Table 5Characteristics of included studies

AuthorTotal no. of patientsInterventionsDosageFollow-up periodPrimary outcomes
Growth factors
Granulocyte colony-stimulating factor (G-CSF)
de Lalla et al. (2001)40G-CSF + standard care vs. standard care only (control).
Standard care = standard wound care + antibiotics.
263 micrograms subcutaneously daily for 21 days.9 weeks, then 6 monthsAmputation; overall need for surgical interventions; improvement on infection status; treatment-related AEs
Gough et al. (1997)40G-CSF + standard care vs. placebo + standard care only (control).
Standard care = standard wound care + antibiotics.
5 micrograms/kg daily for 7 days.7 days treatment, follow-up unclear.Amputation; complete wound healing; overall need for surgical interventions; resolution of infection; improvement on infection status; treatment-related AEs
Kastenbauer et al. (2003)40G-CSF + standard care vs. placebo + standard care only (control).
Standard care = standard wound care + antibiotics.
5 micrograms/kg daily for 10 days.10 days treatment, follow-up unclear.Amputation; complete wound healing; overall need for surgical interventions; improvement on infection status; treatment-related AEs
Viswanathan et al. (2003)20G-CSF + standard care vs. placebo + standard care only (control).
Standard care = standard wound care + antibiotics.
5 micrograms/kg daily for 7 days.7 days treatment, follow-up unclear.Amputation; overall need for surgical interventions; length of hospital stay (days); improvement on infection status
Yonem et al. (2001)30G-CSF + standard care vs. standard care only (control).
Standard care = standard wound care + antibiotics.
5 micrograms/kg daily for 3 or more days.Unclear.Amputation; overall need for surgical interventions; length of hospital stay (days)
Platelet-derived growth factor (PDGF)
D'Hemecourt et al. (2005)112PDGF + standard care vs. standard care only (control).
Standard care = debridement, dressing, off-loading.
100 micrograms/g becaplermin gel, change daily.20 weeksComplete wound healing; withdrawal due to treatment-related AEs; at least 1 treatment-related AEs
Hardikar et al. (2005)110PDGF + standard care vs. standard care only (control).
Standard care = debridement, dressing, off-loading.
0.01% gel with 100 micrograms of rhPDGF-BB/g.10 weeks, then 20 weeks follow-upComplete wound healing; mean healing time
Robson et al. (2005)146PDGF + standard care vs. standard care only (control).
Standard care = debridement, adaptic dressing, off-loading.
0.01% becaplermin gel, change daily, over 20 weeks.20 weeksComplete wound healing
Wieman et al. (1998)383PDGF + standard care vs. placebo + standard care (control).
Standard care = debridement, dressing, off-loading.
0.01% Becaplermin gel 30 micrograms or 100 micrograms daily, over 20 weeks.20 weeks than 3 monthsComplete wound healing; withdrawal due to treatment-related AEs
Epidermal growth factor (EGF)
Afshari et al. (2005)50EGF + standard care vs. placebo + standard care only (control).
Standard care = debridement, dressing.
1 mg of EGF/1000 mg of 1% silver sulfadiazine, once a day for 28 days.4 weeksLength of hospital stay (days); complete wound healing
Fernandez-Montequinn et al. (2009)149EGF + standard care vs. standard care only (control). Standard care = debridement, dressing, off-loading.25 or 75 micrograms rhEGF in 5ml water for injection, daily for 2 weeks.2 weeksAt least 50% wound reduction; treatment-related AEs - burning sensation; treatment-related AEs -shivering
Tsang et al. (2003)59EGF + standard care vs. standard care only (control). Standard care = Actovegin cream, debridement, dressing.0.02% or 0.04% [wt/wt] hEGF cream + 5% Actovegin cream, daily for 12 weeks.12 weeks then 24 weeksAmputation; complete wound healing
Viswanathan et al. (2006)57EGF vs. placebo
(no mention of standard wound care).
150 micrograms rhEGF cream, twice daily, for 15 weeks.15 weeksComplete wound healing.
Transforming growth factor beta (TGF-β)
Robson et al. (2000)155TGF-β + standard care vs. standard care only (control). Standard care = debridement, dressing, off-loading.Topical collagen sponges contained TGF-β 0.05 micrograms/cm2, 0.5 micrograms/cm2, or 5.0 micrograms/cm2, twice weekly, for 21 weeks.21 weeksComplete wound closure.
Hyperbaric oxygen therapy (HBOT)
Abidia et al. (2003)18HBOT vs. specialised wound management alone.At 2.4 ATA for 90 mins on 30 occasions over 6 weeks.6 weeksMajor amputation; minor amputation; complete wound healing
Doctor et al. (1992)30HBOT + standard care vs. standard care only (control).
Standard care = dressing and debridement.
At 3.0 ATA on 4 occasions over 6 weeks.4 weeksMajor amputation; minor amputation
Duzgun et al. (2008)100HBOT + standard care vs. standard care only (control).
Standard care = dressing and debridement.
At 2.0 to 3.0 ATA for 90 mins, twice a day, followed by once a day (alternating) for a period of 20 to 30 days.20 to 30 daysMajor amputation; minor amputation; complete wound healing; required surgical interventions
Faglia et al. (1996)70HBOT vs. specialised wound management alone.At 2.2 to 2.5 ATA for 90 mins on 39 occasions over 6 weeks.6 weeksMajor amputation
Kessler et al. (2003)27HBOT + standard care vs. standard care only (control).
Standard care = off-loading.
At 2.5 ATA for 90 mins, twice a day, 5 days per week for 2 weeks.2 weeks, than 1 month follow-upComplete wound healing; mean reduction of ulcer surface area
Londahl et al. (2010)90HBOT + standard care vs. sham HBOT + standard care

