Stakeholder Submissions
ECRI Institute invited NPWT device manufacturers and other interested
stakeholders (i.e., wound-related organizations) to submit relevant
clinical materials for consideration in the report (Table
14). Specifically, we requested the submission of published
or unpublished randomized controlled trials, observational studies
or other compelling evidence that uses NPWT to impact relevant
clinical outcomes. We were also interested in the submission
of materials regarding any ongoing clinical trials.
We identified the following relevant clinical materials from
the submissions that had not been identified in our searches:
one systematic review,(70)
two comparison studies,(71-72)
and 23 single arm studies(73-95)
for inclusion in this report. In addition, we included one unpublished
case series submitted by Smith and Nephew(96)
giving us a total of 24 additional case series included in this
report.
During the review process of the report, we received nine submissions
for possible inclusion in the report. Of these additional submissions,
we included one nonrandomized comparison study(106)
in this report. Counting this additional submission, three comparison
studies which were previously not identified by ECRI were included
in the report. For information on submissions by individual stakeholders,
please go to Appendix D.
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Previous Systematic Reviews
We identified a total of 22 systematic reviews, all published
between 2000 and 2008, that covered Negative Pressure Wound Therapy
(NPWT) devices. These reviews included studies reporting data
on NPWT for patients with a broad range of wound types. The reviews
also included information from studies assessing the comparative
effectiveness of NPWT with other wound treatments. A majority
of the studies included what were regarded as traditional comparators
or "standard of care." In addition, all of the reviews
included additional interventions such as gel systems, bolster
dressings, hydrocolloid gels, and other topical treatments. All
of the studies reported using the V.A.C.® system (KCI). None
of the reviews included studies that compared one NPWT system
to another. For more information about the conclusions drawn
from these reviews, go to Table 11.
The two earliest reviews (published in 2003) will not be discussed
here.(168-169) The evidence
base for ten of the 20 reviews published since 2004 focused strictly
on comparison studies. The remaining reviews also included retrospective
studies, case studies, and cost-effectiveness analyses, with
one review included animal studies.(170)
Further information about the reviews and individual studies
included can be found in Table
39 and Table 40 in Appendix
C, respectively.
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Quality of the Systematic
Reviews
We assessed the quality of each review using the Assessment
of Multiple Systematic Reviews (AMSTAR) measurement tool.(171)
AMSTAR consists of 11 items used to assess whether or not a systematic
review includes important elements, such as a comprehensive literature
search, assessment of study quality, appropriate methods to combine
study findings and assessment of publication bias. To rate the
quality of the review, we have applied a rating of "High" if
the review received at least 8 "yes" responses, and
a rating of "Low" if the review received 8 or more "no" responses.
Studies with mixed responses between these ranges were assigned
a rating of "Moderate." Based on these criteria, we
found that 12 of the 20 included reviews were of moderate quality.
The remaining reviews were graded as high (3) or low (5). All
of the high-quality reviews performed duplicate study selection,
assessed the likelihood of publication bias, and indicated conflict
of interest; three items typically omitted by other reviews.
None of the low-quality reviews assessed the quality of included
studies and only half performed a comprehensive literature search.
Complete details of our quality assessment can be found in Table
41.
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Findings of the Systematic
Reviews
High Quality Reviews
None of the high-quality reviews concluded that NPWT provided
additional benefit when compared to other interventional treatments.(172-174)
The first high-quality review focused solely on treatment of
burn wounds, and included only one small trial.(172)
Twenty patients (serving as their own controls) were randomized
to either a 48-hour treatment of topical negative pressure (TNP),
a term used by the authors for NPWT, or silver sulphadiazine
(SSD). Significant differences in favor of NPWT were reported
at day 3 and day 5, however, no difference was reported at day
14. Shortcomings reported by study authors included absence of
reporting clinically relevant outcomes and a limited description
of randomization methods and allocation concealment.
