Evaluation of a venous-return assist device to treat severe post-thrombotic syndrome (VENOPTS)

Abstract

Severe post-thrombotic syndrome (PTS) is responsible for considerable disability, reduced quality of life and increased health care costs. Current therapies are limited and often ineffective. We performed a two-centre, randomized, cross-over controlled trial to evaluate Venowave, a novel lower-limb venous-return assist device, for the treatment of severe PTS. Eligible subjects were allocated to receive, in randomized order, Venowave for eight weeks and a control device for eight weeks. The eight-week treatment periods were separated by a four-week period when no device was used (i.e. wash-out period). The primary outcome measure was a 'clinical success' defined as: i) reported benefit from the device; and ii) moderate or greater improvement in symptoms of PTS; and iii) willingness to continue using the device. Secondary outcome measures included quality of life (QOL) as measured by VEINES-QOL questionnaire (higher scores indicate better QOL), and PTS severity as measured by the Villalta PTS scale (higher scores indicate more severe PTS). The study was registered with Clinical Trials. gov (NCT00182208). Thirty-two patients were enrolled. Of these, 26 (80%) were also using graduated compression stockings. Twenty-six participants completed both trial periods. Clinical success occurred in 10 (31%) participants receiving Venowave and four (13%) participants receiving the control device, with two (6%) participants reporting a clinical success with both devices (P = 0.11). Mean VEINES-QOL score at the end of study period was significantly greater (P = 0.004) for Venowave (52.5; SD 5.8) compared to control (50.2; SD 6.2). Mean Villalta scale score at the end of study period was significantly decreased (P = 0.004) for Venowave (12.2; SD 6.3) compared to control (15.0; SD 6.1). In conclusion, Venowave appears to be a very promising new therapy for patients with severe PTS, which may be used alone or in combination with graduated compression stockings.

Full text

©2008 Schattauer GmbH,Stuttgart
623
Evaluation of avenous-return assistdevicetotreat severe
post-thromboticsyndrome (VENOPTS)
Arandomized controlledtrial
MartinJ.O’Donnell1,SimonMcRae1,Susan R. Kahn2,Jim A. Julian1,CliveKearon1,BetsyMacKinnon1,
Debbie Magier3,Carla Strulovich2,Theresa Lyons1,Sandra Robinson3,Jack Hirsh1,Jeffrey S. Ginsberg1,2
1Henderson Research Centre, McMaster University,Hamilton, Ontario,Canada; 2Centrefor Clinical Epidemiology and Community Studies,
Jewish General Hospital,Montreal, Québec,Canada; 3HamiltonHealth Sciences, Hamilton, Ontario,Canada
Summary
Severe post-thrombotic syndrome (PTS)isresponsible forcon-
siderabledisability,reduced quality of lifeand increasedhealth
carecosts. Currenttherapies arelimited and often ineffective.
We performedatwo-centre,randomized,cross-over controlled
trial to evaluate VenowaveTM,anovellower-limb venous-return
assist device,for thetreatment of severe PTS. Eligible subjects
were allocatedtoreceive,inrandomized order, Venowave for
eight weeks and acontroldevice foreight weeks.The eight-
week treatment periodswereseparatedbyafour-week period
whennodevice was used (i.e.wash-out period).The primary
outcome measurewas a‘clinical success’ defined as:i)reported
benefitfromthe device;and ii) moderate or greaterimprove-
ment in symptoms of PTS; andiii) willingness to continue using
the device.Secondaryoutcomemeasuresincluded quality of life
(QOL) as measured by VEINES-QOL questionnaire (higher
scores indicate better QOL), and PTSseverity as measured by
Keywords
Venous thrombosis,clinical studies,deep vein thrombosis
theVillalta PTSscale (higherscores indicate more severe PTS).
Thestudy was registeredwith ClinicalTrials.gov
(NCT00182208).Thirty-twopatientswereenrolled. Of these,
26 (80%) were also usinggraduatedcompression stockings.
