for eight treatments. The placebo group received standard wound care and education regarding DFU wound care. Both groups received instruction in DFU wound care, personal sanitation, and nutrition. According to the national protocol of the International Working Group on the Diabetic Foot, the same DFU wound care was administered to both groups (13). A document containing a table of the days of the week is provided to the individual, who is instructed to place a mark in the appropriate column each day following consumption. Patients were given a phone number to call if they had any queries or concerns. The degree of wound healing was measured using the Wound, Ischemic, and Edema Infection (WIFI) scale. The enumerator visited each participant at the wound care clinic (data collection and outcome evaluation). Data collection tool, demographic characteristics and the wound, ischemia, foot infection (WIFI) scale were utilised for participant inclusion (14), A summary of adverse events. Age, level of education, employment status, adequate household income, duration of diabetes, course of DFU treatment, number of sutures, blood sugar, Hb1AC, and ankle-brachial index were included as demographic variables (15), and toe ankle brachial (16), dll. Toe ankle brachial Wound, Infection, and Function (WIFI) are graded from 0 to 3. 0: no ulcer, 1: little ulcer, 2: deep ulcer with gangrene limited to toes, 3: extensive ulcer or infection or gangrene. Toe Pressure measures ischemic sites. 0: > 60 mmHg, 1: 40-59, 2: 30-39, 3: <30, while on infection, 0: No infection, 1: Mild (<22cm cellulitis), Moderate (>2cm/purulent), 3: Severe (Systemic response/Sepsis). Data analysis, the collected data were analysed with Jamovi software, and their normality was determined with the Kolmogorov-Smirnov test. Intention-to-treat (ITT) was utilised to analyse the outcomes. In this study, wound healing was regarded as the primary outcome, while infection and ischemia were secondary outcomes. Independent t-test and Multivariate Analysis of Variance (MANOVA) were used to compare the improvements in wound size, brachial toe index, transcutaneous oxygen, and infection between the two groups.

Conditions

Wound Heal; Diabetic Foot Ulcer; Ozone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Effect of Topical Ozone on The Healing Diabetic Foot Ulcer

The topical ozone therapy group received standard wound care with modern dressings every three days for thirty days.

Group Type: EXPERIMENTAL

Topical ozone therapy

Intervention Type: DEVICE

the topical ozone therapy group received a concentration of 30 mg/L at a frequency of 30 minutes per day for 30 days. Participants received ozone therapy topically every three days for eight treatments.

Effect of Standart Wound Care on The Healing Diabetic Foot Ulcer

The placebo group received standard wound care with modern dressings thrice weekly for thirty days.

Group Type: PLACEBO_COMPARATOR

Topical ozone therapy

Intervention Type: DEVICE

the topical ozone therapy group received a concentration of 30 mg/L at a frequency of 30 minutes per day for 30 days. Participants received ozone therapy topically every three days for eight treatments.

Interventions

Topical ozone therapy

the topical ozone therapy group received a concentration of 30 mg/L at a frequency of 30 minutes per day for 30 days. Participants received ozone therapy topically every three days for eight treatments.

Intervention Type: DEVICE

Other Intervention Names

ozone therapy

Eligibility Criteria

Inclusion Criteria

• Patients with diabetic foot ulcers, both male and female, include both sexes.
• Size wound 4-80cm
• Value toe brachial index between 4-7 mmHg
• Value transcutaneous oxygen (TcPO2) levels range 1-45 mmHg
• Infection, area of cellulitis 1-2cm

Exclusion standarts:

• Immunodeficiency conditions
• Concurent ilness
• Size wound >80cm
• Value toe brachial index (TBI) <4 mmHg
• Value crititcal for transcutaneous oxygen (TcPO2) is 0 mmHg
• Systemic infection and sepsis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Asmat Burhan

OTHER

Sponsor Role: lead

Responsible Party

Asmat Burhan

Chief Researcher in Nursing, Faculty of Health Sciences, Universitas Harapan Bangsa

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Asmat Burhan, MSN

Role: STUDY_CHAIR

Universitas of Harapan Bangsa

Locations

Griya Husada Clinic

Kediri, Indonesia, Indonesia

Countries

Indonesia

Related Links

https://doi.org/10.1016/j.dsx.2018.11.060

Diabetic foot ulcer is one of the common complications of diabetes disease that is costly and difficult to treat.

https://doi.org/10.1590/1677-5449.190070

New classification system for the threatened lower limb, based on the three main factors that have an impact on limb amputation risk: Wound (W), Ischemia (I) and foot Infection ("fI").

https://doi.org/10.1371/journal.pone.0239236

DFU patients in the gangrenous stage have a high risk of amputation.

http://doi.org/10.1007/s00203-020-01818-x

DFU treatment costs the healthcare system and the patient's family a lot.

https://doi.org/10.2147/TCRM.S255247

Clinical studies have provided evidence on the oxygen-ozone therapy effectiveness in low perfusion syndromes and hyperglycemia, as well as conditions with oxidative stress and inflammation. The oxygen-ozone therapy promotes faster recovery and enhances h

https://doi.org/10.1186/2045-9912-1-29

ozone administration can induce tolerance to oxidative stress and prevent free radical-mediated injury

https://doi.org/10.1016/j.amjms.2020.05.012

Diabetic foot ulcer patients have a high mortality rate of almost 50% within 5 years with one of the causes being infection

Other Identifiers

UHarapanBangsa

Identifier Type: -

Identifier Source: org_study_id