Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review Evidence-based Synthesis Program APPENDIX D. EVIDENCE TABLES Table 1. Study Characteristics Table Study, Year Intervention Patient Characteristics Country Inclusion/Exclusion Criteria Comparator Study Quality Ulcer Type Funding Source Length of Follow-up Abidia 200349 Inclusion: diabetes; ischemic lower extremity N=16 (of 18 randomized) Intervention (n=9): HBOT; 2.4 ATA Allocation concealment: ulcers (>1 cm and <10 cm in maximum Age (years): 71 for 90 minutes on 30 occasions Adequate United Kingdom diameter); no signs of healing for >6 weeks Gender (% male): 50 over 6 weeks; multi-place chamber despite optimum medical management; Race/ethnicity: NR Blinding: Patients, Funding Source: NR occlusive arterial disease confirmed by ankle- BMI: NR Control (n=9): sham (hyperbaric investigators, outcome brachial pressure index <0.8 (or great toe <0.7 if Pre-albumin: NR air) assessors Therapy Type: calf vessels incompressible) HbA1c (%): NR ALL: specialized multidisciplinary Intention to treat analysis Hyperbaric oxygen Smoking: 19% wound management program (ITT): No, two withdrawals (HBOT) Exclusion: planned vascular surgery, # Work days missed: NR (off-loading, debridement, moist not included in analysis angioplasty, or thrombolysis ABI: <0.8 for inclusion dressing) Wound location: foot Withdrawals/dropouts Wound type: ischemic diabetic Antibiotic Use: As needed adequately described: Yes Wound size, mm2 (median): HBOT 106; Treatment Duration: 6 weeks control 78 Follow-up Duration: 1 year Wound grade (Wagner*, %): Grade I 6; Study Withdrawal (%): 20 (n=2) II 94 Treatment Compliance: “The Wound duration, months: HBOT 6; protocol was strictly followed control 9 throughout the study” Comorbid conditions (%): History of CAD/CVD: (previous bypass 31, angioplasty 6) History of DM: 100 History of amputation: minor 19 112 Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review Evidence-based Synthesis Program Study, Year Intervention Patient Characteristics Country Inclusion/Exclusion Criteria Comparator Study Quality Ulcer Type Funding Source Length of Follow-up Agrawal 200928 Inclusion: ≥30 years of age; Wagner stage I, II, N=28 Intervention (n=14): rhPDGF 0.01% Allocation concealment: III, or IV ulcers; foot ulcer duration >3 months; Age (years): 55 gel at 2.2ug/cm2/day Unclear India free of infection; adequate lower-limb blood Gender (% male): 68 supply (transcutaneous oxygen tension ≥30 Race/ethnicity: NR Comparator (n=14): placebo gel at Blinding: Unclear Funding Source: NR 2.2ug/cm2/day mmHg), no or moderate peripheral vascular BMI: 25.7 Intention to treat analysis Therapy Type: disease Pre-albumin: NR ALL: standard regimen of high- (ITT): No Platelet-derived HbA1c (%): 8.8 quality care (included glycemic Growth Factor Exclusion: active neoplastic disease; diagnosis Smoking: NR Withdrawals/dropouts of active infection characterized by warmth, control, debridement, dressings, # Work days missed: NR pressure relief) adequately described: erythema, lymphangitis, lymphadenopathy, ABI: NR Partial – 5 withdrawals oedema, or pain; received immunosuppressive Wound location: foot Antibiotic Use: as needed from the control group therapy during the preceding three months; Wound type: diabetic Treatment Duration: 12 weeks with no reason for liver disease, pulmonary tuberculosis, Wound size: 41.5 cm2 (ulcer size Follow-up Duration: NR withdrawal thyroid disorder uremia, alcoholism or significantly larger in study group Study Withdrawal (%): 18 (all from renal insufficiency; undergoing vascular p=0.003) control group at week 12) reconstruction or receiving steroid or Wound grade: NR Treatment Compliance: NR anticoagulant therapy Wound duration: NR Infection: excluded Comorbid conditions (%): Diabetes: 100 Aminian 200027 Inclusion: chronic non-healing diabetic ulcers N=12 ulcers (7 patients) of 14 ulcers (9 Intervention (n=7 ulcers): Allocation concealment: of at least eight weeks duration; controlled patients) randomized autologous platelet extract (APE) Inadequate Iran blood sugar; normal peripheral blood platelet Age (years): 60 + silver sulfadiazine dressing 12 Blinding: Unclear Funding Source: count (>150,000/cu mm); negative history of Gender (% male): 100 hours on and 12 hours off malignancy Race/ethnicity: NR Government Comparator (n=5 ulcers): saline Intention to treat analysis BMI: NR (ITT): No Therapy Type: Exclusion: determined to have non-diabetic Pre-albumin: NR solution and silver sulfadiazine 12 Platelet-Derived ulcers hours on and 12 hours off Withdrawals/dropouts HbA1c (%): NR Growth Factor Smoking: NR ALL: supportive, conventional care adequately described: Yes # Work