Twenty-six participants completedboth trial periods. Clinical
success occurred in 10 (31%) participants receiving Venowave
and four (13%) participants receivingthe control device,with
two(6%)participantsreportingaclinical success with both de-
vices(P=0.11). Mean VEINES-QOL score at theend of study
periodwas significantlygreater(P=0.004) forVenowave (52.5;SD
5.8) compared to control (50.2;SD 6.2).MeanVillalta scale score
at theend of study periodwas significantlydecreased(P=0.004)
forVenowave (12.2; SD 6.3) compared to control (15.0; SD 6.1).
In conclusion,Venowave appearstobeavery promising newther-
apyfor patientswith severe PTS,which maybeusedalone or in
combinationwith graduated compression stockings.
ThrombHaemost 2008; 99: 623–629
NewTechnologies, DiagnosticTools andDrugs
Correspondence to:
Dr.MartinO’Donnell
Henderson ResearchCentre
70 Wing, Room 220
711Concession Street
Hamilton, Ontario,L8V 1C3, Canada
Te l.:+1 905 527 4322 (Ext. 44540),Fax:+1905 574 2646
E-mail: odonnm@mcmaster.ca
Financialsupport:
ThisProject wasfunded by an unrestrictedgrant from the InnovationsFoundation,
McMaster University (representing NSERC Intellectual Property Mobilization Group),
Hamilton, ON,Canada. Dr.Kearon and Dr O’Donnell aresupportedbythe Canadian
InstitutesofHealth Research. Dr.Kahn is arecipient of aClinicalInvestigator Award
from the FondsdelaRecherche en Santé du Québec.
ReceivedSeptember 6, 2007
Accepted after minor revision December5,2007
Prepublished onlineFebruary14, 2008
doi:10.1160/TH07-09-0546
Introduction
Post-thrombotic syndrome (PTS) is the most frequent chronic
complication of deep vein thrombosis (DVT) of the leg(1, 2).
Characterised by pain and swelling, it is responsiblefor consider-
able personal disability,reduced quality of lifeand substantial
health care costs (estimated at US $250 million per year in North
America) (3–8). Management of severe PTSpresents aparticu-
larchallenge to clinicians (5).The cornerstone of therapyis
graduated compression stockings whichhaveconsiderableclini-
cal limitations,inthat patients frequentlyexperienceonlypartial
or no symptom relief from stockings (5, 9–11). Although pneu-
matic compression pumps can provide symptomatic relief for
patients with severe PTS, theiruse is often impractical as pa-
tients must remainstationary for twohours or more per day, and
the expense of the pumps is oftenprohibitive (12).

O'Donnell et al.Novel device to treatpost-thromboticsyndrome
624
There is aneed to develop effectivetreatmentsfor severe PTS
that are well-tolerated and allow patients to carryonwith their
dailyactivities(6). In this clinicaltrial, we evaluate anovel de-
vice, Ve nowaveTM,for the treatment of severe PTS.
Methods
We performed arandomized placebo-controlled, double-blinded
'cross-over' trialofpatients with severe PTSattwo Clinical
Centres (Hamilton Health Sciences,ChedokeDivision,Hamil-
ton, Ontario; and the ThrombosisUnit, SirMortimer B. Davis
JewishGeneral Hospital, Montreal,Québec).The clinicaltrial
protocol wasapprovedbyHealth Canada (No. 64844) and the
Research and Ethics Boards of both Clinical Centres.The study
wasregistered with ClinicalTrials.gov (NCT00182208) and con-
ducted according to the ICH-Good Clinical Practiceguidelines
for clinicaltrials.
