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Effect of Topical Ozone on The Healing Diabetic Foot Ulcer

Primary Purpose

Wound Heal, Diabetic Foot Ulcer, Ozone

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Topical ozone therapy
Sponsored by
Asmat Burhan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wound Heal focused on measuring ozone, wound healing, diabetic foot ulcer

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion standarts: 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Effect of Topical Ozone on The Healing Diabetic Foot Ulcer

    Effect of Standart Wound Care on The Healing Diabetic Foot Ulcer

    Arm Description

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

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

    Outcomes

    Primary Outcome Measures

    Comparison of the effects of topical ozone therapy and placebo on the healing of diabetic foot ulcers.
    Comparing the healing of diabetic foot ulcers in the topical ozone therapy group with the control group. The dimensions of a wound can be assessed for wound-healing purposes by employing a photographic apparatus to quantify the length and width of the wound.

    Secondary Outcome Measures

    Comparison of ischemia to variations in skin oxygen levels by transcutaneous oxygenation (TcPO2) assessment of topical ozone therapy and placebo in diabetic foot ulcers
    Differences in epidermal oxygenation levels between diabetic foot ulcers treated with topical ozone therapy and those treated with ozone. The utilization of a scale questionnaire (WIFI) for measurement. The measurement of oxygen levels in the skin to assess ischemia can be conducted using transcutaneous oxygen (TcPO2) measurements, employing the PeriFlux 6000 instrument, which provides a measurement scale. In the context of blood pressure, the categorizations are as follows: normal blood pressure is defined as being greater than 45 mmHG, mild blood pressure falls within the range of 40-45 mmHg, moderate blood pressure ranges from 20-39 mmHg, severe blood pressure is within the range of 1-20 mmHg, and critical blood pressure is defined as being at 0 mmHg.
    Comparison of improvement in peripheral microcirculation from ischemia in diabetic foot ulcers between topical ozone therapy and a control group using the toe ankle-brachial index (TBI) measurement.
    Comparing the improvement in peripheral microcirculation of the foot in diabetic foot ulcers treated with topical ozone versus those treated with ozone. The utilization of a scale questionnaire (WIFI) for measurement. Limb ischemia can be assessed by examining the toe brachial index (TBI) using the Vascular Doppler instrument. The TBI is measured on a scale where a value greater than 0.7 mmHg is considered normal, a value between 0.4 and 0.7 mmHg is considered abnormal, and a value below 0.4 mmHg is considered severe. This examination allows for the evaluation of peripheral microcirculation and can help determine the extent of improvement in cases of limb ischemia.
    Comparison of topical ozone therapy and placebo groups for diabetic foot ulcer infection
    Comparing the reduction of infection on the surface of diabetic foot ulcers in the groups receiving topical ozone therapy versus those receiving placebo. The utilization of a scale questionnaire (WIFI) for measurement purposes. The reduction in infection was assessed using an ordinal scale that categorized the severity of infection as follows: no infection (0), mild cellulitis measuring 2cm, moderate cellulitis exceeding 2cm, and severe sepsis/systemic infection.

    Full Information

    First Posted
    July 12, 2023
    Last Updated
    July 28, 2023
    Sponsor
    Asmat Burhan
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05977309
    Brief Title
    Effect of Topical Ozone on The Healing Diabetic Foot Ulcer
    Official Title
    The Effect of Therapy Ozone Topical on The Healing Diabetic Foot Ulcer: A Triple-Blind Randomized Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 1, 2023 (Anticipated)
    Primary Completion Date
    August 15, 2023 (Anticipated)
    Study Completion Date
    August 30, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Asmat Burhan

