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Negative pressure wound therapy for treating foot wounds in people with diabetes mellitus

  1. Jo C Dumville1,*,
  2. Robert J Hinchliffe2,
  3. Nicky Cullum3,
  4. Fran Game4,
  5. Nikki Stubbs5,
  6. Michael Sweeting6,
  7. Frank Peinemann7

Editorial Group: Cochrane Wounds Group

Published Online: 17 OCT 2013

Assessed as up-to-date: 30 JUL 2013

DOI: 10.1002/14651858.CD010318.pub2


How to Cite

Dumville JC, Hinchliffe RJ, Cullum N, Game F, Stubbs N, Sweeting M, Peinemann F. Negative pressure wound therapy for treating foot wounds in people with diabetes mellitus. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD010318. DOI: 10.1002/14651858.CD010318.pub2.

Author Information

  1. 1

    University of Manchester, Department of Nursing, Midwifery and Social Work, Manchester, UK

  2. 2

    St George's Healthcare NHS Trust, St George's Vascular Institute, London, UK

  3. 3

    University of Manchester, School of Nursing, Midwifery and Social Work, Manchester, UK

  4. 4

    Derby Hospitals NHS Foundation Trust, Department of Diabetes and Endocrinology, Derby, UK

  5. 5

    Leeds Community Healthcare NHS Trust, St Mary's Hospital, Wound Prevention and Management Service, Leeds, UK

  6. 6

    Institute of Public Health, MRC Biostatistics Unit, Cambridge, UK

  7. 7

    Children's Hospital, University of Cologne, Cologne, NW, Germany

*Jo C Dumville, Department of Nursing, Midwifery and Social Work, University of Manchester, Manchester, M13 9PL, UK. jo.dumville@manchester.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 17 OCT 2013

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Characteristics of included studies [ordered by study ID]
Armstrong 2005

Methods2-arm RCT; undertaken in USA (in wound and academic centres)


Participants162 adult participants

Inclusion criteria: presence of: (1) wound from a diabetic foot amputation to the transmetatarsal level of the foot; (2) adequate perfusion; (3) University of Texas grade 2 or 3

Exclusion criteria: people presenting with (1) active Charcot arthropathy of the foot; (2) wounds resulting from burns; (3) venous insufficiency; (4) untreated cellulitis or osteomyelitis (after amputation); (5) collagen vascular disease; (6) malignant disease in the wound; or people treated with: (7) corticosteroids;  (8) immunosuppressive drugs or chemotherapy; (9) NPWT (in the last 30 days); (10) growth factors; (11) normothermic therapy; (12) hyperbaric medicine; (13) bioengineered tissue products (in the last 30 days)

Key baselines co-variates:

Wound area (cm2):

Group A: 19.2 (SD = 17.6)

Group B: 22.3 (SD = 23.4)

 

Wound duration (months):

Group A: 1.8 (SD = 5.9)

Group B: 1.2 (SD = 3.9)

75.3% of the study population had wounds that were < 30 days' duration (classed as acute wounds by the author) and 24.7% had wounds that were > 30 days' duration (classed as chronic wounds by authors)


InterventionsGroup A (n = 85): moist wound therapy with alginates, hydrocolloid, foam or hydrogel dressings – adhering to standardised guidelines at the discretion of attending clinician. Dressings changed every other day unless recommended by treating clinician

Group B (n = 77): NPWT (VAC® system) no information provided regarding the pressure applied or the cycle (e.g. constant/cyclical etc); dressing changes every 48 h. Treatment conducted until wound closure or completion of 112 day assessment.

 

All participants received: (1) off-loading therapy, preventatively and therapeutically as indicated - a pressure relief sandal or walker was provided for all participants; (2) sharp debridement within 2 days of randomisation and as deemed necessary by treating clinician; and, (3) measurement of pre-albumin, albumin and HbA1c levels in 7 days before entering the study. Low pre-study albumin levels resulted in consultation with nutritionist, and dietary supplement initiated if needed. 