Intervention
Ve nowave is abattery-powered lowerlimb venous returnassist
devicedeveloped by Saringer Research Incorporated,Stouffvil-
le,ON, Canada (Fig. 1).Itconsistsofarotating motor coupled
with awave-generating linkage to aplanarplastic sheet,which is
placed longitudinallyonthe posterior aspect of the calf and gen-
eratesawave-formmotion on aflexible flat metalplatform. This
peristaltic pump (1 cm amplitude,8cmwide sinusoidal wave
moving at 2cm/sec) results in an upward,volumetric displace-
ment of the wave at 16 cc/sec. It is attached firmly aroundthe calf
with avelcro supportcuffand maybewornwhen mobile. The
cuffisadjustable to fitdifferent legsizes and can be adjustedto
accommodate changes in legswelling. Ve nowave is designed to
counteract venous stasis and venous hypertension, etiological
factorsresponsible for the development of PTS (13). In apre-
viousstudy of 10 subjectswith chronic limb edema, we demon-
stratedthat wearing Ve nowave for50minutes(min) produced an
88%increase in duplexultrasound-detected venous flowatthe
common femoralvein(p=0.03) (13).Inasubsequent open-label
pilot study (14),wedemonstrated that Ve nowave resultedina
substantial clinical improvement of symptoms in four of six sub-
jects with severe PTS(14).
All components of the control and active deviceswere ident-
ical,except for the connection betweenthe motor and the planar
sheetwas inactiveinthe control device.Therefore,the control
device wasidenticalinsize, weight and sound to the activeinter-
vention butdid not generate awaveform motion.The control de-
vice produced some calf compression through addedpressure
from the cuff, and wastherefore presentedtothe participants as
one of twoactiveinterventions and not as aplacebo.
Participants
Subjectsover18years of age with PTS were potentiallyeligible
if theyhad: i) aprevioushistoryofobjectively-documented deep
vein thrombosis; ii) dailyleg swelling with discomfort(i.e.re-
ported at leastone of the following symptoms: heavy legs, ac-
hing legs and/or throbbing) for aminimum of 6months that was
considereddue to PTS;and iii)Villalta scalescoreofgreater
than14(i.e.corresponds to severe PTS) (15).
Anypatients whohad: i) unstablesymptoms(worsening, im-
proving or variable over the previous month); ii) chronic lower
limb edemafrom causes other thandeep vein thrombosis; iii) ac-
tive venous ulceration; iv)baseline calfcircumference greater
than40cm(cuffistoo small); v) symptomatic peripheral arter-
ial disease; or vi) peripheral neuropathy, were excluded. Current
or prior useofgraduated compression stockings did not in-
fluence eligibility.
Eligible,consenting subjects were allocated randomly in a
1:1 ratiotofolloweitherSequence ‘A’(Ve nowave for8weeks in
Period 1followedbycontrol for 8weeks in Period 2), or Se-
quence ‘B’(control for 8weeks in Period 1followedbyVeno-
wave for8weeks in Period 2).At the end of Period 1, participants
hadafour-weekwash-outperiod beforestarting Period 2.
Devices were pre-packaged in pairswith each Ve nowave
paired with acontrol device.Paired devices were labeled“A” and
“B” corresponding to theorder of use, and notrelated to whether
theywere activeorcontrol. Random allocation wasdetermined
by consecutivelynumbered patient kits that contained encrypted
codes, corresponding to arandomly orderedpairofVe nowave or
control device. Upon obtaining writteninformed consent from
an eligible participant, the researchnurse openedthe next patient
kit in the sequence and provided the subjectwith deviceA.Par-
ticipants were provided with deviceBat the end of the wash-out
period.
All participants were instructedtoput the deviceoneach
morning andtowear it for most of the day, for the duration of the
studyperiod. Therewas no restriction (upperlimit) on the duration
of use. Subjectswereinformedthatthe devicecould be worn when
theywerestationaryormobile andweretaught howtouse the de-
Figure1:Venowave device. Unit size (without wraps) is 9cmx19cm
x4cm. Theunit weight is ~300 g(withwraps).

O'Donnell et al.Novel device to treatpost-thromboticsyndrome
625
vicei.e.method of application to leg, insertion of batteries,etc.
They were also giveninstructions on maintenanceofthe device,
andcontact numbers in the eventofamalfunction. Thedevicewas
to be worn onlyonthe legexhibiting the PTS (i.e.the indexleg).
