Flexitouch Compression System for Venous Stasis Ulcer

• Sponsor: West Penn Allegheny Health System (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00534937
• Collaborator: The Cleveland Clinic (Other), Tactile Systems Technology, Inc. (Industry)
• Enrollment: 89
• Locations: 2
• Arms: 2
• Duration (Months): 39
• Patients Per Site: 44.5
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The researchers hypothesize that utilization of the Flexitouch system will improve the healing rates of (venous stasis ulcers) VSU compared to traditional compression wrapping therapy alone.

Primary Objective: The primary study objective is to determine whether the complete healing rate of venous stasis ulcers at 12 weeks is improved by the addition of Flexitouch® System compression therapy to a standard regimen of compression wrapping.

Secondary Objectives:

• To determine whether the addition of Flexitouch System compression therapy to a standard regimen of compression wrapping increases the percentage reduction in wound surface area.

• To determine whether the addition of Flexitouch compression therapy to a standard regimen of compression wrapping increases the percentage reduction in volume of the affected limb.

• To determine whether the addition of Flexitouch compression therapy to a standard regimen of compression wrapping decreases the time to healing of the venous stasis ulcer.

Condition or Disease	Intervention/Treatment	Phase
Venous Stasis Ulcer	Procedure: Compression wrapping; Procedure: Flexitouch compression pump	Phase 4

Detailed Description

Background:

Overview of venous stasis ulcers (1-3): Venous stasis ulceration is a common complication of venous insufficiency in the United States. Venous stasis ulcers (VSU) are associated with very significant morbidity, including patient disability, moderate to severe pain, and frequent leg infections. There is also a large cost associated with the medical care needed for this condition and the inability of patients to work. In some patients, this condition can be life- or limb-threatening.

Current standard of care for VSU: It is widely accepted that VSU should be treated by an individualized program of compression wrapping therapy (3-5). This therapy is designed to counteract the presumed pathophysiology of VSU, which develop as a result of valvular reflux and venous hypertension. However, the efficacy of compression therapy alone is suboptimal, with healing rates of roughly 34% reported after 12 weeks of therapy (6). Various adjunctive treatments have been studied, including artificial skin grafts (6-8). However, none of these adjunctive modalities have become widely accepted for the treatment of VSU.

Potential role of compression pumps: Intermittent sequential compression pumps are widely used as an adjunctive modality in the treatment of VSU. These pumps use high compression and are expensive, but this expense may be outweighed by improved healing of VSU. The use of compression pumps is consistent with the pathophysiology of VSU, but data regarding the efficacy of such therapy is scarce. To date, no study has adequately assessed the efficacy of compression pump therapy in the treatment of VSU (9).

Flexitouch System: The Flexitouch System was designed by a therapist trained in manual lymphatic drainage therapy and is produced by Tactile Systems Technology, Inc. The Flexitouch System was designed to simulate MLD techniques and is intended for home use during the self-management phase of CDT. MLD is one (of four) component(s) of Complete Decongestive Therapy, considered the "Gold Standard" for treatment of lymphedema. MLD is a gentle, manual technique producing very light directional pressure/stretch on the skin with manipulation of healthy lymph nodes and vessels. The effects of properly applied MLD include increased intake of lymphatic loads into the lymphatic system, increased lymphangiomotoricity, increased volume of transported lymph fluid, increased venous return in the superficial venous system, promotion of parasympathetic response and pain control. Treatment is always initiated at the trunk segments, with decongestion of proximal areas, prior to addressing the involved extremity (to clear central areas and promote decongestion of more distal areas). The extremity is then treated in segments, starting with the proximal segments and then progressing from distal to proximal regions. The Flexitouch® System is not intended to replace the intensive phase of CDT. However, it follows the principles of MLD in many ways. Flexitouch system provides limb treatment, but in addition, it addresses trunk congestion. The lower extremity garment set consists of two garments, one garment fits over the affected lower extremity and the other fits over the lower abdomen/trunk. Each garment is made up of multiple inflatable chambers within a flexible, stretchable fabric. The treatment consists of a 2-phase program. As in MLD, the preparation phase begins the treatment starting at the inguinal quadrant. Each curved trunk chamber inflates and deflates sequentially to facilitate the movement of edema fluid into the systemic circulation. The cycle is repeated several times. The inflation/deflation cycle is then repeated in each limb region from the knee to the groin, from the ankle to the knee, and finally from the toes to the ankle. The second phase, drainage, begins the sequential inflation/deflation cycle at the toes and continues moving up the leg to the quadrant of the trunk to facilitate the movement of edema fluid from the inguinal quadrant into the system circulation.