OutcomesPrimary outcome: (1) number of wounds completely healed (defined as 100% re-epithelialisation without drainage and INCLUDED closure via surgery where the decision for surgical closure was made by treating clinician); (2) time to wound healing; (3) amputation

Secondary outcomes: (1) other adverse events (serious and non-serious); (2) resource use


NotesFollow-up: 112 days (16 weeks)

Outcome assessment: based on data from wound assessments and digital photographs taken by treatment clinicians at days 0, 7, 14, 28, 42, 56, 84 and 112

A secondary analysis of trial data reported that 75% of wounds were ≤ 1 month in duration (classed by authors as acute) and 25% were > 1 month in duration (classed by authors as chronic). We note that mean baseline values for ulcer duration were obviously very skewed

Funding: study funded by KCI – manufacturers of the VAC® intervention


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomisation was accomplished by using www.randomizer.org to generate 15 blocks of 10  random numbers each."

Comment: adequate methodology

Allocation concealment (selection bias)Low riskQuote: "Numbers were systematically assigned to each treatment group, and sealed envelopes containing opaque, black paper labelled with assigned treatment and patient ID number were sequentially numbered and provided to each site. The black paper was added to ensure that the contents of the envelopes were not visible prior to opening."

Comment: adequate methodology

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: it is understandably not possible to blind participants and patients to whether or not they receive NPWT. However, given this, it is important that any decision-making that might be affected by performance bias is recognised and blinding is introduced where possible.  We note that unblinded health professionals were able to make decisions about closure surgery that could then have resulted in more wounds being closed (and classed as healed) or amputated in one group compared to the other. As a result of this we classed the risk of bias for this domain as unclear.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "Neither patients nor investigators were masked to the randomised treatment assignment . . . However, notes that the masking component of the study dealt specifically with planimetry measurements from digital photographs . . . concordance between the investigator and the digital planimetry provided independent confirmation of the primary efficacy endpoint of complete wound healing."

Comment: assessment of healing seems to have had a blinded component

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: no evidence of incomplete outcome data

Other biasLow riskNo evidence of other bias

Blume 2008

Methods2-arm RCT; undertaken in USA


Participants342 adult participants

Inclusion criteria: (1) stage 2 or 3 (Wagner’s scale) calcaneal, dorsal or planter foot ulcer; ulcer ≥ 2 cm2 in area after debridement; (3) adequate blood perfusion (various tests and cut-offs reported)

Exclusion criteria: (1) recognised active Charcot disease; (2) ulcers resulting from electrical, chemical or radiation burns; (3) collagen vascular disease; (4) ulcer malignancy; (5) untreated osteomyelitis or cellulitis; (6) uncontrolled hyperglycaemia; (7) inadequate lower extremity perfusion; (8) pregnant or nursing mothers; or ulcer treatment within 30 days of trial start with (9) normothermic or hyperbaric oxygen therapy, (10) corticosteroids, (11) immunosuppressive drugs, (12) chemotherapy, (13) recombinant or autologous growth factor products, (14) skin and dermal substitutes; or (15) use of any enzymic debridement treatment.

Key baselines co-variates:

Wound area (cm2):

Group A: 11.0 (SD = 12.7)

Group B: 13.5 (SD = 18.2)

 

Wound duration (months)

Group A: 6.9  (SD = 12.2)

Group B: 6.6 (SD = 10.8)


InterventionsGroup A (n = 169): advanced moist wound therapy dressings used according to guidelines/local protocols - noted as being predominantly hydrogels and alginates

Group B (n = 172): NPWT (VAC® system) applied according to manufacturer’s instructions, but no information provided about the pressure applied or the cycle (e.g. constant/cyclical etc).  Treatment continued until wound closure, or until there was sufficient granulation tissue formation for healing by primary and secondary intention

All participants received: (1) assessment and debridement of ulcers within 2 days of randomisation; (2) off-loading therapy as deemed necessary


OutcomesPrimary outcome: (1) number of wounds completely healed (defined as 100% re-epithelialisation without drainage or dressing requirement and INCLUDED closure via surgery where the decision for surgical closure was made by treating clinician); (2) time to wound healing; (3) amputation

Secondary outcomes: (1) other adverse events (serious and non-serious); (2) resource use


NotesFollow-up: 112 days (16 weeks)

Outcome assessment: participants examined weekly for the first 4 weeks and then every other day until day 112, or ulcer closure by any means. Participants achieving closure were followed up at 3 and 9 months

Funding: study funded by KCI – manufacturers of the VAC® intervention


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote:"Randomization was accomplished by generating blocks of numbers through http://www.randomizer.org."

