Intermittent Negative Pressure to Improve Blood Flow in Patients With Peripheral Artery Disease: Effects After Long-term Treatment

Not Applicable

Completed

• Conditions: Intermittent Claudication; Peripheral Arterial Disease
• Interventions: Device: FlowOx

• Registration Number: NCT03640676
• Lead Sponsor: Oslo University Hospital

Brief Summary

Studies have shown that intermittent negative pressure (INP) can induce short-term increase in blood flow in the extremity in patients with peripheral artery disease (PAD). Case reports also have indicated that INP treatment has beneficial hemodynamic and clinical effects in patients with lower limb ischemia and hard to heal leg ulcers. However, the clinical and physiological effects of long-term INP treatment are not well documented and needs further investigation.

Detailed Description

A double-blinded randomized sham-controlled trial.

Otivio AS is the developer of FlowOx, a noninvasive CE marked device to increase blood flow to the lower extremity. The device acts as a pressure chamber sealed around the patient's lower leg, applying pulses of intermittent negative pressure and atmospheric pressure. The pressure pulses are generated by a control unit, alternating between removing air from- and venting the pressure chamber.

Preliminary tests indicate a significant increase in blood flow to the extremity during INP treatment at -40 mmHg, but a similar increase in blood flow was not detected during treatment INP treatment at -10 mmHg. Hence, treatment with -10 mmHg, may serve as a sham intervention, when evaluating the clinical and physiological effects of long-term INP treatment.

All patients will receive best medical treatment including advice for smoking cessation, dietary advice, and advice for physical exercise, and pharmacological treatment with statins and platelet inhibitors. Patients will be randomized into two groups, one group receiving INP treatment with a pressure of -10 mmHg, the other group receiving INP treatment with a pressure of -40 mmHg. Treatment will be conducted by the patient him/herself at home, one hour in the morning and one hour in the evening for 12 weeks.

Pain-free- and maximal walking distance, ankle-brachial index, arterial blood flow during application of INP, maximal blood flow, and biomarkers of inflammation and endothelial dysfunction will be registered at baseline and after 12 weeks to evaluate the effects of long-term INP treatment.

Study Timeline

• Study First Submitted: 2018-08-14
• Study First Submitted QC: 2018-08-20
• Study First Posted: 2018-08-21
• Study Start: 2019-01-14
• Primary Completion: 2019-12-23
• Study Completion: 2020-01-31
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-03
• Last Update Posted: 2020-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

• Ankle-Brachial Index < 0,9, and intermittent claudication

Exclusion Criteria

• Incapable to make an informed consent
• Inability to perform a treadmill test
• Inability to independently operate FlowOx
• Severe heart disease such as unstable angina pectoris, severe heart failure (NYHA IV), severe valve failure
• Severe COPD

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
INP -40mmHg	FlowOx	In addition to standard medical treatment, patient swill receive treatment with FlowOx, applying intermittent negative pressure of -40mmHg one hour in the morning and one hour in the evening at home for 12 weeks.
INP -10mmHg	FlowOx	In addition to standard medical treatment, patients will receive treatment with FlowOx, applying intermittent negative pressure of -10mmHg one hour in the morning and one hour in the evening at home for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change in maximal walking distance	At baseline and after 12 weeks of treatment	Treadmill test
Change in pain-free walking distance	At baseline and after 12 weeks of treatment	Treadmill test

Secondary Outcome Measures

Name	Time	Method
Changes in resting and maximal blood flow	At baseline and after 12 weeks	Strain-gauge plethysmography
Change in serum levels of markers of inflammation and endothelial dysfunction	At baseline and after 12 weeks	E-selectin, ICAM-I, IL1, IL-6, IL-8, TNF-alfa, TGF-beta, IL-10
Changes in arterial blood flow during application of INP	At baseline and after 12 weeks	Ultrasound
Changes in Ankle-Brachial Index	At baseline and after 12 weeks

Trial Locations

Locations (3)

Department of Vascular Surgery, St. Olavs Hospital; 🇳🇴 Trondheim, Norway

Department of Surgery, Section of Vascular and Thoracic surgery, Sykehuset Sørlandet; 🇳🇴 Kristiansand, Norway

Department of Vascular Surgery, Oslo University Hospital, Aker; 🇳🇴 Oslo, Norway