Choice of compression pump device for study of VSU treatment: A variety of inflatable compression pumps are available, but there are no data to help choose among these devices (9). No compression device is accepted as a standard of care for VSU. Flexitouch system differs from standard (intermittent sequential) compression pumps in significant ways. As described above, Flexitouch system is unique as a compression device, because it provides not only sequential limb compression, but also trunk compression. Flexitouch system's two-phase program (preparation and drainage) also makes it different from other compression devices. The fact that the system was created for lymphedema may be an advantage in the treatment of VSU, because many authors (10;11) believe that secondary lymphedema plays an important role among VSU patients.

Study Outline:

Patient enrollment procedure

• An approved consent form and authorization permitting release of personal health information must be signed by the patient or guardian.

• All eligibility requirements indicated in Section 3.0 must be satisfied.

• The patient must be registered by calling the study coordinator Lisa Rudman, at Allegheny General Hospital (412-359-4325).

General treatment plan: After enrollment, all patients will be seen once per week for a 12-week period for standard compression wrapping. At each visit, treatment and assessment will be undertaken as described below. The Flexitouch group only will use the Flexitouch System both at home (once daily) and in-clinic (once per week).

Essential elements of treatment and assessment:

Applicable to ALL patients

• The patients will be seen at the wound center one(1) times per week for 12 weeks.

• Patients will receive compression wrapping as standard of care therapy. The precise amount of compression will be individualized according to patient tolerance using 3M Coban 2 layer Compression System.

• The wound area will be measured and photographed weekly, using wound tracing and planimetry software.

• The limb volume will be measured weekly, using available software (NetHealth, Pittsburgh PA).

• The presence or absence of wound infection will be assessed. The need for wound debridement will be recorded.

• The wound will be scored as to whether or not it has healed. If the wound healed at a previous visit, the presence of recurrent ulceration will be assessed.

• The occurrence of treatment failure will be recorded (see section 7d).

• Comprehensive standard wound care treatment including gentle wound cleansing with saline solution at each visit, maintaining moisture balance in the wound and periwound with appropriate dressings (alginate, foam, hydrogel or hydrocolloid), reminding subjects of the importance of proper nutrition, leg elevation at rest and activity, including frequent ambulation and ankle ROM exercises through the day.

Additional steps applicable to patients randomized to Flexitouch arm:

• Patients will be provided a home Flexitouch unit. They will be given instructions to use the Flexitouch system on a once daily basis. They will not need remove the compression wrap for the home therapy.

• In addition to the home use, at each clinic visit, the patient's trunk and affected limb will be treated for 60 minutes with the Flexitouch system.

• The patient will be asked to indicate their level of comfort with the in-clinic Flexitouch session (scale of 0 to 5; 0 = very comfortable, 5 = very uncomfortable).

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Trial of the Flexitouch Compression System as an Adjunctive Treatment for Venous Stasis Ulcer
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard compression Patients in this arm will receive current standard of care (once-weekly short-stretch compression wrapping).	Procedure: Compression wrapping; Short-stretch compression wrap will be applied at least once a week.; Other Names: 3M short-stretch compression wrap
Experimental: Flexitouch Patients in this arm will receive once-a-week short stretch compression wrapping AND once-daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).	Procedure: Flexitouch compression pump; In addition to short-stretch wrapping, this group will received once-daily Flexitouch compression pump, both at home and during the once-a-week clinic visits.; Other Names: 3M compression wrap

Outcome Measures

Primary Outcome Measures

1. Complete Healing Rate of Venous Stasis Ulcers [12 weeks]

   Number of subjects that experience complete healing of the study venous stasis ulcer during the 12 week treatment period.

Secondary Outcome Measures

1. Change in Wound Surface Area for Non Healed Subject at 12 Weeks. [12 weeks]

   Change in wound surface area in cm2 from the initial screening to week 12 for all subject who did not completely healed before or at the 12 week visit.

2. Percentage Change in Volume of the Affected Limb (-Reduction; +Increase) [12 weeks]

3. Time to Healing of the Venous Stasis Ulcer [Baseline to 12 weeks]

   Only 2 time points so no calculation details are necessary. The change is calculated as the later time point minus the earlier time point (e.g., 12 weeks minus baseline).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• This study will enroll patients in a prospective manner with chronic venous insufficiency and venous stasis ulceration as determined from clinical presentation, positive venous reflux testing, or both.

• Patients must be 18 years old or more.

• The VSU size must be in the range 1-64 cm2.

• The ulcer must extend through both the epidermis and dermis, with no exposed tendon or bone.

• The VSU must have been present for more than 1 month.

• The ulcer must be located between and including the knee and ankle.

• The wound bed must have viable tissues with granulation tissue.

Exclusion Criteria:

• Exposed bone, tendon, or fascia.

• Severe rheumatoid arthritis.

• History of radiotherapy to the ulcer site.

• Uncontrolled congestive heart failure.

• Receiving corticosteroids or immune suppressives.

• History of collagen vascular disease.