Comment: adequate methodology

Allocation concealment (selection bias)Low riskQuote: "Numbers were assigned to a treatment group and sealed in opaque envelopes containing black paper labelled with treatment and patient ID. Envelopes were sequentially numbered before clinical trial site distribution. At patient randomisation, treatment was assigned on the basis of the next sequentially labelled envelope."

Comment: adequate methodology

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: It is understandably not possible to blind participants and patients to whether or not they receive NPWT. However, given this, it is important that any decision-making that might be affected by performance bias is recognised and blinding is introduced where possible.  We note that unblinded health professionals were able to make decisions about undertaking closure surgery that could then have resulted more wounds being closed (and classed as healed) or amputated in one group compared with the other. As a result of this we classed the risk of bias for this domain as unclear

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "Blinded photographic evaluation was conducted."

Comment. whilst the main report has no discussion of blinded outcome assessment, it is mentioned in the conference abstract describing the study. However as with Armstrong 2005 we note that unblinded health professionals in 1 group were able to make decisions about undertaking closure surgery that could then have resulted more wounds being closed (and classed as healed) or amputated. As a result of this we classed the risk of bias for this domain as unclear

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: 3 participants were excluded from analysis in each arm as they did not receive the trial treatment allocated. There were relatively low numbers of exclusions, although ideally data on these participants would have been included in the RCT report. Additionally, 31% of participants in the NPWT group and 25% in the dressing group were classed as being 'discontinued' for reasons that included adverse events, ineffective treatment and also death. It is not clear whether participants who were discontinued for reasons other than death were also censored from the analysis, rather than being followed up. If discontinuation did result in censoring in this open trial it may have introduced bias

Other biasLow riskNo evidence of other bias

Karatepe 2011

Methods2-arm RCT; undertaken in Turkey


Participants67 adult participants.

Inclusion criteria: diabetic foot ulcers

Exclusion criteria: not reported

Key baselines co-variates:

Wound area (cm2):

Group A: 29.7 (SD 5.2)

Group B: 35.7 (SD 6.4)

 

Wound duration (weeks):

Group A: 8.8 (SD 7.2)

Group B: 11.3 (9.2)


InterventionsGroup A (n = 37): conventional wound care treatment (described as daily wound care, debridement and treatment of gangrenous tissue where required and use of sterilized gauze dressing).

Group B (n = 30): NPWT  (VAC® system)

Clinical measures included standard diabetic treatment, daily wound care including antiseptic bath, debridement, toe removal for gangrene when necessary, and wound care with conventional methods or VAC®. 


OutcomesPrimary outcome: time-to-healing

Secondary outcomes: health-related quality of life measured with  SF-36 (not clearly reported)


NotesFollow-up: final SF-36 form completed 1 month after wound healing (mean in 4th month of study)

Outcome assessment: healing time calculated as the time from hospital admission to re-epithelization

Funding: not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomisation of the patients was arranged by the free use web based system (http://www.tufts.edu\˜gdall/PLAN.HTM)"

Comment: classed as an adequate method

Allocation concealment (selection bias)Unclear riskNot reported

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported

Other biasLow riskNo evidence of other risk of bias

Mody 2008

Methods2-arm RCT; undertaken in India


Participants48 participants (recruited from inpatient wards), 15 of whom were reported to have DM and a foot ulcer. Data for these 15 participants only are presented

Inclusion criteria: people admitted to general surgery, physical medicine, and rehabilitation wards and referred by the surgical consultants for care of an acute or chronic extremity, sacral, or abdominal wound that could not be treated with primary closure

Exlusion criteria: (1) ischaemic wounds; or wounds: (2) in anatomical locations where an adequate seal around the wound site could not be obtained; (3) with exposed bowel or blood vessels; (4) with necrotic tissue that could not be debrided; (5) with communicating fistulae; (6) with malignancy; (7) with recent grafts; or (8) presence of osteomyelitis; or (9) patient receiving therapeutic anticoagulation

Key baselines co-variates (foot ulcers in people with diabetes only):

Wound area (cm2):

Group A: 48.1 (SD = 53.5)

Group B: 25.7 (SD = 9.7)

 

Wound duration (days):

Group A: 5.2 (SD = 2.3)

Group B: 8.5 (SD = 8.3)


