Study Of The Effect Of Fragmin In The Treatment Of Neuroischaemic Foot Ulcers In Diabetic Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of the study isto see the effect of Fragmin on the healing of diabetic foot ulcers by determining the number of subjects with ≥50% reduction in ulcer surface area including intact skin healing.

Official Title
-----------------
A 6 Month, Prospective, Randomized, Double Blind, Placebo-Controlled, Parallel Group, Multiple Center Trial To Evaluate The Efficacy And Safety Of Fragmin In The Treatment Of Chronic Neuroischaemic Foot Ulcers In Diabetic Patients

Conditions
-----------------
Diabetic Foot Ulcer

Intervention / Treatment
-----------------
* Drug: Fragmin/ Dalteparin Sodium
* Drug: Placebo for Fragmin/ Dalteparin Sodium


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects 18 years of age with type 1 or type 2 diabetes. Subjects with peripheral occlusive arterial disease (PAOD) and a neuropathy disability score (NDS) of >3 Exclusion Criteria: Subjects who have undergone vascular reconstruction or angioplasty less than 1 month prior to randomization. Subjects with an ulcer grading of 0 or 3 and staging of A, B or D according to the University of Texas wound classification system. Subjects with a known bleeding disorder or evidence of active bleeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Active study treatment | Drug: Fragmin/ Dalteparin Sodium<br>* Pre-filled syringes containing a single dose of 5000 IU Fragmin/ Dalteparin Sodium.<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo for Fragmin/ Dalteparin Sodium<br>* Pre-filled syringes containing a single dose of placebo for 5000 IU Fragmin/ Dalteparin Sodium.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Greater Than or Equal to 50 Percent Reduction in Ulcer Surface Area Including Intact Skin Healing | University of Texas (UT) system assesses ulcer depth, wound infection and clinical signs of lower-extremity ischemia. UT Wound Classification (1C/2C) was based on grade (0= healed site to 3= penetrating wound to bone or joint) and stage (A= clean wounds to D= ischaemic infected wounds) of wounds. Participants were evaluated at 4 stratums: Stratum 1: Toe pressure>30 mm of mercury (mmHg) and UT grade and stage 1C. Stratum 2: Toe pressure<=30 mmHg and UT grade and stage 1C. Stratum 3: Toe pressure>30 mmHg and UT grade and stage 2C. Stratum 4: Toe pressure<=30 mmHg and UT grade and stage 2C. | Week 24 [end of treatment (EOT)] or early termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Intact Skin Healing | Intact skin healing was defined as 100 percent reduction in ulcer surface area with full epithelialisation. UT system assesses ulcer depth, wound infection and clinical signs of lower-extremity ischemia. Participants were evaluated at 4 stratums: Stratum 1: Toe pressure>30 mm of mercury (mmHg) and UT grade and stage 1C. Stratum 2: Toe pressure<=30 mmHg and UT grade and stage 1C. Stratum 3: Toe pressure>30 mmHg and UT grade and stage 2C. Stratum 4: Toe pressure<=30 mmHg and UT grade and stage 2C. | Week 24 (EOT) or early termination | 
| Number of Participants Who Underwent Any Amputation | Any amputation included both major and minor amputations. A major amputation was defined as above the ankle and was reported as below-the-knee and above-the-knee amputations. A minor amputation was defined as below the ankle amputation. | Week 24 (EOT) or early termination | 
| Number of Participants Who Underwent Major and Minor Amputation | A major amputation was defined as above the ankle and was reported as below-the-knee and above-the-knee amputations. A minor amputation was defined as below the ankle amputation. | Week 24 (EOT) or early termination | 
| Number of Participants With Greater Than or Equal to 50 Percent Reduction in Ulcer Surface Area Excluding Intact Skin Healing | University of Texas (UT) system assesses ulcer depth, wound infection and clinical signs of lower-extremity ischemia. UT Wound Classification (1C/2C) was based on grade (0= healed site to 3= penetrating wound to bone or joint) and stage (A= clean wounds to D= ischaemic infected wounds) of wounds. Participants were evaluated at 4 stratums: Stratum 1: Toe pressure>30 mm of mercury (mmHg) and UT grade and stage 1C. Stratum 2: Toe pressure<=30 mmHg and UT grade and stage 1C. Stratum 3: Toe pressure>30 mmHg and UT grade and stage 2C. Stratum 4: Toe pressure<=30 mmHg and UT grade and stage 2C. | Week 24 (EOT) or early termination | 
| Number of Participants Who Died |  | Week 24 (EOT) or early termination | 
| Number of Participants With Major Cardiovascular Disease Events (MCVE) | Major cardiovascular events were defined as death due to vascular cause; non-fatal myocardial infarction (MI) excluding procedure related to MI; coronary revascularization procedures not related to MIs; hospitalization for unstable angina or non-fatal stroke. | Week 24 (EOT) or early termination | 
| Time to Intact Skin Healing | Median time taken to achieve intact skin healing which was defined as 100 percent reduction in ulcer surface area with full epithelialisation. | Week 24 (EOT) or early termination | 
| Median Time to First Amputation |  | Week 24 (EOT) or early termination | 
| Euro Quality of Life-5 Dimensions (EQ-5D)- Utility Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. It assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. | Baseline and Week 24 (EOT or early termination) | 
| Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. | Baseline and Week 24 (EOT or early termination) | 
| 36-Item Short-Form Health Survey (SF-36) Score | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). | Baseline and Week 24 (EOT or early termination) | 
| 11-point Likert Pain Scale | The 11 point Likert pain scale which used a 0 (no pain) to 10 (worst possible pain) point rating system was used to assess participant's pain score. No distinction was made between neuropathy and inflammatory (nociceptive) pain. | Baseline and Week 24 (EOT or early termination) | 
| Transcutaneous Local Tissue Oxygenation (pO2) | Transcutaneous pO2 was assessed at the dorsum of the foot in the first intermetatarsal space using an appropriately calibrated instrument. The skin oxygen partial pressure was determined by measuring the oxygen reduction current by means of a measuring cell. | Baseline and Week 24 (EOT or early termination) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetic Foot Ulcers Neuroischaemic