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Trial registered on ANZCTR


Registration number
ACTRN12613001374752
Ethics application status
Approved
Date submitted
8/12/2013
Date registered
13/12/2013
Date last updated
12/01/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effectiveness of electrical stimulation and ultrasound in pressure ulcer treatment.
Scientific title
A randomized, controlled, clinical study on the effectiveness of high voltage pulsed current and high frequency ultrasound in treating pressure ulcers in geriatric patients
Secondary ID [1] 283717 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Physical therapy in wound healing
290680 0
Pressure ulcer treatment with high voltage pulsed current (HVPC) electrical stimulation
290681 0
Pressure ulcer treatment with high frequency ultrasound (HFUS) 290682 0
Condition category
Condition code
Physical Medicine / Rehabilitation 291047 291047 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Aim of study:

The research aimed to establish whether electrical stimulation (ES) with high voltage pulsed current (HVPC) and high frequency ultrasound (HFUS) can be effectively applied to promote the healing of stage II, III and IV pressure ulcers in geriatric patients , whether HVPC and HFUS help decrease wound surface area, and whether HVPC and HFUS have a significant effect on how fast wounds heal. The research involved a group of elderly patients (aged 60+) suffering from diseases typical of geriatric age. Their overall health state was, in most cases, poor, they were confined to bed and unable to change position on their own, and logical contact with them was very difficult or impossible.

Intervention:
Study enrollment. Patients with pressure ulcers screened for the study were residents of nursing and care centers in Silesia (Poland).
The study eligibility of a patient was determined by their physician. The eligibility criteria were the following: older than 60 years of age, a stage II, III or IV pressure ulcer of at least 0.5 cm2 located on the trunk, buttock region, lower and upper extremities, persisting for a minimum of 1 month but not longer than 12 months. If a patient had two pressure ulcers, both were evaluated for healing progress.
Patients with more than two pressure ulcers were not eligible to participate in the experiment. Other excluding criteria were neoplasm, lymphatic system diseases, central nervous system demyelinating diseases and cirrhosis of the liver. Patients with deep, tunneling, necrotic wounds likely to involve osteomyelitis and requiring surgical intervention were also excluded from the study.
Allocation to groups / randomization. After the selected patients, or their legal guardians, gave consent to take part in the study, they were randomly divided between three groups: a high-voltage pulsed current group (HVPC group), high-frequency ultrasound group (HFUS group) and a control group (CG). The main investigator in charge of patients’ allocation to groups had 100 envelopes, each containing a piece of paper marked with A (HFUS group), B (HFUS group) or C (control group). The envelopes were opened one by one in the presence of a physiotherapist and the patient concerned was directed to the appropriate comparative group.
The demographic information on the subjects was obtained from standardized interviews with the subjects, physical examinations, as well as from additional examinations of the patients and their history of concomitant diseases available in medical documentation.
Wound severity at enrolment was assessed according to the National and European Pressure Ulcer Advisory Panel criteria: partial-thickness loss of the dermis – stage II ulcers; full-thickness tissue loss – stage III pressure ulcers; full-thickness tissue loss with exposed bone, tendon or muscle - Stage IV pressure ulcer.
Treatment. All patients received treatment to prevent the development of additional pressure ulcers. Pressure-redistribution surfaces, devices and pillows were applied as needed. A physiotherapist or a nurse repositioned patients who could not move unaided at least every 2 hours. Those who could communicate logically and change position were asked to do so in order to relieve pressure affecting the ulcer area as often as they could.
Wounds were assessed throughout the period of the experiment to select topical treatments appropriately addressing moisture control, bacterial burden and debridement needs. A comprehensive, interdisciplinary assessment was conducted to develop an standard wound care (SWC) program taking account of the specific requirements of each subject, which included nutritional intervention, optimization of the wound dressing protocol, and continence management.
Patients in all groups received similar standard topical care, which was selected each time to address the needs of individual subjects and to promote moist interactive healing. Wounds were first cleansed with 0.9% sodium chloride, potassium permanganate or octenidine/phenoxyethanol, and then the ulcer base was covered with the dressing. Wound dressings included, regardless of the group, non-adherent gauze pads, dressings moistened with 0.9% sodium chloride, hydrogel, solcoseryl, and calendulae anthodia extractum. If wound debridement was needed or infection was suspected, fibrinolysin/deoxyribonuclease, colistinum and sulfathiazolum natricum (only in the control group) were additionally administered.
All immobilized patients received low-molecular-weight heparin (enoxaparin) as a standard therapy. Patients with elevated leukocyte levels were treated with antibiotics selected following the microbiological culture and sensitivity testing of pressure ulcers.
In all subjects that gave their consent to additional blood tests blood samples were collected at the beginning of the treatment period to determine: total protein, hemoglobin and hematocrit levels, and total lymphocyte count.