The second high-quality review, included 17 comparison studies
(ten RCTs) evaluating various wound types and reported a benefit
to patients treated with NPWT for surrogate outcomes of wound
healing.(173) Significant
advantages in favor of NPWT were reported in four of seven studies
reporting wound closure as well as a significantly faster rate
of wound healing reported in one large RCT. Despite these favorable
results, the authors concluded that the overall evidence was
insufficient to clearly prove an additional clinical benefit
of NPWT.
The remaining high-quality review included seven RCTs and concluded
no significant benefit was shown in the treatment of chronic
wounds with NPWT when compared to moistened gauze dressings or
other topical agents. Small study populations, unclear allocation
methods, and lack of blinding of outcome assessors were all indicated
as methodological flaws in the NPWT literature.(174)
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Moderate Quality Reviews
Five of twelve (42%) moderate-quality reviews concluded that
NPWT was more effective than the control treatments.(175-178)
One of these reviews focused only on patients with post-sternotomy
mediastinitis (PM).(175)
Two nonrandomized comparison studies included in this review
evaluated overall survival and quality of life (QOL) as primary
outcomes. The Health Survey Questionnaire given to patients in
one study resulted in a significant difference in the QOL in
favor of V.A.C.® therapy over sternum removal.(130)
One study of 102 patients demonstrated overall survival in the
V.A.C.® group as significantly higher than in the conventional
treatment; 97% versus 84% (6 months), 93% versus 82% (one year)
and 83% versus 59% (five years).(139)
A larger retrospective study by the same authors(179)
comparing 46 PM coronary artery bypass patients treated with
V.A.C.® therapy to 4,781 coronary artery bypass patients
without mediastinitis. Results from this trial, however, demonstrated
V.A.C.® treated patients faring as well as the non-infected
cohort with no significant differences found in early or late
survival between the groups. Lastly, one review evaluated use
of NPWT in the management of diabetic foot ulcers. Results from
four RCTs indicated that NPWT was more effective than comparator
treatments. The quality of the evidence was weak however and
patient selection was limited to patients with sufficient blood
supply which "distorts the perceived clinical benefits
of the therapy."(70)
Two reviews concurred that NPWT appeared to be more effective
than topical treatments in the management of skin grafts and
soft tissue flaps.(176-177)
Three studies,(124, 131-132)
covered in both reviews, reported that use of NPWT resulted in
fewer tissue flaps per patient,(124,132)
and improved reepithelialization.(132)
Another review described the evidence as "tentative" for
NPWT being as good as other therapies for some wounds. The authors
reviewed a variety of studies of NPWT used for pressure ulcers,
post-traumatic wounds, diabetic foot ulcers, venous and arterial
leg ulcers, and mixed wound types and included 14 RCTs in their
evaluation. Although NPWT appeared to be at least as effective
as other wound treatments, the interpretation was "hampered
by the diversity of the study designs and the methodological
weaknesses in the studies."(178)
The remaining seven reviews reported either a comparable benefit
or no benefit in comparison to control treatments.(25, 107, 180-184)
A comparable benefit was seen for acute lower limb trauma and
burn wounds in one review.(25)
Positive outcomes for 34 patients with fasciotomy after tibial
compartment syndrome included a statistically significant shorter
time to closure compared to standard dressing. Patients with
burn wounds benefited by NPWT treatment with less graft loss
and shorter hospital stay. Based on evidence from six comparison
and several case series, the authors concluded that the effectiveness
of NPWT was comparable to the standard dressing and wound coverage
methods.
Mixed results were obtained by one reviewer focusing on treatment
of pressure ulcer wounds with the Healthpoint System of topical
wound treatments.(107) Two
of five RCTs, only including patients with pressure ulcers, found
no significant differences in wound healing. The remaining three
studies, examining wounds with mixed etiologies, found a decrease
of wound treatment time in favor of V.A.C.®. Study authors,
however, caution the interpretation of these findings due to
the lack of a subgroup analysis which is an essential component
to studying effects of different interventions in patients with
wounds of mixed etiology.
