Skin Substitutes for Chronic Wounds (PDF) Form

Patients receiving skin replacement surgery with a skin substitute graft should be under the care of a wound care physician or surgeon. It is imperative that systemic disease be monitored/treated to ensure adequate healing of the wound site. This policy addresses the medical necessity criteria for skin substitutes in the treatment of chronic wounds. Note: For skin substitutes for burns, refer to CP.MP.186 Burn Surgery. Policy/Criteria
I. It is the policy of health plans affiliated with Centene Corporation® that skin substitutes are medically necessary for diabetic foot ulcers, v enous stasis ulcers, or venous leg ulcers when
all of the following criteria are met:
A. Age ≥ 18 years, or diabetic (Type 1 or Type 2);
B. Wound is chronic, defined as a wound that does not respond to at least 4 weeks of
standard wound treatment as a component of organized, comprehensive, conservative therapy;
C. Wound characteristics and treatment plan are documented;
D. Standard wound care has failed, evidenced by all of the following:

1. The ulcer or skin deficit has been treated with appropriate wound-care measures,
   including debridement, standard dressings (including silver dressings), compression, off-loading;
2. Wound has increased in size or depth; or has not changed in baseline size or depth
   and there is no indication that improvement is likely (such as granulation, epithelialization or progress towards closing);
   E. Documentation of effort to cease nicotine use, including from sources other than excluding nicotine replacement therapy, for at least 4 weeks during cigarettes, but conservative wound care and prior to planned bioengineered skin replacement therapy, or
   no nicotine use;
   F. Wound characteristics, all of the following:
3. Partial- or full-thickness ulcer with a clean, granular base;
   
   2. No involvement of tendon, muscle, joint capsule, or exposed bone or sinus tracts, unless Integra® is used per FDA guidelines;

4. No wound infection; wound must be clean and free of necrotic debris or exudate;

   4. Member/enrollee has adequate circulation/oxygenation to support tissue
      growth/wound healing, a s evidenced by physical examination (e.g., Ankle-Brachial
      Index [ABI] of no less than 0.7 or TCOM pressure greater than 30 millimeters of
      mercury [mmHg]);
      G. For lower extremity chronic wounds (diabetic foot ulcer or venous leg ulcer), one of the
      following:
   5. Diabetic foot ulcer (DFU), and all of the following:
      Page 1 of 10

   CLINICAL POLICY Skin Substitutes a. Hgb A1c of ≤ 8 or documentation of improving control; b. Documented conservative wound care for ≥ 4 weeks; c. Wound is without evidence of osteomyelitis or nidus of infection;

5. Venous stasis ulcer (VSU) or venous leg ulcers (VLU), all of the following: a. A chronic, non-infected ulcer VSU or VLU has failed to respond to documented conservative wound-care measures for ≥ 4 weeks with documented compliance; b. Completed assessment includes: i. History (prior ulcers, thrombosis risks); ii. Physical exam (edema, skin changes); iii. ABI (Ankle-Brachial Index) and duplex scan to confirm Clinical-Etiology- Anatomy-Pathophysiology (*CEAP); c. If VLU is present, a venous duplex ultrasound has been completed to assess saphenous vein incompetency/venous reflux and contributory superficial ulcer bed perforators;
6. Full thickness skin-loss ulcer is the result of abscess, injury or trauma and has failed to respond to appropriate control of infection, foreign body, tumor resection, or other disease process for ≥ 4 weeks; H. Requested applications comply with FDA guidelines for the specific product, not to exceed 10 applications or treatments; I. Only one skin substitute will be simultaneously in place per wound episode. Product change within the wound episode is allowed, not to exceed the 10 application limit per wound per 12 week episode of care; J. None of the following contraindications:
7. Inadequate control of underlying conditions or exacerbating factors (e.g., uncontrolled diabetes with Hgb A1c > 8%, or no documented improvement of glucose levels in the last 4 weeks, active infection, and active Charcot arthropathy of the ulcer surface, vasculitis or continued tobacco smoking without physician attempt to affect smoking cessation);
8. Known hypersensitivity to any component of the specific skin substitute graft (e.g., allergy to avian, bovine, porcine, equine products);