Study subjects, investigatorsand researchnurseswere
blindedtotreatment allocation. To help maintain blinding, study
participants were assessed at differenttimestoeach other and
were asked nottodiscuss issuesrelating to the mechanical oper-
ation of the devicewith their clinicians. Both devices were called
‘Ve nodevice’rather than Ve nowave, to avoid potential insights
into the mechanism of action of the intervention.
Study measures
Four measurement instruments were used in this study. Aglobal
rating instrument wasusedtodetermine if each treatment phase
wasassociatedwith a‘clinical success’ (Fig. 2).Similaroutcome
measureshavebeen used in twopreviousrandomized trials in
subjectswith PTS (11,12). The Villalta scalewas used to
measurethe severity of PTS at baseline (inclusion criterion)and
follow-up, and wasasecondaryoutcome measure (15).This
scale wasdesignedtodiagnose and ratethe severity of PTS by
quantifying five symptoms and six signs and has been used fre-
quently in studiesofpatients with PTS. Higherscores indicate
moresevere PTSand ascoreofgreater than14corresponds to
severe PTS(maximum scoreof33) (15).Although both legs
were assessed,onlythe scores for the indexleg were used in the
analysis. TheVEINES-QOL questionnaire wasusedtomeasure
quality of life(QOL) (16). VEINES-QOL, avenous disease-spe-
cificquality of life instrument, hasbeen shown to be reliable and
responsivetochange over time in patients with PTS (16,17).
VEINES-Sym is avalidatedsubscale of VEINES-QOLthat
measuresseverity of venous symptoms. ForVEINES-QOL and
VEINES-Sym, higher scoresindicate better quality of life. At
study end,participants were asked if theypreferred the 'treat-
ment intervention' in Period 1orPeriod 2.
Data collection and follow-up
All data were submittedtothe data-coordinating centre within
the Clinical Trials Methodology Group,Henderson Research
Centre, Hamilton, ON,Canada. They were responsiblefor main-
taining the concealment of the random allocation sequence from
investigatorsand patients. The study design, analyses, and deci-
sion to publish were all determinedbythe investigators.
Study participants were scheduledtoattend fourvisits:
1) baseline;2)at8weeks (prior to cross-over); 3) at 12 weeks
(after the 4-week ‘wash-out’period); and 4) at 20 weeks.The Vil-
lalta Scale and VEINESquestionnaire were completed at all vi-
sits. TheGlobalRating Instrument wasadministeredatthe eight
and 20 week follow-up visits; thatis, at the end of each study
period.Study participants were alsoasked to keep adiary of the
number of hours theyusedthe device each day.
Participants were screened clinicallyfor recurrent venous
thromboembolism and the development of venous ulceration at
each visit. Adverse clinicalevents were adjudicated by ablinded
expertinThrombosis medicine.Seriousadverse eventswere re-
ported to Health Canada and the Research and Ethics Boards of
both centres.
Outcomes
The primaryoutcome was'clinical success' defined as fulfilling
all of the following criteria:1)the patient reported benefitfrom
the intervention; 2) experienced at least moderate improvement
in symptoms of PTS; and 3) waswilling to continue to use the de-
vice(Fig. 2). Secondary outcome measuresincludedeach of the
componentclinical successresponses,devicepreference, PTS
severity (Villalta Scale score), venous disease-specific quality of
Figure2:Globalratinginstrument. The
primaryoutcome was 'clinical success'defined
as fulfilling all of thefollowing criteria: 1) re-
ported benefitfromthe intervention; 2) at
least moderate improvement in symptoms of
PTS; and 3) willing to continuetouse the inter-
vention.

O'Donnell et al.Novel device to treatpost-thromboticsyndrome
626
life (VEINES-QOL) and severity of venous lowerlimb symp-
toms (VEINES-Sym).
Statisticalanalysis
Sample size wascalculated forthe primarybinary outcome
measure.From ourpreliminary pilot study (14),weestimateda
probability of clinicalsuccess with the active device of 67% in
subjects with severe PTS. Basedonpreviousresearch in this
field, we expectaplacebo effect of approximately 20%. We con-
sideredaminimum clinically important difference to be an addi-
tionalabsoluteprobability of clinical successof40%, that is a
probability of clinicalsuccess of 60% of clinicalsuccess with the
active device (Chi2=0.05, two-sided; power=80%). Taking into
account loss to follow-up (10%), we required atotal sample size
of 32 subjects.