No benefit to treatment was seen by the remaining moderate-quality
reviews. The largest review, published in 2007, assessed over
700 patients treated with six treatment methods. Based on the "newly
available evidence" authors indicated that no clear statement
about the clinical efficacy and safety of NPWT could be made.(180)
Two reviews evaluated treatments for various wound types. One
concluded no worthwhile evidence supported the use of NPWT,(183)
while the other stated that the more credible evidence suggested
no benefit from V.A.C.® therapy when compared to standard
of care and OpSite dressings.(181)
A review of six RCTs based their recommendation on one highly
rated RCT due to the poor quality ratings of the five other studies.(184)
Patients with acute, surgical wounds from partial foot amputations
were randomized to NPWT or standard care. In addition, some underwent
surgical closure. The authors concluded that no statistically
significant difference existed between NPWT and standard care
in the rate of complete wound closure (patients had complete
wound closure but did not undergo surgical wound closure).
Six RCTs qualified for inclusion in the final review; five of
the included studies examined fewer than 25 patients.(182)
No significant advantage was seen for NPWT on primary endpoints
(i.e., complete healing) while varying results were found for
secondary endpoints (i.e., QOL).
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Table 11. Summary of
Conclusions
| Reference |
Title |
Author's Conclusions |
Study Quality Rating |
| Gregor et al. 2008 (173) |
Negative Pressure Wound Therapy: A Vacuum of Evidence? |
Overall evidence was insufficient to clearly prove an additional
clinical benefit of NPWT. |
High-Quality Review |
| Ubbink et al. 2008 (174) |
Topical negative pressure for treating chronic wounds |
No significant benefit was shown in the treatment of chronic
wounds with NPWT when compared to moistened-gauze dressings
or other topical agents. |
High-Quality Review |
| Wasiak and Cleland 2007 (172) |
Topical negative pressure (TNP) for partial thickness
burns |
There is a paucity of high-quality RCTs on for partial-thickness
burn injury, with insufficient sample size and adequate power
to detect differences, if there are any, between NPWT and
conventional burn wound therapy dressings. |
High-Quality Review |
| Noble-Bell et Forbes 2008 (70) |
A systematic review of the effectiveness of negative
pressure wound therapy in the management of diabetes foot
ulcers |
Although evidence from four RCTs indicated that NPWT is
more effective than comparator treatments, study quality
was weak to moderate. |
Moderate-Quality Review |
| Schimmer et al. 2008 (175) |
Management of post-sternotomy mediastinitis: experience
and results of different therapy modalities |
Based on retrospective studies alone (no prospective randomized
trials have been published), benefits to treatment of post-sternotomy
mediastinitis with VAC included less treatment failure, shorter
postoperative stay, lower rates of recurring infection, improved
QOL, and an increase in overall survival. Prospective randomized
controlled trials are needed. |
Moderate-Quality Review |
| Ubbink et al. 2008 (183) |
A systematic review of topical negative pressure therapy
for acute and chronic wounds |
There is no worthwhile evidence to support the use of NPWT
in the treatment of various wounds. |
Moderate-Quality Review |
| van den Boogaard et al. 2008 (107) |
The effectiveness of topical negative pressure in the
treatment of pressure ulcers: a literature review |
Topical negative pressure wound therapy has not proven
to be more effective than various control interventions. |