InterventionsGroup A (n = 9): saline-soaked gauze and dry pads used to cover the wound. Dressing changes typically performed twice daily; frequency adjusted according to the judgment of the treating physician

Group B (n = 6): locally-constructed (homemade) device: a sterilized, porous packing material obtained from a local source was cut to fit the wound. A 14-French suction catheter was tunnelled into the packing material, which then was placed into the wound cavity. A sterile adhesive plastic drape (Dermincise, Vygon, UK) was cut to overlap the surrounding skin and applied over the packing material, forming an airtight seal. Tubing was used to attach the free end of the suction catheter to a wall suction canister. The TNP timer was placed in circuit between the wall suction apparatus and the wall suction canister

The TNP timer, constructed from local electronics, was designed to cycle wall suction intermittently using a simple timed switch and a system of valves. For the study protocol, the timer was set to cycle for 2 minutes on, followed by 5 minutes off. Wall suction pressure was set at 125 mmHg. In sensitive wounds, suction was reduced to a tolerable level (usually 50 mmHg to 100 mmHg) until it could be comfortably increased. For oedematous wounds, the suction was kept on a continuous setting until oedema had been reduced and an intermittent regimen could be followed. The dressing was changed every 2 days unless otherwise scheduled by the treating physician. Wounds were debrided as required to keep the wound bed free of necrotic tissue. Patients receiving NPWT who no longer required hospitalisations for their primary diagnosis, or could not afford to remain in the hospital, remained in the study with conventional wound dressings in the outpatient setting, but outcomes were analysed in the original treatment groups

Wounds in both treatment groups were debrided before dressing application


OutcomesPrimary outcome: number of days to satisfactory healing, defined as complete wound closure by secondary intention or wound readiness for delayed primary closure as determined by the study investigator and treating surgeon

Secondary outcomes: none reported separately for foot ulcers


NotesParticipants were followed until wound closure or being lost to follow-up for an average of 26.3 days (+/- 18.5) in the control and 33.1 days (+/- 37.3) in the treatment group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Wounds that met inclusion and exclusion criteria were assessed for size (in a manner that allowed blinding) and then block-randomized using a concealed computer-generated table in a 1-to-2 ratio of TNP closure versus conventional wound dressing."

Comment: adequate method

Allocation concealment (selection bias)Unclear riskQuote: "Following enrolment, wound size was assessed using computer-aided measurements of digital photographs and block-randomized to the study arms using a concealed allocation table."

Comment: unclear how allocation concealment was conducted

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskSeems that participants were analysed in groups as randomised

Other biasUnclear riskNo evidence of other risk of bias

Novinščak 2010

Methods3-arm RCT; undertaken in Croatia


Participants27 adult participants

Inclusion criteria: complicated diabetic ulcer (sic) managed to international guidelines for treatment protocol (confirmed with the author that these were all foot wounds)
Exclusion criteria: revascularization, reconstruction and amputation procedures were not considered in this study

Key baselines co-variates: not reported

Wound duration (months): not reported


InterventionsGroup A (n = 8): classic gauze

Group B (n = 12): moist dressings
Group C (n = 7): NPWT

Surgical debridement, off-loading, co-morbidity treatment and appropriate wound care were performed


OutcomesPrimary outcome: healing rate (author defined as wound closure – personal contact)


NotesFollow-up: 2 months, extracted from abstract only


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot reported

Allocation concealment (selection bias)Unclear riskNot reported

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported

Other biasUnclear riskNo evidence of other risk of bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Armstrong 2012Included multiple wounds types. Unable to obtain diabetic foot wound data separately

Braakenburg 2005Included multiple wounds types. Unable to obtain diabetic foot wound data separately

ChongNo relevant outcome reported

Eginton 2003No relevant outcome reported

Etoz 2007Not an RCT, as participants allocated using alternation

Foo 2004No relevant outcome reported

Maggio 2010Treatment with NPWT was not the only systematic difference between groups (intervention group receiving NPWT also received autologous fibroblasts and skin grafting)

McCallon 2000Not an RCT, as participants allocated using alternation. Coin flipped for first participant and then participants allocated by alternation

Moues 2004Not a diabetic foot wound study population

Perez 2010Included multiple wounds types. Unable to obtain diabetic foot wound data separately

Rahmanian-Schwarz 2012Included multiple wounds types. Unable to obtain diabetic foot wound data separately