The paired binaryoutcomes were analyzed primarily using
McNemar’stests, and secondly, using logistic mixed models to
account for correlation and period effects, and also to assess the
impact of potentiallyinfluential baseline covariates:gender,
body mass index(BMI), education,swelling, compression
stockings use.The paired continuous outcome measures(Villal-
ta and VEINESscalescores)were analyzed primarily using
paired t-tests, and secondly, using linear mixed models to ac-
count for correlation, baseline scores and aperiod effect,and an
extendedmodel adding the covariates listedabove.P-values less
than0.05 were considered to be statistically signif icant. All stat-
isticalanalyses were performed using SAS version 9.1(Cary,
NC,USA).
Results
Between February2004 and October 2005, 32 patients were re-
cruited.Thebaseline characteristics of participants are presented
in Table1.Mean age was50years,and 50% were women. Most
(80%) participants were using graduated compression stockings
at the time of recruitment. Twenty-six participants completed the
trial(Fig. 2). Threeparticipants withdrew during Period 1(one
patient died,two experienced side effects possibly related to the
device), twowithdrew during the wash-out period (one suffered
from depression, one withdrew to provide care to an ill spouse),
and onepatient withdrew during Period 2(experienced side ef-
fects possibly related to the device) (see Adverse Events)(Fig. 3)
Meanduration of use (perday)was 6.2hours (h) (SD 3.4) forVe -
nowave and 5.3h(SD 3.1) for control.
Clinical success
Aclinical successwas reportedin10participants usingtheVe no-
wave device, and in fourpatients usingthe control device;two of
these participants reported aclinical successwith both devices
(p=0.11).Inthe twopatients whoreported aclinical successwith
both devices,one had apreference for Ve nowave and oneapref-
erence for control. Fourteenparticipants (54%) didnot reporta
clinical successtoeitherdevice(Table2). Graduated compres-
sion stockings were worn by five of the eight participants whore-
ported aclinical successwith Ve nowave alone, and in allpartici-
pants whoreported eitheraclinical successwith the control de-
vicealone (n=2) or with both devices (n=2). Thelogistic model-
ing of clinical successproduced stronger treatment effects
(p=0.068 forthe multivariable modeladjusting for period effect
and baseline covariates), butshowednoevidenceofperiod or
baseline covariate main effects.
Secondaryoutcomes
Table2also presentsasummaryand analysis of the components
defining clinicalsuccess, and patient device preference.The
trend in favorofVe nowave wasconsistent across all threecom-
ponents; however, onlythe “benefit” component showedastrong
treatment effect.Therewas anon-significant benefitassociated
with Ve nowave forthe composite outcome of “benefit” from the
device and willing to “continue to use” the device,reported in
half of the participants using Ve nowave.Nineteen participants
preferred the Ve nowave while onlyfour preferred the control de-
vice; three preferred neither(P=0.003).
The VEINES questionnaire and Villalta scalewere com-
pleted fullyatall fourfollow-up assessments by 24 and 25 par-
ticipants respectively.Mean VEINES-QOL score at theend of
study period wassignificantly greater (P=0.004)for Ve nowave
(52.5; SD 5.8) compared to control (50.2;SD6.2). MeanVillal-
ta scalescoreatthe end of study period wassignificantly reduced
forVe nowave (12.2; SD 6.3) compared to control (15.0;SD6.1);
p=0.004 (seeTable 3).After adjustment for baseline scores, peri-
od effect and baseline covariates in the mixed model, alltreat-
ment effect analyses remained consistent with the results of the
pairedt-tests. There wasnoevidenceofa“carry-over” effect for
anyoutcome measure.
Table1:Baseline characteristics.