days missed: NR (debridement, blood sugar checked – 2 patients with 2 ulcers ABI: NR weekly, off-loading) excluded after entering Wound location: foot study (non-compliance, Wound type: diabetic ulcer Antibiotic Use: oral, if needed non-diabetic ulcer) Wound size: 5.9 cm2 Treatment Duration: 8 weeks Wound grade: NR Follow-up Duration: NR Wound duration: 12.9 wks Study Withdrawal (%): 22% Infection: NR Treatment Compliance: 1/9 pts Comorbid conditions (%): withdrawn for non-compliance Diabetes: 100 113 Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review Evidence-based Synthesis Program Study, Year Intervention Patient Characteristics Country Inclusion/Exclusion Criteria Comparator Study Quality Ulcer Type Funding Source Length of Follow-up Armstrong 200581 Inclusion: age ≥18; wound from diabetic foot N=162 Intervention (n=77): VAC system; Allocation concealment: Apelqvist 200882 amputation to transmetatarsal level of foot; Age (years): 59 dressing changes every 48 hrs Adequate evidence of adequate perfusion (transcutaneous Gender (% male): 81 United States (18 Comparator (n=85): standard Blinding: Partial O2 on dorsum of foot ≥30 mmHg or ABI ≥0.7 Race/ethnicity (%): Non-Hispanic white: sites) care (moist wound therapy with (independently assessed and ≤1.2, and toe pressure ≥30 mmHg); 48; African-American: 17; Mexican- alginates, hydrocolloids, foams, or and confirmed closure Funding Source: University of Texas grade 2 or 3 in depth American: 32; Native American: 3 hydrogels; dressing changes every with digital planimetry) Industry (not involved BMI: 31 Exclusion: active Charcot arthropathy of day unless otherwise advised in analysis or write-up Pre-albumin (g/L): 0.19 Intention to treat foot; wound from burn, venous insufficiency, of manuscript; did not HbA c (%): 8.2 ALL: off-loading therapy as analysis (ITT): Yes – no untreated cellulitis or osteomyelitis, collagen 1 maintain veto power Smoking: 9% indicated; sharp debridement at withdrawals vascular disease, malignant disease, or over final article) # Work days missed: NR randomization and as needed uncontrolled hyperglycemia (HbA c >12%); 1 ABI: 1.1 Withdrawals/dropouts treated with corticosteroids, immunosuppressive Therapy Type: Wound location: foot Antibiotic Use: NR adequately described: Yes drugs, or chemotherapy; VAC therapy in past Negative Pressure Wound type: amputation Treatment Duration: wound closure – no withdrawals 30 days, present or previous (past 30 days) Wound Therapy Wound size: 20.7 cm2 or 112 days treatment with growth factors; normothermic Wound grade: U of Texas 2/3 Wound Follow-up Duration: none therapy, hyperbaric medicine, or bioengineered duration: 1.5 months Study Withdrawal (%): 0 tissue Comorbid conditions (%): Treatment Compliance: NR History of DM: 100 (90% T2) Belcaro 201038 Inclusion: Venous Ulcer Patients: N=82 Intervention (n=44 VU, n=34 Allocation concealment: Venous Ulcer (VU) Patients: chronic venous Age (years): 47 DU): silver ointment around and Unclear Italy ulcers, venous microangiopathy, and peri- Gender (% male): 46 at edges of ulcerated area twice Blinding: Unclear Funding Source: NR malleaolar ulcerations Diabetic Ulcer Patients: N=66 daily after noninvasive washing; Diabetic Ulcer (DU) Patients: diabetic Age (years): 55.9 bandage and elastic stocking Intention to treat Therapy Type: Silver microangiopathy and plantar ulcers due Gender (% male): 44 analysis (ITT): Yes (no Oxide Ointment Comparator (n=38 VU, n=32 to reduced arterial pressure, diabetic Both Groups: withdrawals) DU): cleansing & wound care; microangiopahty and neuropathy, and localized Race/ethnicity: NR compression (mild for DU) infection BMI: NR Withdrawals/dropouts adequately described: Yes Pre-albumin: NR Antibiotic Use: NR Exclusion: (none) HbA c (%): NR Treatment Duration: 4 weeks Venous Ulcer Patients: venous thrombosis or 1 Smoking: NR Follow-up Duration: No follow-up arterial problems in past year; severe ischemia # Work days missed: NR post tx and necrosis (based on Doppler detected tibial ABI: NR Study Withdrawal (%): 0 pulse) Wound location: plantar (DU) Treatment Compliance: NR Diabetic Ulcer Patients: none reported Wound type: venous, diabetic Wound size: VU 3.2 cm2, DU 2.2 cm2 Wound grade: NR Wound duration: NR Comorbid conditions (%): NR 114 Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review Evidence-based Synthesis Program Study, Year Intervention Patient Characteristics Country Inclusion/Exclusion Criteria Comparator Study Quality Ulcer Type Funding Source Length of Follow-up Bhansali 200930 Inclusion: >20 years old with type 1 or 2 N=20 (24 ulcers) Intervention (n=13): 0.01% rh- Allocation concealment: diabetes; at least one