HVPC - group
Patients in group A additionally received electrical stimulation with HVPC. The device used for this purpose was the Intelect Advanced Combo (Chattanooga, USA). The voltage exceeded 50 V. Twin monophasic triangular pulses lasting 50 microseconds in total and having a frequency of 100 pps were applied. The amperage utilized during HVPC procedures evoked a tingling sensation in the patients, but no motor effects were induced. The electric charge equal to 2.5 - 7.5 micro-Coulombs per impulse (250-750 micro-Coulombs per second) was delivered to the treatment electrodes. Current characteristic were selected as per previously published protocols from clinical studies and in vivo studies performed on animals.
The electrodes were made of conductive carbon rubber. Each patient had his/her own set of electrodes. The treatment electrode was placed on an aseptic gauze pad saturated with physiological saline overlying the wound site. The dispersive electrode (closing the electric circuit) was positioned at least 20 cm from the pressure ulcer (proximally or distally, depending on its location). After each procedure, the electrodes were sterilized in a disinfectant solution.
Patients received five 50-minute procedures per week (one procedure per day). Treatment continued until healing or for a maximum of 6 weeks.
The cathode was introduced as the active electrode at the beginning of the treatment period to stimulate granulation tissue growth and then was replaced by the anode.
Before ES was applied, pressure ulcers were thoroughly cleansed with 0.9% sodium chloride solution. As soon as the procedure was complete, dressings mentioned were applied.

HFUS - group
The treatment B group was additionally administered HFUS. Its parameters were selected as per previously published protocols from clinical studies and in vivo studies performed on animals.
The acoustic beam was generated by the Intelect Advanced apparatus (Chatanooga Group, USA). The procedures were performed on the periwound and wound areas covered with sterile ultrasound gel (Aquasonic, Parker, USA). The effective radiating area (ERA) of the transducer was equal to 4.0cm2.
In the experiment, pulsed ultrasound of 1 MHz and a duty cycle of 20% (impulse time was equal to 2 ms and interval was equal to 8 ms) was used. The spatial average temporal peak (SATP) was equal to 0.5 W/cm2 and the spatial average temporal average (SATA) was equal to 0.1 W/cm2. The beam non-uniformity ratio was maximum 5:1.
Sonotherapy was applied for 1 min per cm2 of ulcer area (1 min per US probe area) in the first week, for 2 min per cm2 in the second week, and for 3 min per 1 cm2 between the third week and the end of the experiment. Sessions were held once a day, 5 days a week, over a period of 6 weeks.
Before and after each procedure the ultrasound transducer was sterilized in a disinfectant solution. Pressure ulcers were thoroughly cleansed with 0.9% sodium chloride solution in preparation of the procedure and then they were covered with the aforementioned dressings as soon as it was over.
Intervention code [1] 288407 0
Treatment: Devices
Intervention code [2] 288408 0
Treatment: Other
Intervention code [3] 288414 0
Rehabilitation
Comparator / control treatment
Patients in control group received standard treatment to prevent the development of additional pressure ulcers and standard wound care. Pressure-redistribution surfaces, devices and pillows were applied as needed. A physiotherapist or a nurse repositioned patients who could not move unaided at least every 2 hours. Those who could communicate logically and change position were asked to do so in order to relieve pressure affecting the ulcer area as often as they could.
Patients in control group received standard topical care, which was selected each time to address the needs of individual subjects and to promote moist interactive healing. Wounds were first cleansed with 0.9% sodium chloride, potassium permanganate or octenidine/phenoxyethanol, and then the ulcer base was covered with the dressing. Wound dressings included, regardless of the group, non-adherent gauze pads, dressings moistened with 0.9% sodium chloride, hydrogel, solcoseryl, and calendulae anthodia extractum. If wound debridement was needed or infection was suspected, fibrinolysin/deoxyribonuclease, colistinum and sulfathiazolum natricum (only in the control group) were additionally administered.
All immobilized patients received low-molecular-weight heparin (enoxaparin) as a standard therapy. Patients with elevated leukocyte levels were treated with antibiotics selected following the microbiological culture and sensitivity testing of pressure ulcers.
Control group
Active