Characteristic
Number of patients 032
Age (years) – mean (range) 050 0(25–80)
Female gender – n(%) 016 0(50)
Weight (kg)–mean (range) 089 0(59–130)
Height (cm) – mean (range) 171(152–188)
Body mass index ≥25 – n(%) 025 0(78)
DVTdiagnosis (years)–mean (range) 005.2 00(0.7–17.7)
Pneumatic compression pumps–n(%) 00100(3)
Physical demandsoftypical day–n(%)
–Low 0080(25)
–Medium 013 0(41)
–High 010 0(31)
Avg. daytime hoursstanding – mean (range) 007.8 00(3–18)
Villalta Scale score – mean (range) 020 0(13–33)
Graduatedcompression stockings – n(%) 026 0(80)
Avg. daytime hourssitting – mean (range) 008.0 00(1–14)
Left leg withPTS – n(%) 026 0(81)

O'Donnell et al.Novel device to treatpost-thromboticsyndrome
627
Adverse events
One patient died during week 8(control deviceperiod). Thepa-
tient did not completePeriod 1and wasnot wearing the deviceat
the time of death. Causeofdeathwas deemed to be cardiacand
unrelated to the study.The patient did not have an autopsy,but
the case wasreviewedbythe localCoroner. Clinical details were
alsopresentedtothe localResearch and Ethics Boards and
HealthCanadaand determinedtobeunrelated to the study de-
vice.Nocases of recurrent venous thromboembolism were re-
ported. Oneparticipant withdrew from the trialbecauseofactive
venous ulceration that occurredafter aminor injurywhile wear-
ing the control device. He discontinuedwearing the deviceafter
the injury, and the small area of ulceration wasattributedtothe
injuryand wasdeemed to be unrelated to the studydevice. Three
other participants reported side-effects, deemed to be ‘non-seri-
ous’ and related or possibly related to the device. Allthreepar-
ticipants withdrew from the trial. Oneparticipant reported ‘leg
swelling, irritation and superficialbleeding’, onereported ‘skin
irritation’ and onereported ‘leg swelling with itching of skin’.
Figure3:Study flow.
Table2:Primaryoutcomeresults.
Patient-reported
outcome Venowave
TM
alone Control
alone Both
devices Neither
device P-value*
Clinical success†0822140.11
(1) Benefit reported with
device 12 36 050.035
(2) Moderate or greater
improvementinleg symp-
toms
0823130.11
(3) Willing to continue to
use device 11 53 070.21
Other outcomes
(4) Benefitand continue to
use§ 11 42 090.12
(5) Preferreddevice 19 40 030.003
†Requirementfor clinical success: outcomes (1) and (2) and (3). §Composite of outcomes (1) and (3). *McNemar’stest.

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Discussion
In this randomized controlledtrial of patients with severe PTS,
almost 40% of patients treated with Ve nowave reportedamean-
ingful clinical response. In addition, there wasastatistically sig-
nificant improvement in severity of PTS and venous disease-spe-
cific quality of life with Ve nowave treatment compared to con-
trol. Thechange in VEINES-QOLand VEINES-Sym scores
withVe nowave in our studyare similartothe clinicalchange ob-
servedinaprospectivecohortstudy of patients with sympto-
matic improvement after acuteDVT (between 1and 4months)
(17).
Although not statisticallysignificant forthe primarycom-
positeoutcome, we believe thatthese findings areofconsider-
able clinicalimportance. Severe PTSisresponsible for substan-
tialpersonal disability,work absenteeism,reduced quality of life
and increased health care costs (3–8). Themainstayofcurrent
therapy, graduated compression stockings, is often of limited
benefit in patients with severe PTS(11). In this study,most pa-
tients were using compression stockings at the time of recruit-
ment butcontinued to have severe symptoms despite their use.
Importantly,most patients whoreported abenefit withVe nowave
were alsousing graduated compression stockings concomi-
tantly. Therefore, Ve nowave can be used aloneorinconjunction
with graduated compression stockings. Compared with pneu-
matic compression pumps (12),Ve nowave allowedpatients to re-
main mobile,and the device improved, rather thaninterfered
with, activities of dailyactivitiesduring use.