9. Partial thickness loss with the retention of epithelial appendages (epithelium will repopulate the deficit). Note: Treatment of any chronic skin wound will typically last no more than 12 weeks. II. It is the policy of health plans affiliated with Centene Corporation that skin substitutes are not medically necessary for the following indications or scenarios: A. All indications not noted in Policy/criteria I; B. Decubitus (pressure) ulcer treatment; C. Continued skin substitute use after treatment failure, which is defined as the repeat or alternative application course (of up to 12 weeks) of skin substitute grafts within one year of any given course of skin substitute treatment for a venous stasis ulcer or diabetic foot ulcer; D. Retreatment of healed ulcers (those showing greater than 75% size reduction and smaller than 1 square cm). Page 2 of 10

   CLINICAL POLICY Skin Substitutes Background
   According to the Centers for Medicare & Medicaid Services (CMS), chronic wounds of the lower extremities, including venous stasis ulcers (VSU), venous leg ulcers (VLU), diabetic foot ulcers (DFU) and pressure sores, are a major public health problem. While lower extremity ulcers have numerous causes, such as burns, trauma, mixed venous-arterial disease, immobility and vasculitis, nutritional or other neuropathy, over 90% of the lesions in the United States are related to venous stasis disease and diabetic neuropathy.1 These wounds frequently require detailed interventions to start the healing process again; furthermore, patients experience significant functional loss, wound recurrence, and increased morbidity.6 Standard care for lower extremity wounds and ulcers includes infection control, management of edema, mechanical offloading of the affected limb, mechanical compression, limb elevation, debridement of necrotic tissue, management of systemic disease and counseling on the risk of continued tobacco use. Additionally, maintenance of a therapeutic wound environment with appropriate dressings can facilitate development of healthy granulation tissue and re- epithelialization. Dressings are essential to wound management because the appropriate dressing not only maintains the moisture balance within the wound, but the dressing also controls exudate, which protects the wound from additional trauma.1,2 A wound that has not healed within one to three months may be considered a chronic wound and can be a challenge to treat effectively. Even with advancements in standard wound care and synthetic occlusive dressings, some ulcers fail to heal and may benefit from a skin substitute.1,2 Skin substitutes promote wound healing by replacing extracellular matrix.7 Skin substitutes are categorized based on the composition of epidermal, dermal, and composite skin present.7 They are heterogeneous and can be largely separated into two primary categories: cellular (comprised of living cells); or acellular (composed of synthetic materials or tissue from which living cells have been removed).8,9 The categories are further split based on composition and source of material, including xenograft, acellular allograft, cellular allograft, autograft and synthetic skin substitute choices.7 For VLU, an evaluation for the presence of saphenous vein reflux is essential prior to consideration of skin substitutes. If there is significant saphenous vein incompetency and reflux (valve closure time defined as > 500 milliseconds), or if ulcer bed veins are identified as contributory on ultrasound, a referral to a vascular surgeon or interventional radiologist is required. Endovascular laser or radiofrequency ablation can enhance rates of healing compared to other treatments for significant saphenous vein reflux. Without significant reflux, sclerotherapy may also be more beneficial.3 According to a 2016 Cochrane review, the overall therapeutic outcome of skin grafts and tissue replacements used with standard wound care demonstrated an increase in the healing rate of foot ulcers and slightly fewer amputations in patients with diabetes compared with standard wound care alone.10 The Wound Healing Society updated their guidelines in 2016, indicating that cellular and acellular skin equivalents positively affect healing in diabetic ulcers by “releasing therapeutic amounts of growth factors, cytokines, and other proteins that stimulate the wound bed.”11 Page 3 of 10

   CLINICAL POLICY Skin Substitutes There are currently a wide variety of bioengineered products available for soft tissue coverage to affect closure.6 Autologous skin grafts, also referred to as autografts, are permanent covers that use skin from different parts of the individual’s body. These grafts consist of the epidermis and a dermal component of variable thickness. A split-thickness skin graft (STSG) includes the entire epidermis and a portion of the dermis. A full thickness skin graft (FTSG) includes all layers of the skin. Although autografts are the optimal choice for full thickness wound coverage, areas for skin harvesting may be limited, particularly in cases of large burns or venous stasis ulceration. Harvesting procedures are painful, disfiguring and require additional wound care.2,4 Allografts, which use skin from another human (e.g., cadaver), and Xenografts, which use skin from another species (e.g., porcine or bovine), may also be employed as temporary skin replacements. However, they must later be replaced by an autograft or the ingrowth of the patient’s own skin.2,4 Bioengineered Skin and Cultured Epidermal Autografts (CEA) are autografts derived from the patient’s own skin cells grown or cultured from very small amounts of skin or hair follicle. Production time is prolonged. One such product is grown on a layer of irradiated mouse cells, displaying some components of a xenograft. Widespread usage has not been available due to limited availability or access to the technology.2,4 Coding Implications
   This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2021, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage.
   Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. CPT® Codes 15271 15272 15273 15274

