Stakeholder Submissions

Technology assessment on negative pressure wound therapy devices.

 

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 Specifically, we requested the submission of published or unpublished randomized controlled trials, observational studies or other compelling evidence that uses NPWT to impact relevant clinical outcomes.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 In addition, we included one unpublished case series submitted by Smith and Nephew(96) giving us a total of 24 additional case series included in this report.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

ReferenceTitleAuthor's ConclusionsStudy 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 woundsNo 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 burnsThere 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 ulcersAlthough 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 modalitiesBased 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 woundsThere 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 reviewTopical 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 SafetyNPWT 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 evidenceBased 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 AssessmentThe 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: UpdateBased 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 reviewThere 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 ClosureVAC 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 OverviewThe 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 evidenceDue 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 TherapyBased 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)

Current as of November 2009
Internet Citation: Stakeholder Submissions. November 2009. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/research/findings/ta/negative-pressure-wound-therapy/stakeholder-submissions.html