Riaz 2010Included wounds in people with diabetes in regions other than the foot (legs and back). Unable to obtain diabetic foot wound data separately

Sepulveda 2009No relevant outcome reported

 
Characteristics of studies awaiting assessment [ordered by study ID]
Sun 2007

MethodsNot clear: could be an RCT

ParticipantsPeople with DM and foot ulcers n = 38

InterventionsNPWT

OutcomesNot clear - seems to be wound dimensions

NotesRequires translation from Chinese

Tuncel 2013

MethodsRCT

ParticipantsMixed - request data for foot wound participants and further details

InterventionsNPWT

OutcomesRequested wound healing data from authors

Notes

 
Characteristics of ongoing studies [ordered by study ID]
ISRCTN34166832

Trial name or titleRCT PICO pilot study (Smith and Nephew)

MethodsRCT

ParticipantsChronic and sub-acute wounds (some potentially foot wounds in people with DM). Planned sample size of 100

InterventionsNPWT vs standard care

OutcomesTime to wound closure

Starting date

Contact informationEmma.Whatley@smith-nephew.com

NotesISRCTN record states end date of Aug 2012. Project Manager e-mail: "I can confirm that recruitment for the study has not yet finished and that we currently have no DFU’s in the study. We expect that this might change with the possible addition of a new site. We are hoping to have some data by the middle of next year."

ISRCTN90301130

Trial name or titleTreatment of diabetic foot wounds by Vacuum-Assisted Closure (VAC®): A multi-centre randomised controlled trial (KCI)

MethodsRCT

ParticipantsChronic or post-amputation wounds on the feet of people with diabetes

InterventionsNPWT vs conventional moist wound therapy

OutcomesTime to complete healing, percentage of wounds closed, recurrence, resource use, adverse events

Starting dateJune 2011

Contact informationMs D Seidel: doerthe.seidel@uni-wh.de

NotesEnd date cited as Sept 2013

 
Comparison 1. NPWT compared with moist (non-gauze) wound dressings

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Proportion of wounds healed2503Risk Ratio (M-H, Fixed, 95% CI)1.47 [1.18, 1.84]

 2 Time to healing2Hazard Ratio (Fixed, 95% CI)1.85 [1.40, 2.45]

 3 Amputations2503Risk Ratio (M-H, Fixed, 95% CI)0.35 [0.17, 0.74]

 4 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 All adverse events
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Treatment-related adverse events
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. NPWT compared with gauze dressings

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Proportion of wounds healed1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 
Summary of findings for the main comparison. NPWT compared to Moist dressings for healing post-operative wounds in people with diabetes

NPWT compared to Moist dressings for healing post-operative wounds in people with diabetes

Patient or population: patients with healing post-operative wounds in people with diabetes
Settings:
Intervention: NPWT
Comparison: Moist dressings

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Moist dressingsNPWT

Proportion of wounds healed
Follow-up: mean 16 weeks
Study populationRR 1.44
(1.03 to 2.01)
162
(1 study)
⊕⊕⊝⊝
low1,2

388 per 1000559 per 1000
(400 to 780)

Moderate


Time to ulcer healing
Follow-up: mean 16 weeks
Study populationHR 1.91
(1.21 to 2.99)
162
(1 study)
⊕⊕⊝⊝
low1,3

388 per 1000609 per 1000
(448 to 770)

Moderate


Amputation
Follow-up: mean 16 weeks
Study populationRR 0.25
(0.05 to 1.10)
162
(1 study)
⊕⊝⊝⊝
very low1,4

106 per 100026 per 1000
(5 to 116)

Moderate


*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 There was the potential for performance bias as unblinded health professionals were able to make decisions about undertaking closure surgery that could then have resulted more wounds being closed (and classed as healed) or amputated in one group compared with the other.
2 The confidence interval around the estimate of relative risk is consistent with a 3% relative increase in healing with NPWT to a 101% relative increase in healing with NPWT.
3 The confidence interval around the estimate hazard ratio is consistent with a 21% relative increase in the hazard of healing with NPWT to a 199% relative increase in the hazard of healing with NPWT.
4 The confidence interval around the estimate of relative risk is consistent with a 95% relative reduction in chance of healing with NPWT to a 10% relative increase in healing with NPWT.
 
