Lymphedema
Conditions
Keywords
lymphedema, pneumatic compression device, randomised clinical trial, volume reduction
Brief summary
The treatment of lymphedema has been a major focus of attention for physicians and scientists for several decades. At this time, no successful techniques have been developed to prevent lymphedema, and therefore, a great deal of emphasis is placed on treatment modalities that can lessen the severity and impede the progression of this debilitating condition. The treatment on offer usually consists of a maintenance phase using compression garments and an intensive treatment phase, which includes the use of skin care, compression bandaging, exercise and manual lymphatic drainage (MLD). The intensive phase is usually described as complex decongestive therapy (CDT). This is time consuming and requires high resource usage. Pneumatic compression devices (PCD) offer and alternative to MLD and can be used by the patient. There are a number of devices on the market that are categorized into 1. without calibrated gradient compression 2. With calibrated gradient compression. This trial will compare two PCDs, a simple device without calibrated compression, and an advanced device with calibrated compression, in the reduction of swelling and maintenance of reduced limb volume in 262 patients with lower limb lymphoedema. The primary end point will be limb volume reduction over 12 weeks of treatment, with secondary outcome after 24 weeks.
Detailed description
This is a Multicentre, prospective, single (assessor) blind randomised study. The primary objective of the study is to assess volume reduction in the treatment of lymphoedematous legs with an advanced PCD compared to a simple PCD in patients with lower limb lymphoedema. The main outcome is the percentage volume reduction of the affected limb at end of treatment compared to baseline. Secondary objectives of the study are Assessment of safety Quality of life Health economic parameters In total 262 patients with leg lymphoedema will be enrolled into the study. Patients eligible for the study are those who suffer from late stage II and stage III according to the International Society of Lymphology lymphoedema staging. Lymphoedematous legs can be of primary or secondary origin and uni or bilaterally affected. Medical history will be taken at baseline. Patients will be taught how to use the device they have been randomised to. Visits will then take place at weeks 1,4,8,12 and 24 weeks. The device will be used for up to 60 minutes each day on the trial limb. At each visit sequential circumferences of the affected and unaffected limbs will be measured with a tape measure. All adverse events will be documented. At beginning and end of study quality of life questionnaires and health economic information will be completed by the patients. At the Derby site assessment of tissue quality will be made using ultrasound and moisture meter to assess tissue fluid.
Interventions
DEVICEFlexitouch System
A segmental, programmable, gradient pneumatic compression device. It consists of a controller and garment set. The garments are constructed of nylon and have 27-32 chambers, depending upon garment size. The pressure setting is variable between normal and increased. The device is intended to be used for 60 minutes per day
DEVICEHydroven FPR
The FH is an intermittent sequential external pneumatic compression system. The garment contains 3 compression chambers. The pressure range of the compressor device is 30-100 mmHg. It is intended to be used for 60 minutes per day.
Sponsors
Tactile Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be ≥ 18 years old or legal age in host country. * Subjects must have a diagnosis of primary or secondary late Stage 2 or 3 unilateral or bilateral lower extremity lymphoedema. * At time of initial evaluation, individuals must be at least 3 months post-surgery, chemotherapy and/or radiation treatment for cancer if applicable. * If subjects were treated in a clinic setting for lymphoedema (Phase 1 treatment) they must be at least 3 months post completion of their acute care.
