Final Report Summary - PREVENTDFU (Device for prophylaxis and treatment of diabetic foot ulcers for hospital and home use)
Executive Summary:
FlowOx™; A Novel Device to Improve Blood Flow in Limbs with Reduced Peripheral Circulation
The PreventDFU project develops a novel device able to deliver oscillating negative pressure pulses (NPP) to the lower limb of patients with peripheral arterial occlusive disease (PAOD). Perform a pilot study to evaluate if the NPP improve blood flow to the skin of the limb of patients with PAOD grade 2 or 3 (Fontaine classification).
A Plexi- glass chamber allowing insertion of a leg with PeriFlux System 5000 laser Doppler probes was developed. Skin blood flow was measured on the calf, the foot and the toe. The study was approved by the Norwegian Regional Ethics Committee. Skin blood flow was measured before and during application of NPP (n= 8 patients). The NPP induced change in skin blood flow was calculated for each patient. Across all subjects, the statistical significance of the NPP induced change in skin blood flow was analyzed by performing two-sided paired Wilcoxon test.
A new device (FlowOx™) was developed which could be worn by patients with reduced peripheral circulation. The system consists of a rigid boot, with internal padding to prevent pressure points on the leg and skin. A silicone sleeve seals the device and allows for application of NPP. NPP consists of a pressure of -40 mmHg for 10 seconds and 7 seconds of atmospheric pressure. These oscillating negative pressure pulses induced an increase in skin blood flow of the toes of about 60% (n=8, P<0,05).
NPP applied by a FlowOx™ boot may be used to enhance skin blood flow of the toes in patients with reduced peripheral circulation. There is also a trend (not statistically significant) towards increased circulation in other skin areas. Further studies need to be carried out to evaluate the effect of NPP in patients with reduced peripheral circulation. It will be important to look at long term effects to understand implication for wound healing.
Project Context and Objectives:
The PreventDFU project has developed an advanced prototype for prophylaxis and treatment of diabetic foot ulcers (DFUs). This is a condition that contributes to morbidity and loss of Quality of Life (QoL) of Diabetes Mellitus sufferers. The project is based on a proprietary pulsating negative pressure technology and will result in a prototype to be used at home or in nursing homes, for treatment and prevention of DFUs.
The project will improve an already tested technology previously used to cool or heat patients. The goal of the current project was to modify existing devices into a new device called FlowOxTM. The device works by applying mild negative oscillating pressure pulses on the skin of a limb. This increases blood flow to the skin. The increased blood flow will improve oxygenation of the tissue and thereby prevent wounds to form and/or improve the healing process for chronic ulcers.
Project Results:
The project has made following key scientific and technological achievements in different work packages;
In WP1, a twofold study has been conducted. First, a detailed literature review has been carried out on several topics, all of them related to both a medical and a biomechanical point of view. Next, a series of users’ trials have been done to gain an insight into end users’ perspective about DFU treatments, problems and orthoses, as well as into what problems they encounter when using Ankel Foot Orthoses and how they conceive the orthosis to be designed. Afterwards, a detailed list of specifications of the product has been performed. This document forms the principal design input for the project, and is based on input from all partners of the PreventDFU project. Finally, a preliminary Risk Analysis has been performed in order to detect most important risks and possible actions to carry out in case of occurring during the development of the project.