Moderate-Quality Review |
| Vikatmaa et al. 2008 (178) |
Negative Pressure Wound Therapy: a Systematic Review
on Effectiveness and Safety |
NPWT appears to be a safe alternative treatment. There
is tentative evidence that NPWT is at least as good as or
better than current local treatment for wounds. However,
there is a shortage of reliable research data on the effectiveness
of NPWT. |
Moderate-Quality Review |
| Costa et al. 2005 (modified 2007) (181) |
Vacuum-assisted wound closure therapy (V.A.C.®) |
There is insufficient evidence to recommend the routine
use of VAC therapy. |
Moderate-Quality Review |
| Kanakaris et al. 2007 (25) |
The efficacy of negative pressure wound therapy in
the management of lower extremity trauma: Review of clinical
evidence |
Based on evidence from a limited number of controlled trials,
authors recommend the use of NPWT in the acute phase of blunt,
penetrating and thermal trauma of the extremities. |
Moderate-Quality Review |
| Vlayen et al. 2007 (180) |
Vacuumgeassisteer de Wondbehandleing: e en Rapid Assessment |
The newly available evidence did not allow the authors
to make a clear statement about the clinical efficacy and
safety of NPWT. |
Moderate-Quality Review |
| Ontario Health Technology Advisory Committee
2006 (184) |
Negative Pressure Wound Therapy: Update |
Based on the evidence to date, the clinical effectiveness
of NPWT to heal wounds is unclear. |
Moderate-Quality Review |
| Pham et al. 2006 (176) |
The safety and efficacy of topical negative pressure
in non-healing wounds: a systematic review |
There is a paucity of high-quality RCTs of topical negative
pressure for wound management with sufficient sample size
and adequate power to detect any differences between topical
negative pressure and standard dressings. |
Moderate-Quality Review |
| Gray & Pierce 2004 (177) |
Is Negative Pressure Wound Therapy Effective for the
Management of Chronic Wounds? |
Based on two small studies, NPWT may be superior to saline-moistened
gauze in the treatment of chronic wounds. Insufficient evidence
exists to determine whether NPWT is superior to advanced
dressings in promoting healing of pressure ulcers and diabetic
foot ulcers. In addition, based on three quasi-experimental
studies, superiority of NPWT was determined in the treatment
of soft-tissue flaps and skin grafts when compared to topical
antimicrobial agents and gauze. |
Moderate-Quality Review |
| Samson et al. 2004 (182) |
Wound-Healing Technologies: Low-level Laser and Vacuum-assisted
Closure |
VAC trials did not find a significant advantage for intervention
on primary endpoint, complete healing, and did not consistently
find significant differences on secondary endpoints. Evidence
was limited by poor study quality. |
Moderate-Quality Review |
| Contractor et al. 2008 (185) |
Negative Pressure Wound Therapy With Reticulated Open
Cell Foam in Children: An Overview |
The evaluation of single case studies and retrospective
reviews revealed V.A.C.® as a safe alternative to traditional
methods in treating axial, chronic extremity wounds and complex
lawnmower injuries. Additional benefits included a reduction
in infection rates in tibial shaft fractures and spinal fusions.
Randomized prospective studies are needed to make recommendations
for the safe and efficacious clinical practice. |
Low-Quality Review |
| Schintler and Prandl 2008 (170) |
Vacuum-assisted closure—what is evidence based? |
The investigators concluded that vacuum therapy, when used
by experienced surgeons, is an excellent option to support
wound healing. Although this therapy appears effective, its
superiority to conventional techniques has not been demonstrated.
