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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Drug: Fragmin/ Dalteparin Sodium; Drug: Placebo for Fragmin/ Dalteparin Sodium

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Klagenfurt, Austria, A-9020
    • Pfizer Investigational Site
  • Wien, Austria, A-1090
    • Pfizer Investigational Site
  • Wien, Austria, A-1030
    • Pfizer Investigational Site
• Belgium
  • Ransart, Belgium, 6043
    • Pfizer Investigational Site
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Pfizer Investigational Site
• Czechia
  • Praha 4, Czechia, 140 21
    • Pfizer Investigational Site
  • Praha 5, Czechia, 150 06
    • Pfizer Investigational Site
  • Zlin, Czechia, 760 01
    • Pfizer Investigational Site
• Denmark
  • Aalborg, Denmark, 9100
    • Pfizer Investigational Site
  • Aarhus C, Denmark, 8000
    • Pfizer Investigational Site
  • Hvidovre, Denmark, 2650
    • Pfizer Investigational Site
  • Koebenhavn NV, Denmark, 2400
    • Pfizer Investigational Site
  • Odense C, Denmark, 5000
    • Pfizer Investigational Site
  • Soenderborg, Denmark, 6400
    • Pfizer Investigational Site
• Finland
  • Tampere, Finland, 33520
    • Pfizer Investigational Site
• Germany
  • Karlsbad, Germany, 76307
    • Pfizer Investigational Site
• Greece
  • Athens, Greece, 11527
    • Pfizer Investigational Site
  • Athens, Greece, 106 76
    • Pfizer Investigational Site
  • Melissia/Athens, Greece, 15127
    • Pfizer Investigational Site
  • Thessaloniki, Greece, 56429
    • Pfizer Investigational Site
• Italy
  • Firenze, Italy, 50139
    • Pfizer Investigational Site
  • Pisa, Italy, 56124
    • Pfizer Investigational Site
  • Roma, Italy, 00133
    • Pfizer Investigational Site
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Pfizer Investigational Site
• Lithuania
  • Kaunas, Lithuania, 49476
    • Pfizer Investigational Site
  • Vilnius, Lithuania, 10207
    • Pfizer Investigational Site
  • Vilnius, Lithuania, 01102
    • Pfizer Investigational Site
• Norway
  • Tonsberg, Norway, 3103
    • Pfizer Investigational Site
• Poland
  • Gdansk, Poland, 80-952
    • Pfizer Investigational Site
  • Lodz, Poland, 90-153
    • Pfizer Investigational Site
  • Pulawy, Poland, 24-100
    • Pfizer Investigational Site
  • Warszawa, Poland, 02-097
    • Pfizer Investigational Site
  • Wroclaw, Poland, 51-124
    • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 123423
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 127486
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 119034
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 109240
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 115998
    • Pfizer Investigational Site
  • Saint-Petersburg, Russian Federation, 194156
    • Pfizer Investigational Site
• Spain
  • Girona, Spain, 17007
    • Pfizer Investigational Site
  • Madrid, Spain, 28040
    • Pfizer Investigational Site
  • Madrid
    • Getafe, Madrid, Spain, 28905
      • Pfizer Investigational Site
• Sweden
  • Karlstad, Sweden, 651 85
    • Pfizer Investigational Site
  • Malmö, Sweden, 205 02
    • Pfizer Investigational Site
  • Stockholm, Sweden, 182 88
    • Pfizer Investigational Site
  • Stockholm, Sweden, 17176
    • Pfizer Investigational Site
  • Stockholm, Sweden, 141 86
    • Pfizer Investigational Site
  • Stockholm, Sweden, 11883
    • Pfizer Investigational Site
  • Stockholm, Sweden, 18288
    • Pfizer Investigational Site
• Ukraine
  • Kharkiv, Ukraine, 61002
    • Pfizer Investigational Site
  • Kyiv, Ukraine, 02091
    • Pfizer Investigational Site
  • Lviv, Ukraine, 79010
    • Pfizer Investigational Site
  • Odessa, Ukraine, 65009
    • Pfizer Investigational Site
• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
    • Pfizer Investigational Site
  • Birmingham, United Kingdom, B9 5SS
    • Pfizer Investigational Site
  • Colchester, United Kingdom, CO4 5JL
    • Pfizer Investigational Site
  • Coventry, United Kingdom, CV2 2DX
    • Pfizer Investigational Site
  • Dundee, United Kingdom, DD1 9SY
    • Pfizer Investigational Site
  • Ipswich, United Kingdom, IP4 5PD
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M13 9WL
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M13 0JE
    • Pfizer Investigational Site
  • Peterborough, United Kingdom, PE3 9GZ
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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)

Other 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 more than or equal to 20 gram (g)/litre (L) (2 g/ decilitre [dL]), clinically overt bleeding leading to transfusion of more 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.	Week 24 (EOT) or early termination
Number of Major and Minor Hemorrhages	Major hemorrhages: defined as fatal bleeding, clinically overt bleeding causing a fall in hemoglobin more than or equal to 20 gram (g)/litre (L) (2 g/ decilitre [dL]), clinically overt bleeding leading to transfusion of more 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.	Week 24 (EOT) or early termination
Number of Clinically Relevant Minor Hemorrhages and Trivial 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. Trivial bleeding was defined as all minor bleeding that did not meet the definition of clinically relevant minor bleeding.	Week 24 (EOT) or early termination

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: April 16, 2008
• First Submitted That Met QC Criteria: April 17, 2008
• First Posted (Estimate): April 21, 2008

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: November 29, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Diabetic Foot Ulcers Neuroischaemic
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: A6301083