What is peripheral artery disease (PAD)?
Peripheral artery disease, also called peripheral arterial disease (PAD), is a common circulatory problem in which narrowed arteries reduce blood flow to the limbs. When developing (PAD), the extremities — usually the legs — do not receive enough blood flow to keep up with demand.
Overview on published clinical data on FlowOx™
Circulatory effects – Mode of Action:
The effect of 12-week treatment with intermittent negative pressure on blood flow velocity and flowmotion, measured with a novel doppler device (Earlybird). Secondary outcomes from a randomized sham-controlled trial in patients with peripheral arterial disease (PAD)
Study conclusion:
Earlybird is an applicable tool for assessing blood flow velocity in patients with PAD. Analysis of the flow velocity recordings shows that INP induces an immediate increase in blood flow velocities during INP. The positive effects of INP may be attributed to recruitment of arterioles, and thereby, increasing blood flow. In these analyses, no flow characteristics were determined which could predict who would benefit INP treatment.
Author: Pettersen et. al. 2022. Download publication here!
Application of intermittent negative pressure on the lower extremity and its effect on macro- and microcirculation in the foot of healthy volunteers
Study conclusion:
The first study to describe the effects of INP on skin blood flow and arterial blood flow velocity. The first to compare different sequences of negative pressure oscillations on lower limb perfusion. This study found that application of frequent mild intermittent negative pressure (INP) of -40 mmHg in the foot in healthy volunteers induced rhythmical fluctuations in blood flow and increased both arterial blood flow velocity and skin blood flow.
Author: Sundby et. al. 2016. Download publication here!
The acute effects of different levels of intermittent negative pressure on peripheral circulation in patients with peripheral artery disease
Study conclusion:
INP of -40 and -60 mmHg applied in cycles of 10 sec of negative pressure and 7 sec of atmospheric pressure induced acute increase in arterial and skin blood flow.
Author: Hoel et. al. 2019. Download publication here!
The acute effects of lower limb intermittent negative pressure on foot macro- and microcirculation in patients with peripheral arterial disease
Study conclusion:
INP of -40 and -60 mmHg applied in cycles of 10 sec of negative pressure and 7 sec of atmospheric pressure induced acute increase in arterial and skin blood flow.
Author: Hoel et. al. 2019. Download publication here!
The acute effects of lower limb intermittent negative pressure on foot macro- and microcirculation in patients with peripheral arterial disease
Study conclusion:
INP increases foot macro- and microcirculatory flow pulsatility. Application of INP resulted in increased mean arterial blood flow velocity.
Author: Sundby et. al. 2017. Download publication here!
Intermittent negative pressure applied to the lower limb increases foot macrocirculatory and microcirculatory blood flow pulsatility in people with spinal cord injury
Study conclusion:
INP induced an increase in arterial blood flow in the foot, followed by a decrease. This fluctuation was observed following the onset of negative pressure, without any significant changes in heart rate or mean arterial pressure.
This INP-induced increase in blood flow pulsatility during short oscillations of negative pressure may potentially promote tissue perfusion and ulcer healing in people with spinal cord injuries and ulcers in the lower limb.
Author: Sundby et. al. 2017. Download publication here!
Fluctuation in shear rate, with unaltered mean shear rate, improves brachial artery flow-mediated dilation in healthy, young men
Study conclusion:
INP induce fluctuations in blood flow and shear rate that improve endothelial function. This may represent a hemodynamic stimulus that improve vascular health.
Author: Holder et. al. 2019. Download publication here!
Impact on primary clinical endpoints:
A randomized controlled trial of treatment with intermittent negative pressure for intermittent claudication
Study conclusion:
Treatment with -40 mmHg INP for one hour twice daily for 12 weeks increased pain free walking distance (PWD) compared with sham treatment. For patients with baseline PWD <200 m, treatment with -40 mmHg INP increased both PWD and maximal walking distance (MWD) compared with sham treatment.
Author: Hoel et. al. 2020. Download publication here!
Intermittent negative pressure for Intermittent Claudication – 24 week follow up
Study conclusion:
Both pain free walking distance (PWD) and maximal walking distance (MWD) improved after treatment with –40 mmHg INP for one hour twice daily for 24 weeks compared with baseline. The main improvement in PWD occurred during the first 12 weeks of treatment, whereas the main improvement in MWD occurred between 12 and 24 weeks of treatment.
Author: Hoel et al. submitted 2021. Download publication here!