Summary of findings 2. NPWT compared to Moist dressings for debrided foot ulcers in people with diabetes

NPWT compared to Moist dressings for debrided foot ulcers in people with diabetes

Patient or population: patients with debrided foot ulcers in people with diabetes
Settings:
Intervention: NPWT
Comparison: Moist dressings

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Moist dressingsNPWT

Proportion of wounds healed
Follow-up: mean 16 weeks
Low risk of healing1 RR 1.49
(1.11 to 2.01)
341
(1 study)
⊕⊕⊝⊝
low2,3

340 per 1000507 per 1000
(377 to 683)

Moderate risk of healing1

530 per 1000790 per 1000
(588 to 1000)

High risk of healing1

650 per 1000968 per 1000
(722 to 1000)

Time to healing
Follow-up: mean 16 weeks
Low risk of healing4 HR 1.82
(1.27 to 2.60)
341
(1 study)
⊕⊕⊝⊝
low2,5

340 per 1000531 per 1000
(410 to 661)

Moderate risk of healing4

530 per 1000747 per 1000
(617 to 860)

High risk of healing4

650 per 1000852 per 1000
(736 to 935)

Amputation
Follow-up: mean 16 weeks
Study populationRR 0.40
(0.17 to 0.95)
341
(1 study)
⊕⊕⊝⊝
low2,6

101 per 100040 per 1000
(17 to 96)

Moderate


*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Baseline risk of healing obtained from external source in which data from 27,630 patients with a diabetic neuropathic foot ulcer was used to develop a simple prognostic model to predict likelihood of ulcer healing (Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA. Diabetic neuropathic foot ulcers: predicting which ones will not heal. Am J Med. 2003;115:627-31). It is important to note that given an outcome of ulcer healing, low risk refers to a low risk of healing and thus reflects the most severe patient populations. Conversely high risk refers to a high risk of healing.
2 There was the potential for performance bias as unblinded health professionals were able to make decisions about undertaking closure surgery that could then have resulted more wounds being closed (and classed as healed) or amputated in one group compared with the other.
3 The confidence interval around the estimate of relative risk is consistent with a 11% relative increase in healing with NPWT to a 101% relative increase in risk of healing with NPWT.
4 Baseline risk of healing obtained from external source in which data from 27,630 patients with a diabetic neuropathic foot ulcer was used to develop a simple prognostic model to predict likelihood of ulcer healing (Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA. Diabetic neuropathic foot ulcers: predicting which ones will not heal. Am J Med. 2003;115:627-31). It is important to note that given an outcome of ulcer healing, low risk refers to a low risk of healing and thus reflects the most severe patient populations. Conversely high risk refers to a high risk of healing.
5 The confidence interval around the estimate hazard ratio is consistent with a 27% relative increase in the hazard of healing with NPWT to a 160% relative increase in the hazard of healing with NPWT.
6 The confidence interval around the estimate of relative risk is consistent with a 83% relative reduction in amputation risk with NPWT to a 5% relative reduction in amputation risk with NPWT.
 
Summary of findings 3. NPWT compared to Gauze dressings for debrided foot ulcers in people with diabetes

NPWT compared to Gauze dressings for debrided foot ulcers in people with diabetes

Patient or population: patients with debrided foot ulcers in people with diabetes
Settings:
Intervention: NPWT
Comparison: Gauze dressings

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Gauze dressingsNPWT

Proportion of wounds healed
Follow-up: mean 30 days
Low risk of healing1 RR 0.38
(0.05 to 2.59)
15
(1 study)
⊕⊝⊝⊝
very low2,3

340 per 1000129 per 1000
(17 to 881)

Moderate risk of healing1

530 per 1000201 per 1000
(27 to 1000)

High risk of healing1

650 per 1000247 per 1000
(33 to 1000)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Baseline risk of healing obtained from external source in which data from 27,630 patients with a diabetic neuropathic foot ulcer was used to develop a simple prognostic model to predict likelihood of ulcer healing (Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA. Diabetic neuropathic foot ulcers: predicting which ones will not heal. Am J Med. 2003;115:627-31). It is important to note that given an outcome of ulcer healing, low risk refers to a low risk of healing and thus reflects the most severe patient populations. Conversely high risk refers to a high risk of healing.
2 Several domain had unclear risk of bias recorded.
3 The confidence interval around the estimate of relative risk is consistent with a 95% relative reduction in risk of healing with NPWT to a 159% relative increased risk of healing with NPWT.
 
