Study of Healing Venous Leg Ulcers With Ultrasound Therapy

This study is currently recruiting participants.
Verified February 2014 by Celleration, Inc.
Sponsor:
Information provided by (Responsible Party):
Celleration, Inc.
ClinicalTrials.gov Identifier:
NCT01549860
First received: March 7, 2012
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

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® compared to Standard of Care (SOC) alone in the treatment of lower extremity venous ulcers.


Condition Intervention
Venous Insufficiency
Venous Reflux
Lower Extremity Ulcer
Device: MIST Therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: IN-BALANCE VLU Inflammation, Bacteria, & Angiogenesis Effects in Launching Venous Leg Ulcer Healing

Resource links provided by NLM:


Further study details as provided by Celleration, Inc.:

Primary Outcome Measures:
  • Wound Area Reduction [ Time Frame: 4 weeks post randomization ] [ Designated as safety issue: No ]

    Compare between the treatment groups percent wound area reduction at four weeks of study treatment.

    H0: µMIST -- µSOC = 0 HA: µMIST -- µSOC ≠ 0 Where µ = percent reduction in wound size.



Secondary Outcome Measures:
  • Time to heal [ Time Frame: 12 weeks post randomization ] [ Designated as safety issue: No ]

    Compare time to wound closure between study arms for 12 weeks post randomization

    H0: The time-to-closure of subjects in the MIST group through 12 weeks post randomization is equal to that in the SOC only group.

    HA: The time-to-closure of subjects in the MIST group with healed wounds through 12 weeks post randomization is not equal to that in the SOC only group.

    H0: SMIST = SSOC vs HA: SMIST ≠ SSOC

    Statistical Analysis The method of analysis of the time-to-closure data will be a Cox's regression analysis in which the response variable is wound closure (Y/N), and the independent variables for the analysis of wound closure during the treatment period are time of closure, treatment (SOC or MIST) and any demographic variables which were significant in the baseline comparisons.


  • Wound Recidivism Rates [ Time Frame: 12 Months Post Heal ] [ Designated as safety issue: No ]

    Time to wound re-opening for subjects that had wound healing by the end of the 4 week treatment period. Compare the rate of recidivism in the MIST+SOC group to that in the SOC only group. Will identify this recidivism as a "failure," thus "F" in hypothesis statement.

    H0: The time-to-recidivism of subjects in the MIST group through 12 months is equal to that in the SOC only group.

    HA: The time-to-recidivism of subjects in the MIST group with healed wounds through 12 months is not equal to that in the SOC only group.

    H0: FMIST = FSOC vs HA: FMIST ≠ FSOC Statistical Analysis The method of analysis of the time-to-recidivism data will be a Cox's regression analysis in which the response variable is recidivism (Y/N), and the independent variables are time of recidivism, treatment (SOC or MIST) and any demographic variables which were significant in the baseline comparisons.


  • Pain Level [ Time Frame: Baseline, 2 weeks and 4 weeks post randomization ] [ Designated as safety issue: No ]

    Compare VAS Pain Scores between arms at baseline, 2 weeks post treatment, and 4 weeks post randomization

    visual analog scale assessment collected at randomization, each weekly treatment visit, and first follow up visit. The objective is to compare the change in VAS values in MIST+SOC to SOC only.

    H0: The average change in pain level is not different between MIST and SOC HA: The average change in pain level is different between MIST and SOC H0: µMIST = µSOC vs HA: µMIST ≠ µSOC,

    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.


  • QOL [ Time Frame: Baseline and 4 Weeks post randomization ] [ Designated as safety issue: No ]

    Compare SF-36 and Cardiff Wound Impact Schedule between arms at baseline and 4 weeks post treatment

    The objective is to compare the change in QOL values in MIST+SOC to SOC only. H0: The average change in QOL is not different between MIST and SOC HA: The average change in QOL is different between MIST and SOC H0: µMIST = µSOC vs HA: µMIST ≠ µSOC,


  • Wound Area Reduction Stratified by Wound Age [ Time Frame: 4 weeks post randomization ] [ Designated as safety issue: No ]

    The secondary efficacy endpoint is percent reduction of wound area within stratifications of wound chronicity. The objective is to compare the percent reduction in wound area at 4 weeks in MIST+SOC to SOC only.

    H0: The wound age does not make a difference in wound healing at 4 weeks HA: The wound age makes a difference in wound healing at 4 weeks H0: βWOUND AGE = 0 vs HA: βWOUND AGE ≠ 0 Sample Size No sample size estimates were made for this objective because it is a secondary objective.

    Statistical Analysis An ANCOVA will be used to test for differences in change in percent reduction of wound area with an indicator variable to indicate treatment, an indicator covariate to indicate wound age, and any demographic variables which were significant in the baseline comparisons and adjust by the baseline wound area.