Exclusion criteria
* Diagnosis of active or recurrent cancer, or less than 3 months at the time of initial evaluation from the completion of chemotherapy, radiation therapy or primary surgery for the treatment of cancer. * Diagnosis of acute infection. The source of the infection must be treated for 2 weeks prior to admittance into the study. * Diagnosis of acute thrombophlebitis (in last 2 months) * Diagnosis of peripheral arterial disease (PAD): PAD is defined as an Ankle Brachial Index (ABI), of 0.7 or lower. * Diagnosis of pulmonary embolism or deep vein thrombosis within the previous 6 months * Diagnosis of pulmonary edema * Diagnosis of congestive heart failure (uncontrolled) * Diagnosis of chronic kidney disease with a Glomerular Filtration Rate (GFR) of less than 30 mls per minute. * Patients with poorly controlled asthma (i.e. those with severe persistent symptoms throughout the day, night time awakenings several times per week, use of a beta2 agonist inhaler several times per day and those whose normal activity is extremely limited). * Pregnancy * Any condition where increased venous and lymphatic return is undesirable * Inability or unwillingness to participate in all aspects of study protocol and/or inability to provide informed consent * Currently participating in another clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Baseline to 12 weeks was the primary outcome; other time points included for informational purposes. | Limb volume in ml as assessed using the tape measure method of collecting circumferential leg measurements to insert into the truncated cone formula for limb volume calculation. A positive score indicates volume reduction between baseline and the noted follow-up, while a negative score indicates volume increase. |
| Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Baseline to 12 weeks was the primary outcome; other time points included for informational purposes. | Limb volume (percent change from baseline) as assessed using the tape measure method of collecting circumferential leg measurements to insert into the truncated cone formula for limb volume calculation. A positive score indicates volume reduction between baseline and the noted follow-up, while a negative score indicates volume increase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events - Totals | Up to 24 weeks of treatment | Adverse and serious adverse events will be recorded for patients for the duration of their participation in the trial |
Countries
Australia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Advanced PCD The use of an advanced PCD device to reduce and maintain limb volume
Flexitouch System: A segmental, programmable, gradient pneumatic compression device. It consists of a controller and garment set. The garments are constructed of nylon and have 27-32 chambers, depending upon garment size. The pressure setting is variable between normal and increased. The device is intended to be used for 60 minutes per day. | 64 |
| Simple PCD The use of the Simple PCD is to reduce and maintain limb volume
Hydroven FPR: The FH is an intermittent sequential external pneumatic compression system. The garment contains 3 compression chambers. The pressure range of the compressor device is 30-100 mmHg. It is intended to be used for 60 minutes per day. | 66 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Early Termination Due to Study Closure | 0 | 1 | 6 |
| Overall Study | Lost to Follow-up | 3 | 5 | 0 |
| Overall Study | Physician Decision | 5 | 7 | 2 |
| Overall Study | Withdrawal by Subject | 17 | 6 | 2 |
Baseline characteristics
| Characteristic | Advanced PCD | Simple PCD | Total |
|---|---|---|---|
| Age, Customized < 65 years | 47 Participants | 43 Participants | 90 Participants |
| Age, Customized ≥ 65 years | 17 Participants | 23 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 64 Participants | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Etiology of Lymphedema Primary | 34 Participants | 34 Participants | 68 Participants |
| Etiology of Lymphedema Secondary | 30 Participants | 32 Participants | 62 Participants |
| Hosiery Used No | 17 Participants | 18 Participants | 35 Participants |
| Hosiery Used Yes | 47 Participants | 48 Participants | 95 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 59 Participants | 61 Participants | 120 Participants |
| Region of Enrollment United Kingdom | 51 participants | 54 participants | 105 participants |
| Region of Enrollment United States | 13 participants | 12 participants | 25 participants |
| Severity of Lymphedema Late Stage II | 59 Participants | 61 Participants | 120 Participants |
| Severity of Lymphedema Stage III | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 47 Participants | 52 Participants | 99 Participants |
| Sex: Female, Male Male | 17 Participants | 14 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 66 |
| other Total, other adverse events | 25 / 64 | 15 / 66 |
| serious Total, serious adverse events | 3 / 64 | 3 / 66 |
Outcome results
Primary
Limb Volume Change Baseline to 12 Weeks of Treatment - Percent
Limb volume (percent change from baseline) as assessed using the tape measure method of collecting circumferential leg measurements to insert into the truncated cone formula for limb volume calculation. A positive score indicates volume reduction between baseline and the noted follow-up, while a negative score indicates volume increase.
Time frame: Baseline to 12 weeks was the primary outcome; other time points included for informational purposes.
