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

Sponsor

Oslo University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03640676

Collaborator

Otivio AS (Industry)

Enrollment

Locations

Arms

12.6

Actual Duration (Months)

Patients Per Site

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease Intermittent Claudication	Device: FlowOx	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blinded randomized sham-controlled trialDouble-blinded randomized sham-controlled trial

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 14, 2019

Actual Primary Completion Date :

Dec 23, 2019

Actual Study Completion Date :

Jan 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: INP -10mmHg 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.	Device: FlowOx FlowOx is a CE marked device developed to increase blood flow to the lower extremities. A pressure chamber is sealed around the leg below the knee and is connected to a control unit which induces pulses of 10 sec negative pressure, and 7 sec of atmospheric pressure.
Active Comparator: INP -40mmHg 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.	Device: FlowOx FlowOx is a CE marked device developed to increase blood flow to the lower extremities. A pressure chamber is sealed around the leg below the knee and is connected to a control unit which induces pulses of 10 sec negative pressure, and 7 sec of atmospheric pressure.

Arm

Intervention/Treatment

Sham Comparator: INP -10mmHg

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.

Device: FlowOx

FlowOx is a CE marked device developed to increase blood flow to the lower extremities. A pressure chamber is sealed around the leg below the knee and is connected to a control unit which induces pulses of 10 sec negative pressure, and 7 sec of atmospheric pressure.

Active Comparator: INP -40mmHg

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.

Device: FlowOx

Outcome Measures

Primary Outcome Measures

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

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 resting and maximal blood flow [At baseline and after 12 weeks]
Strain-gauge plethysmography
Changes in Ankle-Brachial Index [At baseline and after 12 weeks]
Changes in arterial blood flow during application of INP [At baseline and after 12 weeks]
Ultrasound

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Department of Surgery, Section of Vascular and Thoracic surgery, Sykehuset Sørlandet	Kristiansand	Norway
2	Department of Vascular Surgery, Oslo University Hospital, Aker	Oslo	Norway
3	Department of Vascular Surgery, St. Olavs Hospital	Trondheim	Norway

Sponsors and Collaborators

Oslo University Hospital
Otivio AS

Investigators

Principal Investigator: Jonny Hisdal, PhD, Deprtment of Vascular Diseases, Oslo University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jonny Hisdal, Principal Investigator, Oslo University Hospital

ClinicalTrials.gov Identifier:

NCT03640676

Other Study ID Numbers:

2018/748

First Posted:

Aug 21, 2018

Last Update Posted:

Feb 5, 2020

Last Verified:

Feb 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Peripheral Arterial Disease

Peripheral Vascular Diseases

Intermittent Claudication

Study Results

No Results Posted as of Feb 5, 2020