• Known malnutrition (albumin < 2.5 g/dL). If malnutrition is suspected by the principal investigator, the albumin level should be checked to determine whether the patient meets the albumin criterion.

• Ulcer clinically infected at the time of entry into the study. However, patients may be entered into the study after successful treatment of infection.

• Known uncontrolled diabetes (HgbA1c > 12%). If the principal investigator suspects uncontrolled diabetes, the Hgb A1c should be checked to determine patient eligibility.

• Signs of cellulitis, osteomyelitis, or necrotic or avascular ulcer bed(s).

• Known arterial insufficiency (Ankle-brachial index < 0.7, or TCPO2 < 35 mmHg, or Toe brachial index < 0.4). If the principal investigator suspects uncontrolled diabetes, the Ankle-brachial index should be checked to determine patient eligibility.

• Active sickle cell disease.

• Unable to comply with the procedures described in the protocol.

• Enrolled in a clinical evaluation for another investigational wound-care device or drug.

• Patients diagnosed with deep venous thrombosis or phlebitis in the affected limb in the last 6 months.

• Pregnancy, suspected or confirmed.

• History of peripheral vascular disease, or chronic renal disease.

• Known active or recurrent cancer, or currently receiving chemotherapy or radiation therapy.

• History of pulmonary embolism.

• Poorly controlled asthma.

• Use of Apligraf, skin graft or similar biological dressing within 30 days of study entry.

• Patients with concurrent atrophie blanche.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195
2	Allegheny General Hospital Advanced Wound Healing and Lymphedema Center	Pittsburgh	Pennsylvania	United States	15212

Sponsors and Collaborators

• West Penn Allegheny Health System
• The Cleveland Clinic
• Tactile Systems Technology, Inc.

Investigators

• Principal Investigator: Satish Muluk, MD, West Penn Allegheny Health System

Study Documents (Full-Text)

None provided.

More Information

Publications

• Berliner E, Ozbilgin B, Zarin DA. A systematic review of pneumatic compression for treatment of chronic venous insufficiency and venous ulcers. J Vasc Surg. 2003 Mar;37(3):539-44. Review.
• Black SB. Venous stasis ulcers: a review. Ostomy Wound Manage. 1995 Sep;41(8):20-2, 24-6, 28-30 passim. Review.
• Falanga V, Sabolinski M. A bilayered living skin construct (APLIGRAF) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen. 1999 Jul-Aug;7(4):201-7.
• Felty CL, Rooke TW. Compression therapy for chronic venous insufficiency. Semin Vasc Surg. 2005 Mar;18(1):36-40. Review.
• Hansson C. Optimal treatment of venous (stasis) ulcers in elderly patients. Drugs Aging. 1994 Nov;5(5):323-34. Review.
• Kramer SA. Compression wraps for venous ulcer healing: a review. J Vasc Nurs. 1999 Dec;17(4):89-97; quiz 98-9. Review.
• Mostow EN, Haraway GD, Dalsing M, Hodde JP, King D; OASIS Venus Ulcer Study Group. Effectiveness of an extracellular matrix graft (OASIS Wound Matrix) in the treatment of chronic leg ulcers: a randomized clinical trial. J Vasc Surg. 2005 May;41(5):837-43.
• O'Donnell TF Jr, Lau J. A systematic review of randomized controlled trials of wound dressings for chronic venous ulcer. J Vasc Surg. 2006 Nov;44(5):1118-25. Review.
• Palfreyman SJ, Nelson EA, Lochiel R, Michaels JA. Dressings for healing venous leg ulcers. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD001103. Review. Update in: Cochrane Database Syst Rev. 2014;5:CD001103.
• Pascarella L, Schönbein GW, Bergan JJ. Microcirculation and venous ulcers: a review. Ann Vasc Surg. 2005 Nov;19(6):921-7. Review.
• Wollina U, Abdel-Naser MB, Mani R. A review of the microcirculation in skin in patients with chronic venous insufficiency: the problem and the evidence available for therapeutic options. Int J Low Extrem Wounds. 2006 Sep;5(3):169-80. Review.

• Responsible Party: Satish Muluk, Professor, Surgery, Temple University School of Medicine; Associate Professor, Cardiothoracic Surgery, Drexel University College of Medicine, West Penn Allegheny Health System
• ClinicalTrials.gov Identifier: NCT00534937
• Other Study ID Numbers: RC-4372
• First Posted: Sep 26, 2007
• Last Update Posted: Mar 1, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Satish Muluk, Professor, Surgery, Temple University School of Medicine; Associate Professor, Cardiothoracic Surgery, Drexel University College of Medicine, West Penn Allegheny Health System: Venous stasis ulcer; Compression pump; Randomized trial; Flexitouch compression
• Additional relevant MeSH terms: Varicose Ulcer; Ulcer

Study Results

Participant Flow

Recruitment Details	Recruitment occurred at medical clinics. The first subject was enrolled in November 2007. The subjects were recruited from current patient populations and new patients coming to the clinic. Advertisement materials were used to increase enrollment with little success.