   Application of skin substitute graft to trunk, arms, legs, total wound surface area up to 100 sq cm; first 25 sq cm or less wound surface area Application of skin substitute graft to trunk, arms, legs, total wound surface area up to 100 sq cm; each additional 25 sq cm wound surface area, or part thereof (List separately in addition to code for primary procedure) Application of skin substitute graft to trunk, arms, legs, total wound surface area greater than or equal to 100 sq cm; first 100 sq cm wound surface area, or 1% of body area of infants and children Application of skin substitute graft to trunk, arms, legs, total wound surface area greater than or equal to 100 sq cm; each additional 100 sq cm wound surface area, or part thereof, or each additional 1% of body area of infants and Page 4 of 10

   CLINICAL POLICY Skin Substitutes CPT® Codes 15275 15276 15277 15278 HCPCS®* Codes A2001 A2002 A2003 A2004 A2005 A2006 A2007 A2008 A2009 A2010 Q4100 Q4101 Q4102 Q4103 Q4104 Q4105 Q4106 Q4107 Q4108 Q4110

   children, or part thereof (List separately in addition to code for primary procedure) Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up to 100 sq cm; first 25 sq cm or less wound surface area Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up to 100 sq cm; each additional 25 sq cm wound surface area, or part thereof (List separately in addition to code for primary procedure) Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area greater than or equal to 100 sq cm; first 100 sq cm wound surface area, or 1% of body area of infants and children Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area greater than or equal to 100 sq cm; each additional 100 sq cm wound surface area, or part thereof, or each additional 1% of body area of infants and children, or part thereof (List separately in addition to code for primary procedure)

   InnovaMatrix AC, per sq cm Mirragen Advanced Wound Matrix, per sq cm bio-ConneKt Wound Matrix, per sq cm XCelliStem, per sq cm Microlyte Matrix, per sq cm NovoSorb SynPath dermal matrix, per sq cm Restrata, per sq cm TheraGenesis, per sq cm Symphony, per sq cm Apis, per sq cm Skin substitute, nos Apligraf, per sq cm Oasis wound matrix, per sq cm Oasis burn matrix, per sq cm Integra bilayer matrix wound dressing (BMWD), per sq cm Integra dermal regeneration template (DRT) or Integra Omnigraft dermal regeneration matrix, per sq cm Dermagraft, per sq cm Graftjacket, per square centimeter Integra matrix, per sq cm Primatrix, per square centimeter Page 5 of 10

   CLINICAL POLICY Skin Substitutes HCPCS®* Codes Q4111 Q4115 Q4117 Q4118 Q4121 Q4122 Q4123 Q4124 Q4126 Q4127 Q4128 Q4132 Q4133 Q4134 Q4135 Q4136 Q4137 Q4140 Q4141 Q4146 Q4147 Q4148 Q4151 Q4152 Q4153 Q4154 Q4156 Q4157 Q4158 Q4159 Q4160 Q4161 Q4163 Q4164 Q4165 Q4166 Q4169 Q4170 Q4173 Q4175 Q4176 Q4178 Q4180

   Gammagraft, per sq cm Alloskin, per sq cm Hyalomatrix, per sq cm Matristem micromatrix, 1mg TheraSkin, per sq cm DermACELL, DermACELL AWM or DermACELL AWM Porous, per sq cmr AlloSkin RT, per sq cm Oasis ultra tri-layer wound matrix, per sq cm MemoDerm, DermaSpan, TranZgraft or InteguPly, per sq cm Talymed, per sq cm FlexHD, or AllopatchHD, per sq cm Grafix Core and GrafixPL Core, per sq cm Grafix PRIME, GrafixPL PRIME, Stravix and StravixPL, per sq cm Hmatrix, per sq cm Mediskin, per sq cm E-Z Derm, per sq cm Amnioexcel, amnioexcel plus or biodexcel, per square centimeter BioDFence, per square centimeter Alloskin AC, per square centimeter Tensix, per square centimeter Architect, Architect PX, or Architect FX, extracellular matrix, per square centimeter Neox Cord 1K, Neox Cord RT, or Clarix Cord 1K, per square centimeter AmnioBand or Guardian, per sq cm DermaPure, per sq cm Dermavest and Plurivest, per sq cm Biovance, per sq cm Neox 100 or Clarix 100, per sq cm Revitalon, per sq cm Kerecis Omega3, per sq cm Affinity, per sq cm Nushield, per square centimeter bio-ConneKt wound matrix, per sq cm Woundex, bioskin, per sq cm Helicoll, per square cm Keramatrix or Kerasorb, per sq cm Cytal, per square centimeter Artacent wound, per sq cm Cygnus, per sq cm Palingen or Palingen Xplus, per sq cm Miroderm, per sq cm Neopatch or therion, per square centimeter FlowerAmnioPatch, per sq cm Revita, per sq cm Page 6 of 10

