The Effect Of Fragmin In The Treatment Of Neuroischaemic Foot Ulcers In Diabetic Patients (A6301086)

Study Overview
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Brief Summary
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The primary objective of this 6 month open-label extension trial is to evaluate long-term safety and tolerability of dalteparin in treatment of chronic neuroischaemic foot ulcers in diabetic patients with peripheral arterial occlusive disease (PAOD) and peripheral neuropathy.

Official Title
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A 6 Month, Prospective, Open-Label Multiple Center Extension Trial To Evaluate The Long Term Safety And Sustained Efficacy Of Fragmin In The Treatment Of Chronic Foot Ulcers In Diabetic Patients With Peripheral Arterial Occlusive Disease

Conditions
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Diabetic Foot Ulcer

Intervention / Treatment
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* Drug: Fragmin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have completed the 6 month study duration in the A6301083 study. Subjects must have a positive ulcer treatment response, defined as a reduction in the study ulcer area size (ie, ulcer area reduction >0%) at Visit 8 (EOT Visit) from baseline in the A6301083 study. All ulcers must have an ulcer staging of 1C, 2C, 1D or 2D according to the University of Texas wound classification system Exclusion Criteria: Subjects who have the following: Intact skin healing (defined as 100% reduction in ulcer surface area with full epithelialisation at or prior to the EOT visit in the A6301083 study). A study ulcer area at Visit 8 (EOT visit) which is greater or equal to the baseline ulcer area (ie, ulcer area increase ≥0%) in the A6301083 study. Subjects with an ulcer grading of 0 or 3 or staging of A or B according to the University of Texas wound classification system. Subjects with a known bleeding disorder or evidence of active bleeding. Subjects who are on dialysis. Subjects who where found to be major protocol violators in A6301083 study. Subjects who did not complete the 6 month study period of the A6301083 study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Active study treatment | Drug: Fragmin<br>* Pre-filled syringes containing a single dose of 5000 IU Fragmin/ Dalteparin Sodium<br>* Other names: Dalteparin sodium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of All Hemorrhages | Major hemorrhages: defined as fatal bleeding, clinically overt bleeding causing a fall in hemoglobin greater than or equal to 20 gram (g)/litre (L) (2 g/ decilitre [dL]), clinically overt bleeding leading to transfusion of greater than or equal to 2 units of whole blood or red cells, or symptomatic bleeding in areas of special concern (intracranial, retroperitoneal, intraocular, intraspinal, pericardial, intramuscular with compartmental syndrome, or intraarticular). Minor hemorrhages: defined as bleeding that did not meet the definition of major bleeding. | Baseline to Week 24 (end of treatment [EOT]) or early termination (ET) | 
| Number of Major Hemorrhages | Major hemorrhages: defined as fatal bleeding, clinically overt bleeding causing a fall in hemoglobin greater than or equal to 20 g/L (2 g/dL), clinically overt bleeding leading to transfusion of greater than or equal to 2 units of whole blood or red cells, or symptomatic bleeding in areas of special concern (intracranial, retroperitoneal, intraocular, intraspinal, pericardial, intramuscular with compartmental syndrome, or intraarticular). | Baseline to Week 24 (EOT) or ET | 
| Number of Minor Hemorrhages | Minor hemorrhages: defined as bleeding that did not meet the definition of major bleeding. | Baseline to Week 24 (EOT) or ET | 
| Number of Clinically Relevant Minor Hemorrhages | Clinically relevant minor (non-major) bleeding was defined as any bleeding compromising hemodynamics, leading to hospitalization, subcutaneous haematoma more than 25 cm^2, intramuscular haematoma, epistaxis lasting for more than 5 minutes, spontaneous gingival bleeding, macroscopic hematuria and gastrointestinal hemorrhage (including at least 1 episode of melaena or hematemesis), rectal blood loss, hemoptysis, and any other bleeding with clinical consequences. | Baseline to Week 24 (EOT) or ET | 
| Number of Trivial Hemorrhages | Trivial bleeding was defined as all minor bleeding that did not meet the definition of clinically relevant minor bleeding. | Baseline to Week 24 (EOT) or ET | 

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. The ulcer area was measured in square millimetre (mm) by measuring the longest width and length of the ulcer after debridement. The area was calculated from an acetate tracing. Ulcers were also documented by standardized photographs. The largest ulcer was considered the study ulcer in participants with multiple ulcers. | Baseline through Week 24 (EOT) or ET | 
| Number of Participants With Improved Ulcer Healing | Improved ulcer healing was defined as greater than or equal to 50 percent reduction in ulcer surface area from baseline of the A6301083 study excluding intact skin healing. The ulcer area was measured in square mm by measuring the longest width and length of the ulcer after debridement. Ulcers were also documented by standardized photographs. | Baseline through Week 24 (EOT) or ET | 
| Number of Participants Who Underwent 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. | Baseline through Week 24 (EOT) or ET | 
| Time to Intact Skin Healing | Median time (in months) taken to achieve intact skin healing which was defined as 100 percent reduction in ulcer surface area with full epithelialisation. | Baseline through Week 24 (EOT) or ET | 
| Time to First Amputation |  | Baseline through Week 24 (EOT) or ET | 
| Number of Participants With Major Cardiovascular Disease Events (MCVE) | MCVE 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. | Baseline through Week 24 (EOT) or ET | 
| 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 ET | 
| 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 ET | 

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