Arm/Group Title	Standard Compression	Flexitouch
Arm/Group Description	Patients in this arm will receive current standard of care (once-weekly short-stretch compression wrapping).	Patients in this arm will receive once-a-week short stretch compression wrapping AND once daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).
Period Title: Overall Study
STARTED	42	47
COMPLETED	34	35
NOT COMPLETED	8	12

Baseline Characteristics

Arm/Group Title	Standard Compression	Flexitouch	Total
Arm/Group Description	Patients in this arm will receive current standard of care (once weekly short-stretch compression wrapping).	Patients in this arm will receive once-a-week short stretch compression wrapping AND once daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).	Total of all reporting groups
Overall Participants	42	47	89
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (14.3)	57.4 (16.1)	57.0 (15.2)
Sex/Gender, Customized (participants) [Number]
Female	11 26.2%	12 25.5%	23 25.8%
Male	28 66.7%	33 70.2%	61 68.5%
Unknown	3 7.1%	2 4.3%	5 5.6%

Outcome Measures

1. Primary Outcome

Title	Complete Healing Rate of Venous Stasis Ulcers
Description	Number of subjects that experience complete healing of the study venous stasis ulcer during the 12 week treatment period.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Compression	Flexitouch
Arm/Group Description	Patients in this arm received current standard of care (once weekly short-stretch compression wrapping).	Patients in this arm received once-a-week short stretch compression wrapping AND once-daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).
Measure Participants	42	47
Number [participants]	19 45.2%	20 42.6%

2. Secondary Outcome

Title	Change in Wound Surface Area for Non Healed Subject at 12 Weeks.
Description	Change in wound surface area in cm2 from the initial screening to week 12 for all subject who did not completely healed before or at the 12 week visit.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The participants are those that didn't achieve complete wound healing after 12 weeks of treatment. The change from screening to week 12 in wound surface area is reported.

Arm/Group Title	Standard Compression	Flexitouch
Arm/Group Description	Patients in this arm received current standard of care (once weekly short-stretch compression wrapping).	Patients in this arm received once-a-week short stretch compression wrapping AND once daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).
Measure Participants	17	15
Mean (Standard Deviation) [cm2]	-8.1 (9.8)	-9.6 (11.3)

3. Secondary Outcome

Title	Percentage Change in Volume of the Affected Limb (-Reduction; +Increase)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Number of participants who completed 12 weeks of treatment without healing. Also limb volume measures must have been present.

Arm/Group Title	Standard Compression	Flexitouch
Arm/Group Description	Patients in this arm received current standard of care (once weekly short-stretch compression wrapping).	Patients in this arm received once-a-week short stretch compression wrapping AND once-daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).
Measure Participants	17	16
Mean (Standard Deviation) [percentage of change]	-2.9 (34.1)	-7 (29.1)

4. Secondary Outcome

Title	Time to Healing of the Venous Stasis Ulcer
Description	Only 2 time points so no calculation details are necessary. The change is calculated as the later time point minus the earlier time point (e.g., 12 weeks minus baseline).
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Time to healing can only evaluate the patients that showed healing during the 12 week study therefore the number may not be consistent with other numbers.

Arm/Group Title	Standard Compression	Flexitouch
Arm/Group Description	Patients in this arm received current standard of care (once-weekly short-stretch compression wrapping).	Patients in this arm received once-a-week short stretch compression wrapping AND once-daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).
Measure Participants	19	20
Mean (Standard Deviation) [days]	37 (24.9)	43.9 (22.3)

Adverse Events

Time Frame	AEs were collected form 2007 to 2010 at the time of study closure.
Arm/Group Title	Standard Compression		Flexitouch
Arm/Group Description	Patients in this arm will receive current standard of care (once weekly short-stretch compression wrapping).		Patients in this arm will receive once-a-week short stretch compression wrapping AND once daily Flexitouch pump application (including Flexitouch application once-a-week in the clinic setting).
All Cause Mortality
	Standard Compression		Flexitouch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Compression		Flexitouch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/42 (7.1%)		0/47 (0%)
Infections and infestations
Cellulitis / Infection of lower extremity	3/42 (7.1%)	3	0/47 (0%)	0
Other (Not Including Serious) Adverse Events
	Standard Compression		Flexitouch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/42 (19%)		6/47 (12.8%)
Infections and infestations
Cellulitis / Infection of lower extremity	8/42 (19%)	8	6/47 (12.8%)	6

Limitations/Caveats

The study was terminated early due to lack of enrollment which ultimately lead to a limited number of subjects to include in an analysis.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.