  • Wound Area Reduction Stratified by Wound Size [ Time Frame: 4 weeks post randomization ] [ Designated as safety issue: No ]

    The secondary efficacy endpoint is percent reduction of wound area. The objective is to compare the percent reduction in wound area at 4 weeks in MIST+SOC to SOC only.

    H0: The wound size does not impact wound healing at 4 weeks HA: The wound size impacts wound healing at 4 weeks H0: βWOUND SIZE = 0 vs HA: βWOUND SIZE ≠ 0 Sample Size No sample size estimates were made for this objective because it is a secondary objective.

    Statistical Analysis An ANCOVA will be used to test for differences in change in percent reduction of wound area with an indicator variable to indicate treatment, a covariate for the wound area at baseline, and any demographic variables which were significant in the baseline comparisons and adjust by the baseline wound area.



Other Outcome Measures:
  • Biomarker Analysis [ Time Frame: Baseline, 2 weeks and 4 weeks post randomization ] [ Designated as safety issue: No ]

    Compare between the treatment groups the effect of the assigned study treatment on cytokines, MMPs, TIMPs, fibrinogen, proteins, and other potential biomarkers as well as bacteria and angiogenesis properties in subjects who have consented for the fluid and tissue sub-study.

    These biomarkers endpoints are measured three times throughout the study. Each biomarker will be analyzed separately as described below.

    Analysis will include IL-1 β, IL-6, IL-8, IL-10, TNF α, VEGF, PDGF BB, FGF -2, PF4, TGFβ, MMP7, MMP9

    Statistical Analysis A repeated measures ANCOVA will be used to test for any differences in each biomarker or a transformation thereof (e.g., log transformation to bacteria counts) with an indicator variable to indicate treatment, and covariates for the use of artificial skin, the age of the wound, the size of the wound at baseline, and any demographic variables which were significant in the baseline comparisons.


  • Health Care Utilization [ Time Frame: 12 weeks post randomization ] [ Designated as safety issue: No ]

    Describe the overall treatments administered and quantify the cost of care to achieve wound closure and/or wound size reduction

    The endpoint of the this secondary objective is the cost of the healthcare treatments through 12 weeks. The objective is to compare the effect on the cost of treatment of the SOC and MIST treatments from the payer's perspective. NOTE: Payer costs are their reimbursements for healthcare services.

    H0: The cost in the MIST group is equal to that in the SOC only group. HA: The cost in the MIST group is not equal to that in the SOC only group. H0: MMIST = MSOC vs HA: MMIST ≠ MSOC


  • Bioengineer Skin Equivalents Utilization [ Time Frame: 12 weeks post randomization ] [ Designated as safety issue: No ]

    Compare the average number of bio-engineered skin equivalent applications in the SOC and MIST.

    H0: The number of applications in subjects in the MIST group through 12 weeks is equal to that in the SOC only group.

    HA: The number of applications in subjects in the MIST group with healed wounds through 12 weeks is not equal to that in the SOC only group.

    H0: NMIST = NSOC vs HA: NMIST ≠ NSOC



Estimated Enrollment: 208
Study Start Date: April 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Standard of Care
Current standard of care recommendations for the treatment of venous leg ulcers
Experimental: SOC + Mist Therapy
Current standard of care recommendations for the treatment of venous leg ulcers combined with the use of MIST Therapy
Device: MIST Therapy
Non-contact ultrasound therapy

Detailed Description:

The study will compare the effect of the assigned study treatments on wound area reduction at four (4) weeks of treatment. The study will be performed at up to 20 study centers. The study will include two sub-studies: fluid and tissue analysis and a wound recidivism registry.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Lower extremity full thickness venous ulcer of 30 to 364 days duration
  • Subject's wound must be between 10 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
  • 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
  • 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
  • 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 post-operatively 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 MIST Therapy treatment 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01549860

Contacts
Contact: Diane M Sahr, BSN dsahr@celleration.com

Locations
United States, Massachusetts
South Shore Hospital Recruiting
Weymouth, Massachusetts, United States, 02189
Contact: Gary Gibbons, MD    781-624-4950    gary_gibbons_md@sshosp.org   
Principal Investigator: Gary Gibbons, MD         
Sponsors and Collaborators
Celleration, Inc.
Investigators
Principal Investigator: Gary Gibbons, MD South Shore Hospital
Principal Investigator: Vicki Driver, DPM Providence RI
  More Information

No publications provided

Responsible Party: Celleration, Inc.
ClinicalTrials.gov Identifier: NCT01549860     History of Changes
Other Study ID Numbers: IN-BALANCE VLU
Study First Received: March 7, 2012
Last Updated: February 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Celleration, Inc.:
Venous Insufficiency
Reflux
Lower Extremity Ulcer

Additional relevant MeSH terms:
Leg Ulcer
Ulcer
Varicose Ulcer
Venous Insufficiency
Skin Ulcer
Skin Diseases
Pathologic Processes
Varicose Veins
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 17, 2014