Ve nowave appears to be safe. Themost common side-effects
attributedtoVe nowave were heat sensation, skin irritation and in-
creased sweating. No cases of recurrent venous thromboembol-
ism were reported during the studyperiod.However,sincethis
wasasmall study,and the duration of follow-up in this trial was
limitedtoeight weeks,further prospective studiesare required to
determine the long-termsafetyand tolerability of Ve nowave.
Although everyeffortwas made to maintain blindingof
study participants and research nurses,itislikelythat partici-
pants were aware of adifference between the activeand control
devices, giventhe mechanical natureofthe intervention. In addi-
tion to aplacebo effect,weexpected the control device to have an
activecomponent, namely added legcompression with planar
calf supportduring standing and walking.We, therefore, pres-
ented the control deviceasanalternative‘active’ device rather
thanplacebo.Four participants reported aclinical successwith
the control device, twoofwhich also had aclinical successwith
Ve nowave.Our choiceofcontrol device would be expected to in-
crease the likelihood of not finding atreatment effect when one
trulyexisted (i.e.type II error), undermining our ability to detect
astatistically significant benefitwith Ve nowave.
Themainlimitations of our studyare the small sample size
and shortduration of follow-up.Thatsaid, this studyisthe largest
clinicaltrial of treatment of severe PTS. Further studies are
required to determine the longer-termbenefits and safety of Ve -
nowave.Strengths of the studyare thatparticipants, investi-
gators, assessorsand data analyzers were all blindedand that
validatedscales were used to assess clinical outcomes.
In conclusion, Ve nowave appears to be averypromising new
therapyfor severe PTS, achronic disabling condition with li-
mited treatment options.Inour study population of patients with
severe PTS, refractory to standard therapies, almost40% of pa-
tients reported clinicalimprovement with Ve nowave.
Acknowledgement
We aregrateful to Gail McQueen forher effortsonthis study.
Table3:Secondaryoutcomeresults.
OutcomemeasureMean score (SD)
Baseline
n=26 Venowave
TM
n=26 Control
n§Difference
n§P-value*
VEINES Questionnaire
†
VEINES-Sym48.6 (5.3) 52.7 (6.9) 50.0 (7.2) +3.3(5.9) 0.01
VEINES-QOL 48.3 (4.4) 52.5 (5.8) 50.2 (6.2) +2.9(4.5) 0.004
Villalta Scale
‡
Symptoms component 10.1(2.7) 06.1 (3.2) 08.5 (3.9) –2.4 (2.9) 0.0003
Signs component 09.0 (2.3) 06.1 (4.3) 06.6 (3.5)–0.6 (3.6) 0.4
To talVillalta Score19.1 (3.4) 12.2 (6.3) 15.0 (6.1) –3.1 (4.9) 0.004
SD=standard deviation; QOL=qualityoflife. § n=26for Villalta symptoms, n=25 forVillaltasigns and total, n=24 forVEINES. *paired t-test fordifference between Venowave
TM
and control. †The Venous Insufficien-
cy Epidemiological and Economic Study (VEINES)questionnaireconsists of 26 items, 10 items measureseverity of symptoms, 9itemsmeasure limitations of dailyactivity,5itemsmeasure the psychological im-
pact of venous disease and 2itemscover time of daythat symptoms aremost severe and changeoverthe pastyear.Summary scoremay be computedin2ways; 1)VEINES-Quality of life(QOL), that includes
25 items and, 2)VEINES-symptoms that includes 10 items relating to severityofsymptoms.The itemmeasuring time of dayofmaximal symptoms is not included in either summarymeasure.Asthe number of
response categories varies betweenquestions,summary (mean) scores arecalculated by atransformation to z-scoreequivalents and then to at-scorewith mean=50and SD=10. Lowerscores indicate morese-
vere PTS. ‡The Villalta scale consists of 11 items, 5covering symptomsand 6covering lowerlimb signs (e.g. skin discoloration, swelling).Summary scores maybepresented as atotal score(maximum of 33
points) or divided into sub scores based on assessment of symptoms and signs of PTS.Higherscores indicate moreseverePTS.

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