Outcomes
Primary outcome [1] 291043 0
Each subject’s wound surface area (WSA; cm2), wound longest lengths (wound length (WL); cm) and wound longest (perpendicular) widths (wound width (WW); cm) were determined immediately before the experiment and then at the completion of each of the 6 weeks of treatment. In total, each subject’s pressure ulcers were measured 7 times.

Tests/Methods
Wound sizes were recorded by transferring their homothetic, congruent images onto transparent film sheets. The images showed wound perimeters and allowed wound lengths and widths to be measured with a centimeter ruler.

In order to determine pressure ulcer surface area the images were measured with a planimeter. Pressure ulcer area and perimeter were calculated with a digital set consisting of a digitizer (Mutoh Kurta XGT, Altek, USA) wired to a personal computer (C-GEO v. 4.0 Nadowski, PL), which was also used for storing the results. Pressure ulcers were additionally photographed.


Timepoint [1] 291043 0
At baseline, week 1, week 2, week 3, week 4, week 5, and week 6
Secondary outcome [1] 305994 0
After 6 weeks of treatment, percentage changes in wound surface area (WSA) and linear dimensions (wound length - WL and wound width - WW) were calculated according to formulas:

1) Change in WSA (%): S% = (Si – Sf) •100% /Si;
S% - change in wound size area (%)
Si – initial WSA (cm2)
Sf – final WSA (cm2);

2) Change in WL (%); L% = (Li – Lf ) •100% /Li;
L% - change in wound’s longest length (%),
Li – initial longest length (cm)
Lf – final longest length (cm)

3) Change in WW (%); W% = (Wi – Wf ) •100% /Wi;
W% - change in wound’s longest width (%),
Wi – initial longest width (cm)
Wf – final longest width (cm)

PUs that closed over that period were assigned a value of 100% decrease of wound surface area and they retained it during successive assessments as long as they remained closed.

The proportions of stage II, stage III and stage IV PUs that significantly improved (decreased by at least 50%), closed or worsened (their WSA exceeded its initial value) at the end of the intervention (at 6 week) was determined for each group.
Timepoint [1] 305994 0
At baseline and week 6

