Status and phase
Conditions
Treatments
About
Foot ulcers represent a significant common complication in patients with diabetes. Wound healing is a challenge. Some wounds do not respond to the best practices in wound care. Considerable effort has been directed at therapies to improve the rate of healing.
There are a variety of growth factors which have been used to stimulate wound healing. Human platelets are an autologous source of growth factors which probably can stimulate healing. Autologous platelet gel (APG) is prepared by centrifugation of autologous human whole blood. APG is rich in platelet growth factors. This study will investigate the potential improvement in wound healing with this material in diabetic foot ulcers.
This study will compare the use of autologous platelet gel ( study group) and standard care ( control group) in the treatment of diabetic plantar forefoot ulcers. This study will also compare the cost and quality of life in the two groups.
Objectives of the study:
Full description
Study Design This will be a single center, randomized, controlled, prospective study comparing the use of autologous platelet gel (study group) and traditional moist dressing (control group) in the treatment of plantar forefoot ulcers.
Specific Aims Primary - Facilitation of healing of diabetic foot ulcers Secondary - Reduction in amputations and average total cost of care. Determine the impact of diabetic ulcers on patients' quality of life Research Background Foot ulcers represent a significant common complication in patients with diabetes. It is estimated that twenty percent of all patients with diabetes develop a foot ulcer which may subsequently lead to below knee amputation. 85 % of them preceded by non-healing foot ulcers.
Health care costs associated with diabetic foot wound management are staggering. Armstrong et al (1998) reported that wound care for foot ulcer patients over a two year period had mean cost of $27,000.00 U.S. In Toronto, the average cost of below knee amputations, including hospitalization and rehabilitation, is $40,000.00.
Wound healing in the context of diabetes is a challenge for both the health care provider and the patient. In a systematic review conducted by Margolis et al (1999), wound healing outcomes using best practices have yielded only 24% at 12 weeks, 31% in 20 weeks.
Falanga & Sabolinski (2001) identified that initial wound size reduction of 0.1 cm/week is highly predictive of wound closure whereas initial healing rates 0.06 cm or less predict non-healing. Similarly, 51% percent reduction in 4 weeks was found to be a good predictor of achieving wound closure (Margolis et al, 1999). Some wounds do not respond and considerable effort has been directed at therapies to improve the rate of healing in this situation.
A variety of growth factors which have been used to stimulate wound healing. Human platelets are an autologous source which probably can stimulate healing. Autologous platelet gel (APG) is a material presently utilized as a tissue adhesive. It is derived from platelet rich plasma (PRP) that was first developed in the early 1990's to primarily address acute surgical hemostatic and wound healing problems.
APG is prepared by centrifugation of autologous human whole blood, which initially separates it into three components: packed red cells, platelet poor plasma, and platelet rich plasma (PRP). PRP has two to eight times the normal concentration of platelets in human blood. The key element that differentiates APG from traditional fibrin glue is the presence of concentrated platelets rich in platelet growth factors. These important elements of the blood, in an increased concentration are potentially helpful in improving the rate of wound healing. This study will investigate the potential improvement in wound healing with APG in diabetic foot ulcers.
Rationale for the Research
Inclusion Criteria
>18 years of age
Type I or Type II Diabetes
Plantar forefoot ulcer(s) beneath metatarsal head or toe ulcer which has been present for at least 4 weeks, and has received best practice care
Evidence of adequate arterial perfusion: Toe plethysmography reading of ≥ 45 mmHg or Transcutaneous oxygen measurement of ≥ 30mmHg
Patient is appropriately offloaded (contact cast, pneumatic walking cast)
Infection and/or osteomyelitis have been ruled out or are being treated
Platelet count greater than150,000/mm3
Orthopedic assessment has been completed to rule out mechanical source of ulceration
Patients with following skeletal deformities could be included -
Patients taking clopidogrel (Plavix) and aspirin could be included in the study. Patients taking aspirin for non medical reason will be asked to discontinue the medicine one week before the start of treatment.
Exclusion Criteria
TcPO2 <30 mmHg and/or toe plethysmography readings of less than 45 mmHg
Limb ischemia requiring re-vascularization or impending amputation
Untreated wound infection or osteomyelitis
Bleeding disorders, hemophilia, sickle cell disease, thrombocytopenia, and leukemia or blood dyscrasias
Anemia with hemoglobin level less than 100 g/L will be included as exclusion criteria.
Patient is taking immunosuppressive agents (e.g. corticosteroids, chemotherapeutic agents, transplant medications)
Current treatment for malignancy or neoplastic disease or collagen vascular disease
Patients taking anticoagulants like heparin or coumadin or others which may hinder in clot (thrombin) formation
Patient has a highly communicable disease or diseases that may limit follow - up (e.g. immuno-compromised conditions, hepatitis, active tuberculosis)
Ulcers resulting from electrical, chemical, radiation burns
Serum creatinine level >110 umol/L
HbA1c > 9%
Currently participating in another investigation study
Ulcer with exposed bone or tendon Withdrawal Criteria
The patient may be withdrawn from the study at the discretion of the investigator if judged noncompliant with study procedures or worsening patient condition 2. Detection of osteomyelitis that is not treatable by debridement and antibiotics at the discretion of the investigator 3. Development of progressive wound necrosis Experimental Methods For study purposes, diabetic foot ulcer will be a wound on the plantar aspect of the foot which has not responded to at least 4 weeks of best practice care. Complete wound closure will be defined as skin closure (100% re-epithelization) without drainage or dressing requirements.
Patients seeking treatment for diabetic foot ulcers that meet the entry criteria will be considered for the study. Patients will be randomized to either the STUDY or the CONTROL group with a 1:1 control to study ratio.
STUDY Group Patients will have APG (autologous platelet gel) applied to the wound in accordance with institutional treatment protocols and manufacturer's guidelines. Dressing changes will occur at least three times a week.
Method of preparing and application of autologous platelet gel is as follows -
CONTROL Group
Weekly standard therapy alone as follows:
Treatment Phase of the Study: Treatment in both groups will continue until the wound is successfully closed.
At 12 weeks (3 months) wounds from both control and treatment groups will be evaluated. If the wound does not show any signs of improvement (wound closure by 50% at 3 months) the wound will be considered as a treatment failure and it will be treated with alternate dressing according to hospital standard of care. These wounds will be followed every month till they close.
6-Month and 12 month follow-up: For patients who achieved wound closure at 12 weeks, or later the wound site will undergo an examination for recurrence.
No patient will remain in the study for longer than 12 months (total study duration).
Clinical Assessments A. Wound Debridement All wounds under study will be surgically debrided The wound may be debrided by autolysis or sharp wound debridement as tolerated.
B. Laboratory Testing Up to seven days prior to the initiation of protocol treatment, blood samples will be taken to determine serum pre-albumin, albumin and creatinine levels. If the pre-albumin is <16 mg/dl (<160 mg/L) or the albumin level is <3 g/dl (<30 g/L), nutritional supplementation will be started. The tests will be repeated at 12 weeks or at the time of wound closure which ever comes first. Determination of HbA1c will be performed up to 30 days prior to initiation of protocol treatment, and at 12 weeks or at the time of wound closure which ever comes first.
Bacterial culture will be done at Day 0. Additional cultures may be obtained as clinically indicated.
C. Wound Examination Ulcers will be examined at Days 0, 7 (1 wk), 14 (2wk), 28 (4wk) , 56 (8wk), 84 (12wk), 6 and 12 month follow up visits.
The ulcer will be classified using the University of Texas Scale Diabetic Foot ulcer Classification System.
The ulcer will be evaluated using following criteria:
E. Documentation of Dressings - The number and type of dressings used will be documented by the health care professional taking care of the patient.
F. Cost - Frequency of dressing changes and estimates of material cost and nursing time will be documented Data Collection/Study Visit Procedures Visit 1 (Day -7 to Day 0) Screening Patients will be screened and data will be collected for demographic details, relevant medical and surgical history, lab values, results of vascular studies and Plastic and / or Orthopedic Surgeons' consultations Visit 2 (Day 0) Randomization/Treatment It will take place within 7 days after Visit 1. Patients will be randomized. Wounds will be assessed, photographed and measured and data will be collected.
Visit 3, 4, 5, 6, and 7 (week 1 (05 days), week 2, 4, 8 and 12) Wounds will be assessed, photographed and measured and data will be collected. Number of dressing changes per week, materials used and the occupation of person performing the dressing change will be documented. The time to definitive wound closure will be recorded. Pre-albumin, albumin creatinine and HbA1c will be tested at week 12. Ulcer recurrence and its cause will be documented.
Visit 8 and 9 (6 Month and12 Month Follow-up) Assessment of Recurrence These visits will occur at 6 months and 12 months for both treatment groups. The wound will be examined for recurrence or determination of wound status. Information about patient's quality of life using Cardiff Wound Impact questionnaire, 6 months after healing of the ulcer will be collected.
Adverse Events Through out the study period adverse events, also termed "study events" and "adverse experiences" and serious adverse events will be recorded.
Statistical Analysis Endpoints will include: time to 25% percent closure at 6 weeks, time to 50% closure at 12 weeks and time to definitive closure Analyses will include - time to 50-percent-closure, time to definitive closure, percentage of wounds closed at study calendar time points/visits, number of dressing changes and impact of diabetic foot ulcer on the quality of life Survival analysis, ANOVA/ANCOVA, and non-parametric analysis will be used. A repetitive measurement analysis will also be applied. Ordinal Categorical Analysis will be performed on data from Cardiff Wound Impact Schedule.
Sex
Ages
Volunteers
Inclusion criteria
Patient is greater than 18 years of age
Patient has Type I or Type II Diabetes
Patient must be able to understand English (self or translator) and give written, informed consent
Patient has a plantar forefoot ulcer(s) beneath metatarsal head or toe ulcer which has been present for at least 4 weeks, and has received best practice care
Evidence of adequate arterial perfusion: Toe plethysmography reading of
Patient is appropriately offloaded (contact cast, pneumatic walking cast)
Infection and/or osteomyelitis have been ruled out or are being treated
Patients must have a platelet count greater than150,000/mm3
Orthopedic assessment has been completed to rule out mechanical source of ulceration
Patients with following skeletal deformities could be included -
Patients taking clopidogrel (Plavix) and aspirin could be included in the study. Patients taking aspirin for non medical reason will be asked to discontinue the medicine one week before the start of treatment.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal