The FlowOx device for the treatment of peripheral artery disease: current status and future prospects

Figures & data

Figure 1. The FlowOx device for lower extremity intermittent negative pressure treatment. Intermittent negative pressure is generated in a pressure chamber sealed around the patient’s lower leg by a pump unit that is removing air from and venting the pressure chamber. Source: Otivio AS/Bastian Fjeld

Table 1. Completed studies of the physiological, clinical, and health-economic implications of FlowOx

Author	N	Study design	Study population	Main conclusion
Sundby et al. [9]	23	Experimental	Healthy subjects	INP of – 40 mmHg induced rhythmical fluctuations in blood flow and increased both arterial blood flow velocity and skin blood flow.
Sundby et al. [13]	4	Case report	Peripheral artery disease	INP treatment should be investigated further as a potential noninvasive treatment option for patients with peripheral arterial disease and hard-to-heal leg ulcers.
Sundby et al. [1]	20	Experimental	Peripheral artery disease	INP increases foot macro- and microcirculatory flow pulsatility. Application of INP resulted in increased mean arterial blood flow velocity.
Sundby et al. [6]	24	Experimental	Spinal cord injured	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.
Sundby et al. [7]	9	Clinical crossover pilot	Spinal cord injury and chronic lower limb ulcers	INP can be used as a home-based treatment for patients with SCI and chronic lower limb ulcers. Its efficacy should be tested in an adequately sized, randomized clinical trial.
Holder et al. [11]	15	Experimental	Healthy subjects	INP induce fluctuations in blood flow and shear rate that improve endothelial function. This may represent a hemodynamic stimulus that improve vascular health.
Hoel et al. [2]	16	Experimental	Peripheral artery disease	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.
Hoel et al. [16]	72	RCT	Peripheral artery disease and intermittent claudication	Treatment with −40 mmHg INP for one hour twice daily for 12 weeks increased PWD compared with sham treatment. For patients with baseline PWD < 200 m, treatment with −40 mmHg INP increased both PWD and MWD compared with sham treatment.
Ezeofor et al. [8]	62	Health-economic study	Peripheral artery disease	FlowOx therapy delivered as a single annual dose may be a cost-effective treatment for peripheral artery disease. It improved health outcomes and reduced treatment costs in this modeled cohort.
Hoel et al. submitted 2021	72	RCT	Peripheral artery disease and intermittent claudication	A significantly proportion of the patients had a reduction in vWF, and the concentration of vWF was significantly reduced after treatment with −40 mmHg INP for one hour twice daily for 12 weeks. This may indicate a beneficial effect on endothelial activation and endothelial injury.
Hoel et al. submitted 2021	10	Clinical follow-up trial	Peripheral artery disease and intermittent claudication	Both PWD and 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.

INP intermittent negative pressure; SCI spinal cord injury; RCT randomized controlled trial; PWD pain-free walking distance; MWD maximal walking distance; vWF von Willebrand factor.

Sundby OH, Hoiseth LO, Mathiesen I, et al. Application of intermittent negative pressure on the lower extremity and its effect on macro- and microcirculation in the foot of healthy volunteers. Physiol Rep. 2016Sep;4:17.

 Web of Science ®Google Scholar

Sundby OH, Hoiseth LO, Mathiesen I, et al. 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. Physiol Rep. 2016Oct;4:20.

 Web of Science ®Google Scholar

Sundby OH, Hoiseth LO, Mathiesen I, et al. The acute effects of lower limb intermittent negative pressure on foot macro- and microcirculation in patients with peripheral arterial disease. PLoS One. 2017;12(6):e0179001.

 PubMed Web of Science ®Google Scholar

Sundby OH, Hoiseth LO, Irgens I, et al. Intermittent negative pressure applied to the lower limb increases foot macrocirculatory and microcirculatory blood flow pulsatility in people with spinal cord injury. Spinal Cord. 2018 Apr;56(4):382–391. .

 PubMed Web of Science ®Google Scholar

Sundby ØH, Irgens I, Høiseth L, et al. Intermittent mild negative pressure applied to the lower limb in patients with spinal cord injury and chronic lower limb ulcers: a crossover pilot study. Spinal Cord. 2018 Apr;56(4):372–381. .

 PubMed Web of Science ®Google Scholar

Holder SM, Dawson EA, Á B, et al. Fluctuation in shear rate, with unaltered mean shear rate, improves brachial artery flow-mediated dilation in healthy, young men. J Appl Physiol. 2019 Jun 1;126(6):1687–1693. .

 PubMed Web of Science ®Google Scholar

Hoel H, Lø H, Sandbæk G, et al. The acute effects of different levels of intermittent negative pressure on peripheral circulation in patients with peripheral artery disease. Physiol Rep. 2019;7(20):e14241.

 PubMed Web of Science ®Google Scholar

Hoel H, Pettersen EM, Lø H, et al. A randomized controlled trial of treatment with intermittent negative pressure for intermittent claudication. J Vasc Surg. 2020. DOI:10.1016/j.jvs.2020.10.024.

 PubMedGoogle Scholar

Ezeofor V, Bray N, Bryning L, et al. Economic model to examine the cost-effectiveness of FlowOx home therapy compared to standard care in patients with peripheral artery disease. PLoS One. 2021;16(1):e0244851.

 PubMed Web of Science ®Google Scholar