Table 1. Overview of trials

Armstrong 200516 weeksDiabetic foot amputation to trans-metatarsal levelGroup A: moist wound therapy with alginates, hydrocolloid, foam or hydrogel dressings (n = 85)

Group B: NPWT (VAC system, dressing changes every 48 h. Treatment conducted until wound closure or completion of 112-day assessment (n = 77)
Number of wounds completely healed

Group A: 33/85 (38.8%)

Group B: 43/77 (55.8%)

Of healed wounds —healed by secondary intention (without primary/surgical wound closure)

Group A: 25/33 (75.8%)

Group B: 31/43 (72.1%)

Remaining wounds were closed following surgery.

Time to wound healing

median time to healing

Group A: 77 days (IQR 40 to 122)

Group B: 56 days (IQR 26 to 92)

Log rank = p = 0.005

Amputation

Number of participants undergoing further amputation

Group A: 9/85 (10.6%)

Major = 5/Minor = 4

Group B: 2/77 (2.3%)

Major = 0/Minor = 2

There was no difference noted in time to healing for acute or chronic wounds.
Adverse events

Participants who had one or more adverse events

Group A: 46/85 (54.1%)

Group B: 40/77 (51.9%)

Participants who had one or more treatment-related adverse events

Group A: 11/85 (12.9%)

5 classified as serious

Group B: 9/77 (11.7%)

1 classified serious

Resource use

Average total cost per participant

Group A: USD 36,887

Group B: USD26,972

Average total direct cost per participants for those treated for 8 weeks or longer

Group A: USD 36,096

Group B: USD 27,270

Average per participant cost to achieve 100% healing

Group A: USD 38,806

Group B: USD 25,954

Blume 200816 weeksUlceration of the foot in people with diabetesGroup A: advanced moist wound therapy dressings used according to guidelines/local protocols (n = 169)

Group B: NPWT (VAC system), applied according to manufacturer’s instructions. (n = 172)
Number of wounds completely healed (six participants excluded in paper as did not receive treatment, added back into denominator here)

Group A: 48/169 (28.4%)

Group B: 73/172 (42.4%)

Proportion of wounds closed using surgery (unclear if considered part of healed group)

Group A: 14/169 (8.3%)

Group B: 16/172 (9.3%)

Time to wound healing

median time to healing

Group A: could not be estimated

Group B: 96 days (95% CI 75.0 to 114.0)

Log rank taken as P value 0.001

Amputation

Number of participants undergoing amputation*

Group A: 17/169 (10.1%)

Major = 4; minor = 13

Group B: 7/172 (4.1%)

Major = 5; minor = 2
Adverse events

Limited data: not extracted

Resource use – taken from conference abstract that we think is related to this main publication.

Mean estimated total costs of inpatient services per participant

Group A: USD 8570 (95%CI USD 5922 to USD 11,432)

Group B: USD 5206 (95%CI USD 3172 to USD 7561)

Karatepe 2011Not specified. Last assessment one month after healingDiabetic foot ulcersGroup A: conventional wound care treatment: based on text in report taken to be dry gauze (n = 37)

Group B: NPWT (VAC system) (n = 30)
Time to healing

Median time to healing

Group A: 4.4 weeks

Group B: 3.9 weeks

Mean value presented but not extracted.

No specific P value presented
Health-related quality of life

SF-36: Data not presented.

Mody 2008Not specified: until healing or loss to follow-upDiabetic foot ulcersGroup A: wet-to-dry gauze (n = 9)

Group B: locally-constructed NPWT (n = 6)
Number of wounds completely healed

By secondary intention:

Group A: 1/9 (11.0%)

Group B: 1/6 (16.6%)

By delayed primary closure:

Group A: 3/9 (33%)

Group B: 0/6 (0%)

Novinščak 20102 monthsComplicated diabetic foot ulcersGroup A: classic gauze (n = 8)

Group B: dressings (moist) (n = 12)
Group C: NPWT (n = 7)
Healing rate (percentage with wound closure – defined by author on contact)

Group A: 4/8* (50%)

Group B: 9/12* (75%)

Group C: * could not be calculated (90%)

*Figure calculated by review author as only proportions obtained from study author