Population: Of the 238 patients started in Participant Flow, 64 APCD and 66 SPCD had reached the 12 week visit milestone at the time of the outcome analysis. Results presented include 130 subjects who had completed the 12 week follow up (or who withdrew within 12 weeks) prior to the 26Oct2011 dataset. Data analyzed for subjects with measures assessed at the noted timepoint. Subjects who missed visits or who did not complete the assessment at the visit were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Advanced PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 1-Week | -0.4 percent change from baseline | Standard Deviation 6.2 |
| Advanced PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 4-Week | -0.1 percent change from baseline | Standard Deviation 6.3 |
| Advanced PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 8-Week | 0.2 percent change from baseline | Standard Deviation 7.4 |
| Advanced PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 12-Week | 0.6 percent change from baseline | Standard Deviation 6.4 |
| Simple PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 12-Week | 2.2 percent change from baseline | Standard Deviation 7.6 |
| Simple PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 1-Week | 0.9 percent change from baseline | Standard Deviation 5.8 |
| Simple PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 8-Week | 1.6 percent change from baseline | Standard Deviation 6.8 |
| Simple PCD | Limb Volume Change Baseline to 12 Weeks of Treatment - Percent | Change Baseline to 4-Week | 0.9 percent change from baseline | Standard Deviation 5.9 |
Primary
Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml
Limb volume in ml as assessed using the tape measure method of collecting circumferential leg measurements to insert into the truncated cone formula for limb volume calculation. A positive score indicates volume reduction between baseline and the noted follow-up, while a negative score indicates volume increase.
Time frame: Baseline to 12 weeks was the primary outcome; other time points included for informational purposes.
Population: Of the 238 patients started in Participant Flow, 64 APCD and 66 SPCD had reached the 12 week visit milestone at the time of the outcome analysis. Results presented include 130 subjects who had completed the 12 week follow up (or who withdrew within 12 weeks) prior to the 26Oct2011 dataset. Data analyzed for subjects with measures assessed at the noted timepoint. Subjects who missed a visit or who did not complete the assessment at the visit were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Advanced PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 1-Week | -11.1 ml | Standard Deviation 652.3 |
| Advanced PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 4-Week | 7.4 ml | Standard Deviation 636.3 |
| Advanced PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 8-Week | 77.7 ml | Standard Deviation 756.6 |
| Advanced PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 12-Week | 102.1 ml | Standard Deviation 724.5 |
| Simple PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 12-Week | 216.1 ml | Standard Deviation 919.3 |
| Simple PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 1-Week | 75.3 ml | Standard Deviation 678 |
| Simple PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 8-Week | 167.9 ml | Standard Deviation 760.7 |
| Simple PCD | Limb Volume Change Between Baseline and 12 Weeks of Treatment - ml | Change Baseline to 4-Week | 99.7 ml | Standard Deviation 691.3 |
Secondary
Adverse Events - Totals
Adverse and serious adverse events will be recorded for patients for the duration of their participation in the trial
Time frame: Up to 24 weeks of treatment
Population: Of the 238 patients started in Participant Flow, 64 APCD and 66 SPCD had reached the 12 week visit milestone at the time of the outcome analysis. Results presented include 130 subjects who had completed the 12 week follow up (or who withdrew within 12 weeks) prior to the 26Oct2011 dataset.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Advanced PCD | Adverse Events - Totals | Total Serious Adverse Events (SAE) | 3 number of events |
| Advanced PCD | Adverse Events - Totals | Device-Related SAE | 2 number of events |
| Advanced PCD | Adverse Events - Totals | Procedure-Related SAE | 0 number of events |
| Advanced PCD | Adverse Events - Totals | Unrelated SAE | 1 number of events |
| Advanced PCD | Adverse Events - Totals | Total Non-Serious Adverse Events (NSAE) | 34 number of events |
| Advanced PCD | Adverse Events - Totals | Device-Related NSAE | 13 number of events |
| Advanced PCD | Adverse Events - Totals | Procedure-Related NSAE | 12 number of events |
| Advanced PCD | Adverse Events - Totals | Unrelated NSAE | 9 number of events |
| Simple PCD | Adverse Events - Totals | Unrelated NSAE | 11 number of events |
| Simple PCD | Adverse Events - Totals | Total Serious Adverse Events (SAE) | 3 number of events |
| Simple PCD | Adverse Events - Totals | Total Non-Serious Adverse Events (NSAE) | 24 number of events |
| Simple PCD | Adverse Events - Totals | Device-Related SAE | 0 number of events |
| Simple PCD | Adverse Events - Totals | Procedure-Related NSAE | 5 number of events |
| Simple PCD | Adverse Events - Totals | Procedure-Related SAE | 1 number of events |
| Simple PCD | Adverse Events - Totals | Device-Related NSAE | 8 number of events |
| Simple PCD | Adverse Events - Totals | Unrelated SAE | 2 number of events |