Effects of intermittent negative pressure treatment on circulating vascular biomarkers in patients with intermittent claudication
Study conclusion:
In this randomized controlled trial of patients with IC, there were no significant differences in the change in circulating levels of VCAM-1, ICAM-1, E-selectin, P-selectin, vWF, L-arginine, ADMA, and SDMA after treatment with –40 mmHg INP for 1 hour twice daily for 12 weeks, compared with sham treatment. However, a significantly larger proportion of the patients in the treatment group had a reduction in vWF compared with the sham control group, and the concentration of vWF was significantly reduced within the treatment group after 12 weeks, which might indicate a beneficial effect of INP treatment on endothelial activation and endothelial injury.
Author: Hoel et al. submitted 2021. Download publication here!
Intermittent negative pressure (INP) therapy in patients with no-option chronic limb-threatening ischemia
Study conclusion:
INP therapy in no-option CLTI patients showed a significant improvement of the skin perfusion after 6 weeks.
Therefore, INP therapy might have therapeutic potential in these critical ill patients.
A statistical increase of the ABI was recognized.
In addition to the objective measurements of skin perfusion and ABI, from a clinical perspective the patients reported a statistically significant reduction in self reported rest-pain.
Author: S. Yagshyyev et al., INP therapy in no-option CLTI. 2023. Download publication here!
Impact on treatment of key symptoms:
The effects of intermittent negative pressure on the lower extremities’ peripheral circulation and wound healing in four patients with lower limb ischemia and hard‐to‐heal leg ulcers: a case report
Study conclusion:
In these cases, involving patients with hard-to-heal leg and foot ulcers, observed that INP therapy improved ulcer healing considerably. Foot perfusion improved after completion of 8 weeks of INP-therapy.
Author: Sundby et. al. 2016. Download publication here!
Intermittent mild negative pressure applied to the lower limb in patients with spinal cord injury and chronic lower limb ulcers: a crossover pilot study
Study conclusion:
INP can be used as a home-based treatment for patients with SCI and chronic lower limb ulcers.
Author: Sundby et. al. 2018. Download publication here!
Health Economic Considerations:
Economic model to examine the cost-effectiveness of FlowOx home therapy compared to standard care in patients with peripheral artery disease
Study conclusion:
FlowOx™ therapy may be a cost-effective treatment for peripheral artery disease. It improved health outcomes and reduced treatment costs in this modeled cohort.
Author: Ezeofor et al., 2021. Download publication here!
Review Articles:
The FlowOx™ device for the treatment of peripheral artery disease – current status and future prospect
Study conclusion:
FlowOx™ treatment increases walking capacity and may be a useful adjunct to standard care for patients with disabling intermittent claudication.
Observational data indicate a positive effect in selected patients with critical limb ischemia not amenable for revascularization. Treatment with FlowOx™ seems safe for patients with PAD and has few side effects. The system offers a new tool for the treatment of PAD, it enables patients to treat themselves at home.
Author: Hoel & Hisdal, 2021. Download publication here!
Patient and Clinician experiences and opinions of the use of a novel home use medical device in the treatment of peripheral vascular disease – a qualitative study
Study conclusion:
Patients and clinicians were positive about the device due to its ease of use. PAD patients experienced significantly more benefit, especially for ischemic ulceration than those with a chronic venous condition.
FlowOx™ demonstrates potential as a conservative therapy offering users a convenient, home use, self-care management solution for improving symptomatic PAD and quality of life (QoL).
Author: Sedgwick et al., 2021. Download publication here!
Pulsating negative pressure
Skin Blood Flow in a foot during FlowOx™ treatment
The video shows the live Doppler signal measuring blood flow velocity in a small artery in the foot (arteria dorsalis pedis). The recording is done on a patient with reduced peripheral circulation. Six seconds into the recording the negative pressure is applied for 10 second followed by a 7 second period of normal pressure. The sequence is repeated with the negative pressure starting again after 23 seconds and 40 seconds.
FlowOx™ is indicated for the treatment of
- Peripheral arterial disease
- Diabetic and non-diabetic arteriopathic foot and leg ulcers
- Intermittent claudication and rest pain
- Foot and lower leg ulcers of mixed aetiology and/or pain/spasticity or discomfort associated with immobility such as paraplegia following spinal cord injury or other neurodegenerative diseases such as multiple sclerosis.
Listen to Stine’s and Hans Thomas’ stories
Stine’s story with FlowOx™
FlowOx™ first patient, Hans Thomas