In WP2, the main objective was to determine the optimum pressure regimen for an increase in blood flow to the lower extremities with pulsating negative pressure in patients with diabetes. The first task was to define the right patient cohort. Because the intended use of the FlowOx™ is to increase blood flow, the main patient cohort was patients with peripheral arterial occlusive disease (PAOD). These patients have decreased blood supply to the legs. Because diabetes is a substantial risk factor for PAOD, a proportion of PAOD patients also have diabetes. Thus, within the main patient cohort there could be patients with or without diabetes. Second, the application to the Regional Ethics committee was prepared and approval of the clinical trials was obtained. Finally, a series of clinical trials on optimization of skin blood flow and transcutaneous oxygentension with the pulsating negative pressure in patients with PAOD was done. Skin blood flow (Laser Doppler) and transcutaneous oxygentention was measured on the toe, foot and calf in 8 patients with PAOD (one with diabetes). Based on experience from healthy subjects, the study examined the effect of the basic cycle of 10 sec negative pressure followed by 7 sec atmospheric pressure, with 3 different negative pressure values, namely -40, -60 and -80 mm Hg. The results points to a statistical increase of more than 60% in skin blood flow in the toes during use of the -40 mmHg pressure regimen. There was no statistical difference recorded in the foot or the leg, nor was there any significant benefit using negative pressure of 60 or 80 mmHg. The pressure regimen of 10 sec negative pressure of -40 mmHg, followed by 7 sec atmospheric pressure was used in WP6 (validation of prototype).
In WP3, a system comprised of a boot, a base, paddings and a seal was developed which proved to be simple to put on and remove and comfortable to wear during treatment. Special attention was placed on reducing pressure points of the limb to eliminate the possibility of injury on already damaged or sensible tissue. The system was capable of holding the required vacuum and offered a good seal against the leg without producing excessive pressure to the skin.
The process for developing the device started by creating a series of conceptual models and sketched designs. Throughout a process of iteration and refinement a concept was selected and a series of CAD models were produced to further detail the design. A first model of the boot was prototyped and tried among several potential users to assess its ergonomic and usability potential. This first boot was also fitted with paddings, a seal and placed on a simple base; the fully functional system was tested and proved to be a solid concept that with a few modifications was to fulfil the product requirements.
For improving system usability and functionality, several biomechanical studies and anthropometric and user research were done. Results were used to obtain the optimal boot and component dimensions, position of the patient with respect to the boot and boot sizing. Based on the results of these studies, a second prototype was then produced, including also better quality paddings, seal and base. The system was tested and allowed to validate the design and to produce the final system with some modifications.
The final system was produced using high quality materials and proved to be practical to wear, fulfilled all the technical requirements and was safe to use.
In WP4, a bespoke PCB board and with customized software was produced to control the pneumatic system that delivered the required pressure treatment to the device. The system also allowed customizing the set up parameters, such as pressure and treatment length, and record all sessions within the treatment and produce reports.
The development process commenced by creating an outlined specification that then was translated into a “lab bench” demonstrator that was developed using a laptop and commercial software to run the pneumatic system. This approached allowed to quickly modify the system while it was being developed until the technical requirements were clearly defined. This system was used to control the two first prototypes for the boot.
Finally a bespoke PCB and additional electronics were developed along with its required software. The control and compliance system was able to fully control the device and all the pneumatics were packed in a small enclosure. Special attention was placed on using highly reliable components and ensuring that the device would always be safe to use.
In WP5, once all the components where produced and tested they were integrated into the fully working prototype that was to be used for the trials. The integrated system was verified and fully complied with all the requirements. It proved to be safe to use, practical to wear, achieved the required pressures, maintained records of all sessions and recorded any error if occurred.
In WP6, the main objective was to validate proper functioning of the prototype in up to 25 volunteers (preferably patients with PAOD, diabetes and wounds). First, the application to the Regional Ethics committee was prepared and approval of the clinical trial was obtained. Second, a clinical trial was done to evaluate whether the FlowOx™ device can deliver the correct negative pressure pulses (treatment) to the lower limb, and to determine whether the treatment with the FlowOx™ device increases leg blood flow. In addition, user-friendliness and safety was evaluated. 14 patients with PAOD were included in the study (3 with diabetes). None of the patients that chose to participate in the study had any leg ulcers. Arterial leg blood flow was measured with Ultrasound Doppler in the large arteries supplying the legs, instead of skin blood flow (laser Doppler) and transcutaneous oxygen tension. This was done because the probes and cables for skin blood flow and transcutaneous oxygen tension could not fit into the new FlowOx™ prototype. Additionally, the new prototype would have introduced motion artefacts and influenced the quality of these measurements. The FlowOx™ boot delivered vacuum cycles effectively. The boot sealed against the leg and the padding and boot shell functioned. Regarding the effect on arterial leg blood flow, there was no statistical difference between leg blood flow before and during treatment. Regarding user-friendliness, the results indicate that the device is comfortable and easy to use. There were no serious adverse events. A total of 7 adverse events were experienced by 5 patients. All were minor and recovered. None of the patients with PAOD and diabetes (n=3) showed an increase in leg blood flow when using the FlowOx™, which reflect the results for the total group of 14 patients. Based on these results and the results in Work Package 2, the FLowOx™ seem to be more directed towards increasing skin blood flow rather than increasing blood flow to the entire limb.