Eligibility
Key inclusion criteria
The eligibility criteria were the following: older than 60 years of age, a stage II, III or IV pressure ulcer of at least 0.5 cm2 located on the trunk, buttock region, lower and upper extremities, persisting for a minimum of 1 month but not longer than 12 months. If a patient had two pressure ulcers, both were evaluated for healing progress.
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with more than two pressure ulcers were not eligible to participate in the experiment. Other excluding criteria were neoplasm, lymphatic system diseases, central nervous system demyelinating diseases and cirrhosis of the liver. Patients with deep, tunneling, necrotic wounds likely to involve osteomyelitis and requiring surgical intervention were also excluded from the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The study eligibility of a patient was determined by their physician. After the selected patients, or their legal guardians, gave consent to take part in the study, they were randomly divided between three groups: a high-voltage pulsed current group (HVPC group), high-frequency ultrasound group (HFUS group) and a control group (CG). The main investigator in charge of patients’ allocation to groups had 100 envelopes, each containing a piece of paper marked with A (HFUS group), B (HFUS group) or C (control group). The envelopes were opened one by one in the presence of a physiotherapist and the patient concerned was directed to the appropriate comparative group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using numbered envelopes
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The homogeneity of distribution of patients’ characteristics was evaluated in all groups with the Fisher test for independence and Kruskal-Wallis test.
The relative and percentage changes in wound area, longest length and longest width were calculated. Mean wound areas, lengths, and widths were determined in each group before and after treatment and then were compared using the Wilcoxon matched pairs test.
The Kruskall-Wallis test and post-hoc T Tukey test served the purpose of comparing mean percentage changes in wound areas, longest lengths and longest widths.
The healing rates of stage II, III and IV wounds that significantly improved (decreasing by at least 50%), closed or worsened (their WSA exceeded its initial value) at the end of intervention (at 6 week) were calculated with the Fisher test.
The level of significance in all statistical tests performed due to the experiment was p less than 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5668 0
Poland
State/province [1] 5668 0
Silesia

Funding & Sponsors
Funding source category [1] 288392 0
University
Name [1] 288392 0
Academy of Physical Education
Address [1] 288392 0
Academy of Physical Education, Department of Physical Therapy
Mikolowska 72A street
40-065 Katowice, Poland
Country [1] 288392 0
Poland
Primary sponsor type
University
Name
Academy of Physical Education
Address
Academy of Physical Education; Department of Physical Therapy
Mikolowska 72A street
40-065 Katowice, Poland
Country
Poland
Secondary sponsor category [1] 287096 0
None
Name [1] 287096 0
Address [1] 287096 0
Country [1] 287096 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290278 0
The Research Ethics Committee from the Academy of Physical Education in Katowice, Poland
Ethics committee address [1] 290278 0
Mikolowska 72A street
40-065 Katowice
Ethics committee country [1] 290278 0
Poland
Date submitted for ethics approval [1] 290278 0
27/01/2010
Approval date [1] 290278 0
11/03/2010
Ethics approval number [1] 290278 0
10/2010 of 11 March 2010

