Comparison of Resin Salve and Octenidine in Patients With Neuropathic Diabetic Foot Ulcers
Condition: Diabetes Mellitus; Diabetes Complications; Diabetic Neuropathies; Wound Infection
MeSH terms: Wound Infection; Diabetic Neuropathies; Diabetic Foot; Foot Ulcer; Diabetes Mellitus; Diabetes Complications
Study type: Interventional

Summary: 
      Prevalence of diabetic foot ulcers are reported to be 15% in patients who suffer from
      diabetes and ulcerations are present in 84% of all diabetes-related amputations. Peripheral
      neuropathy leading to unperceived trauma seems to be the major cause of diabetic foot ulcers
      with 45-60% of ulcers to be considered merely neuropathic and 45% of mixed, neuropathic and
      ischemic etiology. Ulceration of lower limb is one of the most common complications related
      with diabetes and one of the major causes for hospitalization of diabetic patients. The most
      significant contributors to diabetic lower limb ulceration are neuropathy, deformity,
      uncontrolled elevated plantar pressure, poor glycemic status, peripheral vascular disease,
      male gender and duration of diabetes. Treatment of lower limb ulcers imposes an enormous
      burden on health care resources worldwide, and at least 33% of all expenses are spent to
      treat diabetic ulcers manifested as a complication of diabetes.

      Although at least 170 topical wound care products are available, evidence of the superiority
      of one over another is tenuous, well-designed randomized, controlled trials are rare, and the
      number of case-control or observational studies is limited. In recent years, salve prepared
      from Norway spruce (Picea abies) resin has successfully been used in medical context to treat
      both acute and chronic wounds and ulcers of various origins. The objective of this
      prospective, randomized and controlled clinical trial is to investigate healing rate and
      healing time of neuropathic diabetic foot ulcer in patients, who are suffering from infected
      fore- or mid-foot ulceration (PEDIS-classification ≥ Grade II; 19) originated from Type I or
      II diabetes, and in patients whose diabetic ulcerations are candidates for topical treatment
      with resin (Study treatment) or octenidine (Control treatment). In addition, factors
      contributing with delayed healing of ulceration, antimicrobial properties, safety and
      cost-effectiveness of the resin salve treatment and control treatment will be analyzed.
    

Detailed description: 
      PRIMARY OBJECTIVES

      Primary objectives are:

        -  to scrutinize complete healing of neuropathic diabetic foot ulceration over time.

        -  to analyze successful eradication rate of pathogenic bacteria from the ulcers within the
           study period as documented by negative swab culture.

        -  to analyze the rate of ulcers with 50% decrease in ulcer size and disappearing of
           clinical signs of infection over time.

      SECONDARY OBJECTIVES

      Secondary objectives are:

        -  to assess potential contributors to delayed ulcer healing.

        -  to study the safety and compliance related with the treatment methods.

        -  to estimate the overall costs of the ulcer treatment with the resin salve treatment or
           octenidine treatment.

      INCLUSION AND EXCLUSION CRITERIA

      Inclusion criteria are:

        -  an adult patient (18-80 years) with infected neuropathic foot ulceration due to type I
           or II diabetes.

        -  PEDIS-classification ≥ Grade II.

      Exclusion criteria are:

        -  a patient whose life expectancy is less than 6 months.

        -  an ulceration of ischemic or neuroischemic origin.

        -  presence of systemic inflammatory response signs.

        -  heel ulceration.

        -  presence of osteomyelitis.

        -  pregnancy.

        -  known hypersensitivity to any of the ingredient including in the study or control
           treatment products. - a patient who is unable to give informed consent.

        -  a patient who has an advanced malignant disease.

      METHODS Patient selection Altogether 40 adult patients (18 - 80 years) suffering from
      infected neuropathic fore- or mid-foot ulceration originated from type I or II diabetes
      (PEDIS-classification ≥ Grade II) are randomly allocated into two groups (n = 20 patients /
      group) to receive either topical resin salve treatment or topical octenidine treatment for an
      appropriate diabetic ulceration. The patients who are recruited to the current study, are
      selected by the physicians, who are specialized in the treatment of diabetes and its
      complications. Treatment is commenced and followed-up at the outpatient clinic of the
      Diabetic Foot Clinic Regional Diabetic Centre, Department of Hypertension and Diabetology,
      Gdansk, Poland. Informed consent will be obtained from all patients.

      FOLLOW-UP Demographics, clinically relevant medical, and follow-up data is gathered on the
      Clinical Report Form (CRF) by the responsible physicians for every patient at the beginning
      of the study, and within the every visit at the Diabetic Foot Clinic of the Regional Diabetic
      Centre until the study ends at six months later, at last. Thus, all recruited patients visit
      at the Diabetic Foot Clinic: 1. in the beginning of the study, and at 1, 2, 3, and 4 week
      time-points thereafter. After that, consecutive visit for every 3 to 4 weeks are arranged
      until the ends after the 6 months from the initiation. If the patient's clinical situation
      requires more frequent visits at the Diabetic Foot Clinic, those are arranged on the basis of
      the decision of research physician.

      If the ulcer healing takes less than 6 months, the last follow-up information on the CRF is
      filled when the ulcer is considered being fully healed (primary objective is achieved). If
      the ulcer is not fully healed in 6 months, the treatment is considered unsuccessful, and
      follow-up is discontinued (primary objective is not achieved). Photographs are taken within
      every control visit at the outpatient department. Any notable improvement, deterioration, or
      any factor that might contribute with the ulcer healing during the follow-up, e.g. mechanical
      / surgical ulcer revision, cleansing, or antibiotic treatment will be registered on the CRF:
      Thus, CRF includes the details of:

        -  size of the ulcer [width (mm) x length (mm) x depth (mm)].

        -  signs of infection.

        -  swab culture.

        -  plain x-ray.

        -  erythrocyte sedimentation rate (ESR).

        -  C-reactive protein (CRP).

        -  full blood count.

        -  photographs with an appropriate measure.

        -  use of antibiotics.

        -  rate of dressing changes.

        -  potential side-effects (i.e. signs of hypersensitivity or allergic reaction).

        -  the use of off-loading shoe, and any specific notes or observations during the treatment
           period.

      SAFETY ISSUES Hypersensitivity or allergy for resin or control treatment is taken into
      account, and if any symptoms of allergic reactions i.e. contact dermatitis appear, the study
      is discontinued for this particular patient.
    

Intervention name(s): Resin salve treatment; Octenidine treatment
Intervention type(s): Device; Device
Intervention description(s): Resin is collected in the municipality of Kolari, Finland, from the trunks of full-grown Norway spruce (Picea acies) trees. Bark and other impurities are removed mechanically. The resin is then liquefied and purified by filtering. Resin salve is composed of a 10% (w/w) mixture of purified spruce resin in a standardized salve base. None of the components of the salve base have antibacterial properties. Resin salve is produced from the pure resin to the final product in accordance with the Good Manufacturing Standards (GMP) and it holds the European CE mark (Abilar 10% Resin Salve, Repolar Ltd., Espoo, Finland, CE 0537).; Octenidine dihydrochloride is a cationic surfactant and bis-(dihydropyridinyl)-decane derivative, used in concentrations of 0.1-2.0%. It is similar in its action to the quaternary ammonium compounds, but is of somewhat broader spectrum of activity. Octenidine is currently increasingly used in continental Europe as a substitute for quats or chlorhexidine (with respect to its slow action and concerns about the carcinogenic impurity 4-chloroaniline) in water- or alcohol-based skin, mucosa and wound antiseptics. In aqueous formulations, it is often potentiated with addition of 2-phenoxyethanol.
Other intervention name(s): Abilar 10% Resin Salve; Octenisept
Intervention MeSH terms: Octenidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes complications; Diabetic foot; Foot ulcer; Wound healing; Wound infection