   CLINICAL POLICY Skin Substitutes HCPCS®* Codes Q4184 Q4186 Q4187 Q4188 Q4195 Q4196 Q4197 Q4199 Q4201 Q4203 Q4232 Q4237 Q4238 Q4239 Q4254

   Cellesta or Cellesta Duo, per sq cm Epifix, per square centimeter Epicord, per square centimeter AmnioArmor, per sq cm PuraPly, per square cm PuraPly AM , per square cm Puraply XT, per square cm Cygnus matrix, per sq cm Matrion, per sq cm Derma-Gide, per sq cm Corplex, per sq cm Cryo-Cord, per sq cm Derm-Maxx, per sq cm Amnio-Maxx or Amnio-Maxx Lite, per sq cm Novafix DL, per sq cm Reviews, Revisions, and Approvals Policy adapted from WellCare’s HS433 Skin Substitutes policy. Removed description information about identification of MD managing chronic conditions. Removed requirement for MD review of all requests. Rearranged some not medically necessary indications into the contraindications section. In I.D, changed requirement for no nicotine use for at least 4 weeks to documentation of effort to cease nicotine use, or no nicotine use for at least 4 weeks. In the diabetic foot ulcer criteria, removed requirement of neuropathy. In I.I.1, changed contraindication of “active Charcot arthropathy of the ulcer extremity” to “active Charcot arthropathy of the ulcer surface.” In DFU section, removed documentation of assessment of physical activity, nutrition, physical exam, check of prosthetics, and history of diabetes management, including comorbidities. Changed requirement of HbA1c ≤7% to ≤8%, or with documented improvement of blood glucose in last 4 weeks. Changed HbA1c contraindication to >8% or with no document improvement of blood glucose in last 4 weeks. Reworded some extraneous language with no clinical significance. Removed criteria stating that switching products during an episode of wound care is not allowed. Removed not medically necessary language about repeated billing of surgical preparation services. Revised name of the policy to Skin Substitutes for Chronic Wounds.
   Added criteria of age ≥ 18 years, or type 1 diabetic. Added to the requirement for documentation of effort to cease nicotine use that this does not include nicotine replacement therapy. Added to section II that all indications not noted in section I are not medically necessary. Added Page 7 of 10 Revision Date 04/20 Approval Date 04/20 05/20 06/20

   CLINICAL POLICY Skin Substitutes Reviews, Revisions, and Approvals CPT codes: 15271-15278; updated list of HCPCS codes of current products available, although not inclusive or guarantee of coverage. References reviewed and updated. All instances of “member” changed to “member/enrollee.” HCPCS codes removed as they are not included in Medicare Article A56696: Q4150, Q4183, Q4190, Q4208-Q4226. Q4210, Q4217, Q4219, and Q4220 removed. New codes added (from Article A56696): Q4176, Q4237, Q4238, and Q4239. Annual review completed. References reviewed and updated. Changed “Review Date” in the header to “Date of Last Revision” and “Date” in the revision log header to “Revision Date.” Added “type 2 diabetes” to I.A. Reworded some extraneous language with no clinical significance. Added to I.F.2. “unless Integra® is used per FDA guidelines”. Removed I.J.3. “Concurrent treatment with hyperbaric oxygen therapy”. Background section updated with no additional impact to criteria. Added the following HCPCS codes: A2001-A2010, Q4199, Q4201, Q4232 and Q4254. Removed Q4119, Q4174. Added reference CMS A56696. Specialist reviewed. Revision Date Approval Date 04/21 04/21 04/22 04/22 Updated description for code Q4128. 10/22