Clinical trial NCT03640676: Intermittent Negative Pressure to Improve Blood Flow in Patients With Peripheral Artery Disease: Effects After Long-term Treatment
Official title: Intermittent Negative Pressure to Improve Blood Flow in Patients With Peripheral Artery Disease: Effects After Long-term Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Arterial Disease
Intermittent Claudication
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Otivio AS
First posted: 2018-08-21
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blinded randomized sham-controlled trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in maximal walking distance
timeFrame: At baseline and after 12 weeks of treatment
measure: Change in pain-free walking distance
timeFrame: At baseline and after 12 weeks of treatment
Secondary outcomes:
measure: Change in serum levels of markers of inflammation and endothelial dysfunction
timeFrame: At baseline and after 12 weeks
measure: Changes in resting and maximal blood flow
timeFrame: At baseline and after 12 weeks
measure: Changes in Ankle-Brachial Index
timeFrame: At baseline and after 12 weeks
measure: Changes in arterial blood flow during application of INP
timeFrame: At baseline and after 12 weeks
Other outcomes:
Locations:
city: Kristiansand
country: Norway
facility: Department of Surgery, Section of Vascular and Thoracic surgery, Sykehuset Sørlandet
city: Oslo
country: Norway
facility: Department of Vascular Surgery, Oslo University Hospital, Aker
city: Trondheim
country: Norway
facility: Department of Vascular Surgery, St. Olavs Hospital
Study officials:
affiliation: Deprtment of Vascular Diseases, Oslo University Hospital
name: Jonny Hisdal, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoel H, Pettersen EM, Hoiseth LO, Mathiesen I, Seternes A, Seljeflot I, Hisdal J. Effects of intermittent negative pressure treatment on circulating vascular biomarkers in patients with intermittent claudication. Vasc Med. 2021 Oct;26(5):489-496. doi: 10.1177/1358863X211007933. Epub 2021 May 13.