Potential Impact:
FlowOx technology belongs to global wound care management market which was valued at $14bn in 2009 and is forecast to reach $19.6bn in 2016 with a compound annual growth rate (CAGR) of 5%. The growth in this market is expected to be driven by the increasing prevalence of pressure ulcers, diabetic ulcers, venous ulcers and increasing patient awareness. [http://www.hospitalmanagement.net/features/feature97878]
The prevalence of peripheral arterial disease in the general population is 12–14%, affecting up to 20% of those over 70. Peripheral vascular disease affects 1 in 3 diabetics over the age of 50.
In the USA peripheral arterial disease affects 12–20 percent of Americans age 65 and older. Approximately 10 million Americans have PAD. Despite its prevalence and cardiovascular risk implications, only 25 percent of PAD patients are undergoing treatment.
According to Millennium Research Group, a global authority on medical technology market intelligence, increasing awareness and diagnosis of peripheral arterial disease (PAD) along with the introduction of improved next-generation devices will lead the United States peripheral vascular (PV) device market to grow strongly to reach $3.3 billion by 2017. Lower extremity treatment will grow substantially, as physicians and device manufacturers continue to focus on the prevention of limb amputation.
Although the wound healing market is large, multiple players and many different types of technologies, there are few, if any good solutions for chronic arterial ulcers. Surgery and interventional radiology are the most common option. The other device related system that has some effect is hyperbaric oxygen therapy (HBOT) where the patients is placed in a chamber with high concentration of oxygen at a high pressure. This requires the patient to visit a specialized facility for a couple of hours every day the treatment is ongoing (other for 6-8 weeks).
Currently, there is no dedicated solution for treatment and prophylaxis of arterial ulcers in the market and the sufferers rely on a range of generally ineffective methods such as massage, special dressings or herbal drugs that often provide temporary relief of suffering at the expense of worsening its underlying condition. The FlowOx solution will primarily help to restore a normal skin physiology enabling the body to fight infections in the skin and heal a wound. The underlying cause of an ulcer can be complex and very diverse, most wounds however will benefit from more oxygen, improved flow of nutrition and easier access to the wound area for the immune system.
It has been reported that diabetes sufferers have a 12 to 25% lifetime risk of developing peripheral arterial disease leading to arterial ulcers. According to the DiabetesAtlas.org over 55Mn Europeans in age group between 20 and 79 years of age are currently suffering from diabetes; over 30Mn of those belong to the age group between 60 and 79 years of age. The total World population of diabetes sufferers is around 371Mn (and around 110Mn of those belongs to the “elderly group” consisting of individuals between 60 and 79 years of age). The incidence of diabetes is expected to grow with the growth of aging population in Europe; estimates forecast between 1 and 1.5% annual growth for Europe and 2-3% for the Total World.
Considering diabetic arterials ulcers suffering population, if FlowOx technology can only help 5% of the ulcer sufferers, this would mean substantial QoL improvement for over 100,000 Europeans and over 1 Mn sufferers worldwide at any given time, substantially reduce associated healthcare costs and give a considerable boost to the European Medical Device Manufacturing, Nursing and Assisted Living sectors, while at the same time, provide a market of about €282Mn of this innovative technology.
