Effects of Non Contact Low Frequency Ultrasound in Healing Venous Leg Ulcers

IN-BALANCE VLU Inflammation, Bacteria, & Angiogenesis Effects in Launching Venous Leg Ulcer Healing

This trial is a prospective, randomized, controlled, multi-center study of subjects presenting with chronic lower extremity venous ulcers. The study will evaluate the safety and effectiveness of MIST Therapy® plus standard of care (MIST+SOC) compared to Standard of Care (SOC) alone in the treatment of lower extremity venous ulcers.

Study Overview

• Status: Completed
• Conditions: Venous Insufficiency; Venous Reflux; Lower Extremity Ulcer
• Intervention / Treatment: Device: MIST Therapy

Detailed Description

The study compared the treatment effect of non-contact low frequency ultrasound in addition to standard of care versus standard of care alone in healing chronic venous leg ulcers in subjects who had documented venous stasis and reflux. Subjects that were screened and met the major inclusion criteria received standardized treatment of 30 to 40 mmHg compression, moist wound healing dressings, and debridement for a two week run-in period. If their study ulcer did not decreased by greater than 30% they were eligible for randomization. The primary endpoint was wound area reduction after four (4) weeks of study treatment. The study was performed at 22 study centers. The study included two sub-studies: fluid and tissue analysis and a wound recidivism registry that are ongoing.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Weymouth, Massachusetts, United States, 02189
      • South Shore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Lower extremity full thickness venous ulcer of > 30 days duration
• Subject's wound must be between 4 cm² and 50 cm² at screening
• Documented ABI that is between 0.8 and 1.2 on the study limb or transcutaneous partial pressure oxygen (TcpO2) > 40 mmHG; or a toe pressure > 40 mmHG; or a Doppler waveform consistent with adequate flow in the foot (biphasic or triphasic waveforms) at time of screening
• Biopsy for wounds > 6 months duration
• Documented index wound etiology of venous stasis with reflux and /or incompetent valves

Exclusion Criteria:

• Index ulcer wound that is less than 1 cm in distance from another ulcer wound
• > 5 ulcers on the index leg
• Index ulcer wound has exposed tendons, ligaments, muscle, or bone
• Index ulcer wound presents with clinical signs of acute infection, suspected or known
• Subjects with evidence of osteomyelitis or cellulitis or gangrene in the study limb
• Subjects with amputation above a Trans Metatarsal Amputation (TMA) in the study limb
• Subjects with active malignancy on the study limb except non-melanoma skin cancer
• Index ulcer that is of arterial disease etiology
• Index ulcer of other primary etiology (ie. vasculitis, arterial, pyoderma)
• Subjects with planned vascular surgery, angioplasty or thrombolysis procedures within the study treatment phase
• Subjects with planned surgical procedure during the study treatment phase for the index wound including skin flap or skin graft
• Subjects within 6 weeks postoperatively of a vascular o skin graft procedure.
• Subject has had prior skin replacement, negative pressure therapy, or traditional ultrasound therapy applied to the index wound in the 14 days prior to screening
• Subject has had ultrasound treatment (including MIST Therapy) of the index wound.
• Subject has received growth factor therapy (e.g., autologous platelet-rich plasma gel, becaplermin, bilayered cell therapy, dermal substitute, extracellular matrix) within 14 days of screening date.
• Subject is currently receiving or has received radiation or chemotherapy within 3 months of randomization.
• Female subjects that are pregnant or refuse to utilize adequate contraceptive methods and are of childbearing age during the trial.
• Subject has one or more medical condition(s), uncontrolled diabetes (i.e. HbA1c > 12), renal, hepatic, hematologic, neurologic, or immune disease that in the opinion of the investigator would make the subject an inappropriate study candidate
• Subject's wound would require ultrasound near an electronic implant or prosthesis
• Subject is known to be suffering from a disorder or other situation that the subject or investigator feels would interfere with compliance or other study requirements
• Subject is currently enrolled or has been enrolled in the last 30 days in another investigational device or drug trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; 30 to 40 mmHg compression, dressing for moist wound healing environment, debridement as needed. Minimum of one treatment per week and up to 3 times per week per investigator discretion for 4 weeks
Experimental: SOC + Mist Therapy; 30 to 40 mmHg compression, dressing for moist wound healing environment, debridement as needed plus non-contract low frequency ultrasound 3 x per week for 4 weeks.	Device: MIST Therapy; Non-contact low frequency ultrasound therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Area Mean Percent Reduction	Compare between the treatment groups percent wound area reduction at four weeks of study treatment. H0: µMIST+SC -- µSC = 0 HA: µMIST+SC -- µSC ≠ 0 Where µ = percent reduction in wound size.	4 weeks post baseline visit (randomization visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heal Rates	Compare rate of wound closure between study arms for 12 weeks post randomization. Descriptive statistics as not a powered endpoint.	12 weeks post randomization
Change in Pain VAS Scores	Compare VAS Pain Scores between arms at baseline and 4 weeks post randomization Subjects indicate their pain level by drawing a mark on a 10 cm line on a visual analog scale (VAS) at randomization and 4 week post treatment visit. The left end of the line indicates "no pain" and the right end of line indicates "worst pain imaginable". VAS score is determined by using a ruler placed at 0 (left end of scale) and measuring the distance from zero to the patient's mark . The objective is to compare the change in VAS values in MIST+SC to SC alone. H0: The average change in pain level is not different between MIST and SC HA: The average change in pain level is different between MIST and SC H0: µMIST = µSC vs HA: µMIST ≠ µSC, Statistical Analysis. A repeated measures ANCOVA will be used to test for differences in change in VAS with an indicator variable to indicate treatment, any demographic variables which were significant in the baseline comparisons.	Baseline, 2 weeks and 4 weeks post randomization

Collaborators and Investigators

• Sponsor: Celleration, Inc.
• Investigators: Principal Investigator: Gary Gibbons, MD, South Shore Hospital; Principal Investigator: Vicki Driver, DPM, Providence RI

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: March 7, 2012
• First Submitted That Met QC Criteria: March 8, 2012
• First Posted (Estimate): March 9, 2012

Study Record Updates

• Last Update Posted (Estimate): July 30, 2015
• Last Update Submitted That Met QC Criteria: July 2, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Reflux; Venous Insufficiency; Lower Extremity Ulcer
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Leg Ulcer; Varicose Ulcer; Venous Insufficiency
• Other Study ID Numbers: IN-BALANCE VLU