Standard care = antibiotic treatment, revascularisation, debridement, off-loading, and metabolic control.
At 2.5 ATA for 90 mins, 5 days per weeks for 8 to 10 weeks, no more than 40 sessions.1 yearMajor amputation; complete wound healing
Dermal or skin substitutes (DSS)
Caravaggi et al. (1996)79DSS + standard care vs. non-adherent paraffin gauze + standard care.
Standard care = debridement and off-loading.
1 or 2 applications for 7 to 10 days.11 weeksComplete wound healing; withdrawal due to ulcer-related AEs; overall ulcer-related AEs
Gentzknow et al. (1996)25DSS + standard care vs. moistened gauze + standard care.
Standard care = debridement and off-loading.
1 application weekly for a total of 8 applications.12 weeksComplete wound healing; at least 50% wound closure; overall ulcer-related AEs
Marston et al. (2003)245DSS + standard care vs. moistened gauze + standard care.
Standard care = debridement and off-loading.
Up to 7 applications weekly.12 weeksComplete wound healing; required surgical interventions; overall ulcer-related AEs
Naughton et al. (1997)281DSS + standard care vs. moistened gauze + standard care.
Standard care = debridement and off-loading.
8 applications weekly.12 weeksComplete wound healing
Pham et al. (1999)33DSS + standard care vs. moistened gauze + standard care.
Standard care = debridement and off-loading.
Maximum 5 applications from week to week 4.12 weeksComplete wound healing
Veves et al. (2001)208DSS + standard care vs. moistened gauze + standard care.
Standard care = debridement and off-loading.
Maximum 5 applications from week to week 4.12 weeksComplete wound healing; median time to complete closure; withdrawal due to ulcer-related AEs; overall ulcer-related AEs
Puttirutvong et al. (2004)80Meshed skin graft + standard care vs. split thickness skin graft + standard care
Standard care = daily dressing
Unclear6 monthsMean healing time.
Negative pressure wound therapy (NPWT)
Blume et al. (2008)335NPWT + standard care vs. moist wound therapy + standard care (control).
Standard care = off-loading.
Change every 48 to 72 hours.16 weeksAmputation; complete wound closure; median time to 75% wound closure; overall ulcer-related AEs.
Etoz et al. (2004)24NPWT vs. saline moistened gauze (control)Change every 48 hours.12 to 20 daysMean reduction wound surface area (cm2).
Williams et al. (2005)162NPWT + standard care vs. moist wound therapy + standard care (control).
Standard care = off-loading.
Change every 48 hours.16 weeksAmputation; complete wound closure; median time to achieve 75–100% granulation; overall treatment-related AEs.
Other adjunctive treatments
Electrical stimulation therapy
Moretti et al. (2009)30External shock wave therapy + standard care vs. standard care only (control).
Standard care = debridement, off-loading, antibiotics if needed.
3 sessions (1 or 2 mins) per day, with 0.03 mJ/mm2 using electromagnetic lithotripter.20 weeksComplete wound healing, mean healing time (days)
Peters et al. (2001)40Electrical stimulation vs. placebo stimulation with no current (control).50V with 80 twin peaks per second, every night for 8 hours.12 weeksComplete wound healing.
Autologous platelet-rich plasma gel
Driver et al. (2006)72Autologous platelet-rich plasma gel + standard care vs. saline gel + standard care only (control).
Standard care = dressing, off-loading.
Unclear.12 weeksComplete wound healing, median time to complete wound closure.
Acellular dermal regenerative tissue matrix
Reyzelman et al. (2009)85Acellular dermal matrix + standard care vs. standard care only (control).
Standard care = debridement, dressing, off-loading.
Single application.12 weeksComplete wound healing, healing rate (adjusted hazard ratio).
RGD peptide matrix
Steed et al. (1995)65RGD peptide matrix + standard care vs. saline gauze + standard care only (control).
Standard care = debridement, dressing.
Twice per week10 weeksComplete wound healing
OASIS wound matrix vs. PDGF
Niezgoda et al. (2005)73OASIS wound matrix + standard care vs. PDGF + standard care.
Standard care = debridement, off-loading.
OASIS = clinician to decide on weekly basis to change or not.
PDGF = applied weekly for 12 hours.
12 weeksComplete wound healing, ulcer recurrence.
Dalteparin (injection) (for diabetic patients with peripheral arterial occlusive disease)
Kalani et al. (2003).85Dalteparin (injection) + standard care vs. placebo saline + standard care.
Standard care = dressing, debridement, off-loading, antibiotic if required.
0.2 ml (Fragmin, 25000 units/ml) for maximum of 6 months.6 monthsAmputation, complete wound healing, at least 50% wound reduction.

AE = adverse events; ATA = absolute atmospheres; RGD = arginine-glycine-aspartic acid; rhEGF = recombinant human epidermal growth factor.

From: 3, Evidence review and recommendations

Cover of Diabetic Foot Problems
Diabetic Foot Problems: Inpatient Management of Diabetic Foot Problems.
NICE Clinical Guidelines, No. 119.
Centre for Clinical Practice at NICE (UK).
Copyright © 2011, National Institute for Health and Clinical Excellence.

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