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Wound Heal, Diabetic Foot Ulcer, Ozone
    Keywords
    ozone, wound healing, diabetic foot ulcer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    In five wound care clinics on Java Island, Indonesia, 430 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 Wagner 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.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    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.
    Allocation
    Randomized
    Enrollment
    430 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Effect of Topical Ozone on The Healing Diabetic Foot Ulcer
    Arm Type
    Experimental
    Arm Description
    The topical ozone therapy group received standard wound care with modern dressings every three days for thirty days.
    Arm Title
    Effect of Standart Wound Care on The Healing Diabetic Foot Ulcer
    Arm Type
    Placebo Comparator
    Arm Description
    The placebo group received standard wound care with modern dressings thrice weekly for thirty days.
    Intervention Type
    Device
    Intervention Name(s)
    Topical ozone therapy
    Other Intervention Name(s)
    ozone therapy
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Comparison of the effects of topical ozone therapy and placebo on the healing of diabetic foot ulcers.
    Description
    Comparing the healing of diabetic foot ulcers in the topical ozone therapy group with the control group. The dimensions of a wound can be assessed for wound-healing purposes by employing a photographic apparatus to quantify the length and width of the wound.
    Time Frame
    Analysis was performed at the Baseline, fifteen days after treatment began, and thirty days after treatment began.
    Secondary Outcome Measure Information:
    Title
    Comparison of ischemia to variations in skin oxygen levels by transcutaneous oxygenation (TcPO2) assessment of topical ozone therapy and placebo in diabetic foot ulcers
    Description
    Differences in epidermal oxygenation levels between diabetic foot ulcers treated with topical ozone therapy and those treated with ozone. The utilization of a scale questionnaire (WIFI) for measurement. The measurement of oxygen levels in the skin to assess ischemia can be conducted using transcutaneous oxygen (TcPO2) measurements, employing the PeriFlux 6000 instrument, which provides a measurement scale. In the context of blood pressure, the categorizations are as follows: normal blood pressure is defined as being greater than 45 mmHG, mild blood pressure falls within the range of 40-45 mmHg, moderate blood pressure ranges from 20-39 mmHg, severe blood pressure is within the range of 1-20 mmHg, and critical blood pressure is defined as being at 0 mmHg.
    Time Frame
    Analysis was performed at the Baseline, fifteen days after treatment began, and thirty days after treatment began.
    Title
    Comparison of improvement in peripheral microcirculation from ischemia in diabetic foot ulcers between topical ozone therapy and a control group using the toe ankle-brachial index (TBI) measurement.
    Description
    Comparing the improvement in peripheral microcirculation of the foot in diabetic foot ulcers treated with topical ozone versus those treated with ozone. The utilization of a scale questionnaire (WIFI) for measurement. Limb ischemia can be assessed by examining the toe brachial index (TBI) using the Vascular Doppler instrument. The TBI is measured on a scale where a value greater than 0.7 mmHg is considered normal, a value between 0.4 and 0.7 mmHg is considered abnormal, and a value below 0.4 mmHg is considered severe. This examination allows for the evaluation of peripheral microcirculation and can help determine the extent of improvement in cases of limb ischemia.
    Time Frame
    Analysis was performed at the Baseline, fifteen days after treatment began, and thirty days after treatment began.
    Title
    Comparison of topical ozone therapy and placebo groups for diabetic foot ulcer infection
    Description
    Comparing the reduction of infection on the surface of diabetic foot ulcers in the groups receiving topical ozone therapy versus those receiving placebo. The utilization of a scale questionnaire (WIFI) for measurement purposes. The reduction in infection was assessed using an ordinal scale that categorized the severity of infection as follows: no infection (0), mild cellulitis measuring 2cm, moderate cellulitis exceeding 2cm, and severe sepsis/systemic infection.
    Time Frame
    Analysis was performed at the Baseline, fifteen days after treatment began, and thirty days after treatment began

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion standarts: 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Asmat Burhan, MSN
    Phone
    +6285746157782
    Email
    asmatburhan@uhb.ac.id
    First Name & Middle Initial & Last Name or Official Title & Degree
    Septian Mixrova Sebayang, MSN
    Phone
    +628529721449
    Email
    septiansebayang@uhb.ac.id
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Asmat Burhan, MSN
    Organizational Affiliation
    Universitas of Harapan Bangsa
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Only participant data is utilised in this study.
    Links:
    URL
    https://doi.org/10.1016/j.dsx.2018.11.060
    Description
    Diabetic foot ulcer is one of the common complications of diabetes disease that is costly and difficult to treat.
    URL
    https://doi.org/10.1590/1677-5449.190070
    Description
    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").
    URL
    https://doi.org/10.2337/dc16-2042
    Description
    Diabetic neuropathies are the most prevalent chronic complications of diabetes.
    URL
    https://doi.org/10.4239/wjd.v13.i12.1106
    Description
    complication of diabetes mellitus and significant cause of mortality and morbidity.
    URL
    https://kesmas.kemkes.go.id/assets/upload/dir_519d41d8cd98f00/files/Hasil-riskesdas-2018_1274.pdf
    Description
    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%
    URL
    https://doi.org/10.1093/cid/cis346
    Description
    Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration.
    URL
    https://doi.org/10.1371/journal.pone.0239236
    Description
    DFU patients in the gangrenous stage have a high risk of amputation.
    URL
    http://doi.org/10.1007/s00203-020-01818-x
    Description
    DFU treatment costs the healthcare system and the patient's family a lot.
    URL
    https://doi.org/10.2147/TCRM.S255247
    Description
    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
    URL
    https://doi.org/10.3390/antiox11081553
    Description
    ozone administration can induce tolerance to oxidative stress and prevent free radical-mediated injury
    URL
    https://doi.org/10.1186/2045-9912-1-29
    Description
    ozone administration can induce tolerance to oxidative stress and prevent free radical-mediated injury
    URL
    https://doi.org/10.1155/2015/515042
    Description
    stimulate the endogenous antioxidant system, which may ultimately contribute to preventing cell neuropathy and enhanced perfusion and oxygenation of tissue
    URL
    https://doi.org/10.1016/j.amjms.2020.05.012
    Description
    Diabetic foot ulcer patients have a high mortality rate of almost 50% within 5 years with one of the causes being infection

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    Effect of Topical Ozone on The Healing Diabetic Foot Ulcer

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