List of Websites:
https://sites.google.com/site/preventdfu/home
FlowOx™; A Novel Device to Improve Blood Flow in Limbs with Reduced Peripheral Circulation
The PreventDFU project develops a novel device able to deliver oscillating negative pressure pulses (NPP) to the lower limb of patients with peripheral arterial occlusive disease (PAOD). Perform a pilot study to evaluate if the NPP improve blood flow to the skin of the limb of patients with PAOD grade 2 or 3 (Fontaine classification).
A Plexi- glass chamber allowing insertion of a leg with PeriFlux System 5000 laser Doppler probes was developed. Skin blood flow was measured on the calf, the foot and the toe. The study was approved by the Norwegian Regional Ethics Committee. Skin blood flow was measured before and during application of NPP (n= 8 patients). The NPP induced change in skin blood flow was calculated for each patient. Across all subjects, the statistical significance of the NPP induced change in skin blood flow was analyzed by performing two-sided paired Wilcoxon test.
A new device (FlowOx™) was developed which could be worn by patients with reduced peripheral circulation. The system consists of a rigid boot, with internal padding to prevent pressure points on the leg and skin. A silicone sleeve seals the device and allows for application of NPP. NPP consists of a pressure of -40 mmHg for 10 seconds and 7 seconds of atmospheric pressure. These oscillating negative pressure pulses induced an increase in skin blood flow of the toes of about 60% (n=8, P<0,05).
NPP applied by a FlowOx™ boot may be used to enhance skin blood flow of the toes in patients with reduced peripheral circulation. There is also a trend (not statistically significant) towards increased circulation in other skin areas. Further studies need to be carried out to evaluate the effect of NPP in patients with reduced peripheral circulation. It will be important to look at long term effects to understand implication for wound healing.
Project Context and Objectives:
The PreventDFU project has developed an advanced prototype for prophylaxis and treatment of diabetic foot ulcers (DFUs). This is a condition that contributes to morbidity and loss of Quality of Life (QoL) of Diabetes Mellitus sufferers. The project is based on a proprietary pulsating negative pressure technology and will result in a prototype to be used at home or in nursing homes, for treatment and prevention of DFUs.
The project will improve an already tested technology previously used to cool or heat patients. The goal of the current project was to modify existing devices into a new device called FlowOxTM. The device works by applying mild negative oscillating pressure pulses on the skin of a limb. This increases blood flow to the skin. The increased blood flow will improve oxygenation of the tissue and thereby prevent wounds to form and/or improve the healing process for chronic ulcers.
Project Results:
The project has made following key scientific and technological achievements in different work packages;
In WP1, a twofold study has been conducted. First, a detailed literature review has been carried out on several topics, all of them related to both a medical and a biomechanical point of view. Next, a series of users’ trials have been done to gain an insight into end users’ perspective about DFU treatments, problems and orthoses, as well as into what problems they encounter when using Ankel Foot Orthoses and how they conceive the orthosis to be designed. Afterwards, a detailed list of specifications of the product has been performed. This document forms the principal design input for the project, and is based on input from all partners of the PreventDFU project. Finally, a preliminary Risk Analysis has been performed in order to detect most important risks and possible actions to carry out in case of occurring during the development of the project.
In WP2, the main objective was to determine the optimum pressure regimen for an increase in blood flow to the lower extremities with pulsating negative pressure in patients with diabetes. The first task was to define the right patient cohort. Because the intended use of the FlowOx™ is to increase blood flow, the main patient cohort was patients with peripheral arterial occlusive disease (PAOD). These patients have decreased blood supply to the legs. Because diabetes is a substantial risk factor for PAOD, a proportion of PAOD patients also have diabetes. Thus, within the main patient cohort there could be patients with or without diabetes. Second, the application to the Regional Ethics committee was prepared and approval of the clinical trials was obtained. Finally, a series of clinical trials on optimization of skin blood flow and transcutaneous oxygentension with the pulsating negative pressure in patients with PAOD was done. Skin blood flow (Laser Doppler) and transcutaneous oxygentention was measured on the toe, foot and calf in 8 patients with PAOD (one with diabetes). Based on experience from healthy subjects, the study examined the effect of the basic cycle of 10 sec negative pressure followed by 7 sec atmospheric pressure, with 3 different negative pressure values, namely -40, -60 and -80 mm Hg. The results points to a statistical increase of more than 60% in skin blood flow in the toes during use of the -40 mmHg pressure regimen. There was no statistical difference recorded in the foot or the leg, nor was there any significant benefit using negative pressure of 60 or 80 mmHg. The pressure regimen of 10 sec negative pressure of -40 mmHg, followed by 7 sec atmospheric pressure was used in WP6 (validation of prototype).
In WP3, a system comprised of a boot, a base, paddings and a seal was developed which proved to be simple to put on and remove and comfortable to wear during treatment. Special attention was placed on reducing pressure points of the limb to eliminate the possibility of injury on already damaged or sensible tissue. The system was capable of holding the required vacuum and offered a good seal against the leg without producing excessive pressure to the skin.
The process for developing the device started by creating a series of conceptual models and sketched designs. Throughout a process of iteration and refinement a concept was selected and a series of CAD models were produced to further detail the design. A first model of the boot was prototyped and tried among several potential users to assess its ergonomic and usability potential. This first boot was also fitted with paddings, a seal and placed on a simple base; the fully functional system was tested and proved to be a solid concept that with a few modifications was to fulfil the product requirements.
For improving system usability and functionality, several biomechanical studies and anthropometric and user research were done. Results were used to obtain the optimal boot and component dimensions, position of the patient with respect to the boot and boot sizing. Based on the results of these studies, a second prototype was then produced, including also better quality paddings, seal and base. The system was tested and allowed to validate the design and to produce the final system with some modifications.
The final system was produced using high quality materials and proved to be practical to wear, fulfilled all the technical requirements and was safe to use.
In WP4, a bespoke PCB board and with customized software was produced to control the pneumatic system that delivered the required pressure treatment to the device. The system also allowed customizing the set up parameters, such as pressure and treatment length, and record all sessions within the treatment and produce reports.
The development process commenced by creating an outlined specification that then was translated into a “lab bench” demonstrator that was developed using a laptop and commercial software to run the pneumatic system. This approached allowed to quickly modify the system while it was being developed until the technical requirements were clearly defined. This system was used to control the two first prototypes for the boot.
Finally a bespoke PCB and additional electronics were developed along with its required software. The control and compliance system was able to fully control the device and all the pneumatics were packed in a small enclosure. Special attention was placed on using highly reliable components and ensuring that the device would always be safe to use.
In WP5, once all the components where produced and tested they were integrated into the fully working prototype that was to be used for the trials. The integrated system was verified and fully complied with all the requirements. It proved to be safe to use, practical to wear, achieved the required pressures, maintained records of all sessions and recorded any error if occurred.
In WP6, the main objective was to validate proper functioning of the prototype in up to 25 volunteers (preferably patients with PAOD, diabetes and wounds). First, the application to the Regional Ethics committee was prepared and approval of the clinical trial was obtained. Second, a clinical trial was done to evaluate whether the FlowOx™ device can deliver the correct negative pressure pulses (treatment) to the lower limb, and to determine whether the treatment with the FlowOx™ device increases leg blood flow. In addition, user-friendliness and safety was evaluated. 14 patients with PAOD were included in the study (3 with diabetes). None of the patients that chose to participate in the study had any leg ulcers. Arterial leg blood flow was measured with Ultrasound Doppler in the large arteries supplying the legs, instead of skin blood flow (laser Doppler) and transcutaneous oxygen tension. This was done because the probes and cables for skin blood flow and transcutaneous oxygen tension could not fit into the new FlowOx™ prototype. Additionally, the new prototype would have introduced motion artefacts and influenced the quality of these measurements. The FlowOx™ boot delivered vacuum cycles effectively. The boot sealed against the leg and the padding and boot shell functioned. Regarding the effect on arterial leg blood flow, there was no statistical difference between leg blood flow before and during treatment. Regarding user-friendliness, the results indicate that the device is comfortable and easy to use. There were no serious adverse events. A total of 7 adverse events were experienced by 5 patients. All were minor and recovered. None of the patients with PAOD and diabetes (n=3) showed an increase in leg blood flow when using the FlowOx™, which reflect the results for the total group of 14 patients. Based on these results and the results in Work Package 2, the FLowOx™ seem to be more directed towards increasing skin blood flow rather than increasing blood flow to the entire limb.
Potential Impact:
FlowOx technology belongs to global wound care management market which was valued at $14bn in 2009 and is forecast to reach $19.6bn in 2016 with a compound annual growth rate (CAGR) of 5%. The growth in this market is expected to be driven by the increasing prevalence of pressure ulcers, diabetic ulcers, venous ulcers and increasing patient awareness. [http://www.hospitalmanagement.net/features/feature97878]
The prevalence of peripheral arterial disease in the general population is 12–14%, affecting up to 20% of those over 70. Peripheral vascular disease affects 1 in 3 diabetics over the age of 50.
In the USA peripheral arterial disease affects 12–20 percent of Americans age 65 and older. Approximately 10 million Americans have PAD. Despite its prevalence and cardiovascular risk implications, only 25 percent of PAD patients are undergoing treatment.
According to Millennium Research Group, a global authority on medical technology market intelligence, increasing awareness and diagnosis of peripheral arterial disease (PAD) along with the introduction of improved next-generation devices will lead the United States peripheral vascular (PV) device market to grow strongly to reach $3.3 billion by 2017. Lower extremity treatment will grow substantially, as physicians and device manufacturers continue to focus on the prevention of limb amputation.
Although the wound healing market is large, multiple players and many different types of technologies, there are few, if any good solutions for chronic arterial ulcers. Surgery and interventional radiology are the most common option. The other device related system that has some effect is hyperbaric oxygen therapy (HBOT) where the patients is placed in a chamber with high concentration of oxygen at a high pressure. This requires the patient to visit a specialized facility for a couple of hours every day the treatment is ongoing (other for 6-8 weeks).
Currently, there is no dedicated solution for treatment and prophylaxis of arterial ulcers in the market and the sufferers rely on a range of generally ineffective methods such as massage, special dressings or herbal drugs that often provide temporary relief of suffering at the expense of worsening its underlying condition. The FlowOx solution will primarily help to restore a normal skin physiology enabling the body to fight infections in the skin and heal a wound. The underlying cause of an ulcer can be complex and very diverse, most wounds however will benefit from more oxygen, improved flow of nutrition and easier access to the wound area for the immune system.
It has been reported that diabetes sufferers have a 12 to 25% lifetime risk of developing peripheral arterial disease leading to arterial ulcers. According to the DiabetesAtlas.org over 55Mn Europeans in age group between 20 and 79 years of age are currently suffering from diabetes; over 30Mn of those belong to the age group between 60 and 79 years of age. The total World population of diabetes sufferers is around 371Mn (and around 110Mn of those belongs to the “elderly group” consisting of individuals between 60 and 79 years of age). The incidence of diabetes is expected to grow with the growth of aging population in Europe; estimates forecast between 1 and 1.5% annual growth for Europe and 2-3% for the Total World.
Considering diabetic arterials ulcers suffering population, if FlowOx technology can only help 5% of the ulcer sufferers, this would mean substantial QoL improvement for over 100,000 Europeans and over 1 Mn sufferers worldwide at any given time, substantially reduce associated healthcare costs and give a considerable boost to the European Medical Device Manufacturing, Nursing and Assisted Living sectors, while at the same time, provide a market of about €282Mn of this innovative technology.
List of Websites:
https://sites.google.com/site/preventdfu/home