Further prospective randomized blinded studies are needed. |
Low-Quality Review |
| Raja and Berg 2007 (186) |
Should vacuum-assisted closure therapy be routinely
used for management of deep sternal wound infection after
cardiac surgery? |
Current evidence is weak to support the routine use of
V.A.C.® for management of deep sternal wound infection
after cardiac surgery. |
Low-Quality Review |
| Mendonca et al. 2006 (187) |
Negative-pressure wound therapy: a snapshot of the
evidence |
Due to the mixed results in the few RCTs examined, the
authors cannot confirm a clear clinical effectiveness of
TNP. |
Low-Quality Review |
| Gupta and Cho 2004 (188) |
A Literature Review of Negative Pressure Wound Therapy |
Based on 61 retrospective studies and 3 prospective studies,
the authors conclude that the clinical outcomes demonstrate
significance in all of the comparative Study with overall
outcome data supporting its effectiveness. |
Low-Quality Review |
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Meta-Analysis
In only one of the reviews did the authors perform a meta-analysis
using wound-healing data from patients treated with NPWT.(173)
In this review, an analysis of four RCTs and two nonrandomized
controlled trials (non-RCTs) for change in wound size indicated
results favoring NPWT (standardized mean difference (SMD): RCTs,
-0.57; 95% CI, -0.94 to -0.20; non-RCTs: SMD, -1.30; 95% CI,
-2.07 to -0.54). Reasons given in the Cochrane review by Ubbink
et al. for not performing meta-analysis included the diverse
endpoints and comparator treatments in the trials.(174)
Furthermore, these authors criticize the use of data from subgroup
analyses and of the incorporation of non-quantitative comments
(e.g., "some patients experienced pain") in other reviews
of NPWT.
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Adverse Events
Finally, the authors were in overall agreement that NPWT is
a safe alternative treatment. Reported complications included
infection, hematoma, fistulas, failure to heal, osteomyelitis
and pain. Although serious harms from treatment with NPWT including
mortality and re-amputation have been reported, they are rare.
For a complete listing of reported adverse events related to
NPWT and comparator treatments, please go to Table
42.
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Overview of the Systematic
Reviews
The systematic reviews of NPWT reveal several important points
about this technology. First, all of the systematic reviews noted
the lack of high-quality clinical evidence supporting the advantages
of NPWT compared to other wound treatments. The lack of high-quality
NPWT evidence resulted in many systematic reviewers relying on
low-quality retrospective studies to judge the efficacy of this
technology. Second, the other systematic reviews found no studies
directly comparing different NPWT products have been published.
Direct comparison studies are especially important in determining
which dressing approach (foam or gauze) may provide the best
potential for wound healing. Third, other systematic reviews
concluded that NPWT must be evaluated according to wound type.
Wound healing varies according to the type of wound being treated
and NPWT benefits described for one wound type cannot be transferred
to other wound types. Most wound types have too little high-quality
NPWT evidence to judge if NPWT is better than standard care for
specific wounds. Studies comparing foam to gauze are needed for
each wound type before decisions can be made about which systems
or components offer significant therapeutic distinctions.
Peinemann et al.(189) have
examined the potential for publications bias within the NPWT
clinical literature. Publications bias is the tendency to publish
only positive results and not to publish results that suggest
no difference in measured outcomes. If publication bias were
to exist within the NPWT literature, any conclusions based on
this literature would be inaccurate. The authors completed literature
searches for RCTs comparing NPWT with other wound therapies and
examined congress proceedings and online trial registers for
clues to unpublished RCTs. Manufacturers of NPWT devices (Kinetic
Concepts Inc. and BlueSky Medical Group Inc.) and authors of
conference abstracts were contacted and asked to provide study
information. Responses were received from 10 of 17 (59%) authors
and both manufacturers. Trials were considered nonrandomized
if concealment of allocation to treatment groups was classified
as "inadequate." An RCT was classified as "unpublished" if
no full-text paper on final study results (completed trials)
or interim results (discontinued trials) was available. A total
of 28 RCTs referring to at least 2755 planned or analyzed patients
met the inclusion criteria. Thirteen RCTs had been completed,
six had been discontinued, six were ongoing, and three RCTs had
an unclear status. Full test papers were available on only 30%
of the patients from 19 completed or discontinued RCTs. Of the
14 conference abstracts that reported on findings from these
19 RCTs, six abstracts were later published as full-text articles.
Peienemann et al. speculated that "some of these RCTs remained
unpublished because they were of poor quality or produced negative
results," concluded that the "lack of access to unpublished
study results data raises doubts about the completeness of the
evidence base on NPWT."(189)
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