Summary
Brief summary
Pressure ulcers are a serious condition that is particularly common among frail elderly people, making the development and implementation of effective therapies a pressing issue. In the case of pressure ulcer that resist standard wound care (SWC), the National and European Pressure Ulcer Advisory Panel guidelines (2009y) recommend the use of physical modalities, such as electrical stimulation, ultrasound, negative therapy, ultraviolet radiation and electromagnetic field.
The international guidelines recommend that clean recalcitrant stage III and IV pressure ulcers be treated with non-contact low frequency ultrasound spray (40 kHz). Low frequency ultrasound (LFUS) (22.5, 25, 35 kHz) is recommended as useful in the debridement of necrotic soft tissue (non-eschar) and high frequency ultrasound (HFUS) (MHz) as an adjunct in the treatment of infected pressure ulcers. It must be noted, however, that the recommendations are mainly based on expert opinions and indirect evidence (studies on humans with chronic wounds other than pressure ulcers and animal models). This means that sufficiently strong evidence from randomized clinical trials allowing a reliable evaluation of the therapeutic impact of US on the healing of human wounds, including pressure ulcers, is still to be provided.
The results of preclinical research show HFUS to stimulate cell membrane conductivity and increase cell calcium concentrations, which may result in increased activity of cells that are important for wounds to heal. HFUS stimulates the activity of macrophages and fibroblasts, activates collagen synthesis, increases the activity of cytokines and growth factors, as well as stimulating cell proliferation and angiogenesis. The results of in vivo studies with animals indicate that HFUS can promote wound healing regardless of their stage, whether inflammatory, proliferation, or remodeling. Following increasing intracellular concentrations of calcium ions the degranulation of mastocytes takes place and histamine, serotonin, heparin and other chemotactic factors are released; as a result, leukocytes and monocytes are being attracted to the damaged tissue and the migration of endothelial cells necessary in angiogenesis becomes easier.
There are only four clinical studies that evaluate ultrasound applied to pressure ulcers. Only one of them is a high quality randomized clinical trial, which was performed with 84 subjects. The other three suffer from many limitations. In one study the control group was not formed, another was a preliminary trial with only 5 patients, and in the third study sonotherapy was applied in conjunction with ultraviolet C radiation (UVC), so its effectiveness is difficult to determine. The ambiguity of the outcomes of studies on PUs makes it difficult to conclude on how efficacious HFUS can be as a modality promoting the pressure ulcers.
According to authors, electrical stimulation (ES) can be applied at different wound healing stages and it is used 1) to promote autolysis and/or reactivate the early inflammatory phase, 2) to promote the antibacterial effect, 3) to reactivate the anti-inflammatory effect, 4) to stimulate granulation tissue growth, and 5) to promote re-epithelialization. However, the precise rules for using ES in wound treatment are still to be established and confirmed in clinical research.
In vitro and in vivo studies have reported migration of cells involved in tissue repair toward the anode or cathode created by an electrical field delivered into a tissue culture. In cell cultures anode enhances motility of macrophages, and neutrophils, but human keratinocytes, fibroblasts and bovine corneal epithelial cells migrate directionally toward the cathode. In vivo studies have shown that the application of electric current significantly increases synthesis of adenosine triphosphate (five-fold) and protein (by 70%). ES of fibroblasts improves collagen synthesis. Studies have also shown that ES stimulates angiogenesis and improves blood flow. It is commonly recognized that cells involved in tissue repair require oxygen to function more efficiently. The results of studies in diabetic patients and in individuals with spinal cord injury (SPI) show that ES facilitates a temporary increase in local tissue oxygen tension.
National and European Pressure Ulcer Advisory Panels recommend electrical therapy for treating chronic and/or recurrent stage II, III and IV pressure ulcers. Kloth’s 2005 literature review also justified the use of electric charges for wound healing, particularly with respect to chronic wounds, where the natural low of bioelectric currents may be disturbed by tissue desiccation, residue from heavy metals (e.g. iodine, silver), the use of nonconductive petrolatum found in some impregnated dressings, and debriding enzymes. In those cases, ES can restore natural electric potentials and intensify healing processes.
A particularly promising therapeutic method in wound healing seems to be a high-voltage pulsed current (HVPC) electrical stimulation. A range of studies point to the efficacy of HVPC as a wound treatment modality, but its methodology has not been determined to date.
Trial website
Trial related presentations / publications
Polak A, Taradaj J, Nawrat-Szoltysik A, Stania M, Dolibog P, Blaszczak R, Zarzeczny R, Juras G, Franek A, Kucio C.

Reduction of pressure ulcer size with high-voltage pulsed current and high-frequency ultrasound: a randomised trial.

J Wound Care 2016 25(12):742-754

Public notes

Contacts
Principal investigator
Name 44810 0
Dr Anna Polak
Address 44810 0
Academy of Physical Education, Department of Physical Therapy
Mikolowska 72A street
40-065 Katowice
Country 44810 0
Poland
Phone 44810 0
+48608519262
Fax 44810 0
Email 44810 0
a.polak@awf.katowice.pl; polanna@op.pl
Contact person for public queries
Name 44811 0
Dr Anna Polak
Address 44811 0
Academy of Physical Education, Department of Physical Therapy
Mikolowska 72A street
40-065 Katowice
Country 44811 0
Poland
Phone 44811 0
+48608519262
Fax 44811 0
Email 44811 0
a.polak@awf.katowice.pl; polanna@op.pl
Contact person for scientific queries
Name 44812 0
Dr Anna Polak
Address 44812 0
Academy of Physical Education, Department of Physical Therapy
Mikolowska 72A street
40-065 Katowice
Country 44812 0
Poland
Phone 44812 0
+48608519262
Fax 44812 0
Email 44812 0
a.polak@awf.katowice.pl; polanna@op.pl

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Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary