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

• Register: EUCTR
• Last refreshed on: 10 July 2012
• Main ID: EUCTR2007-005784-10-GB
• Date of registration: 26/11/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public 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
• Scientific 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
• Date of first enrolment: 11/01/2008
• Target sample size: 645
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005784-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Lithuania, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects =18 years of age.
2. Subjects with type 1 or type 2 diabetes.
3. Subjects with peripheral occlusive arterial disease (PAOD) who have the following:
• Thorough clinical assessment by the treating clinical team to exclude all other
available PAOD treatment options (ie, revascularization etc)
• Toe/arm blood pressure index =0.8.
4. Subjects must have a neuropathy disability score (NDS) of =3.
5. Subjects with chronic foot ulcers (defined as an ulcer for >2 months) and an ulcer area between 25-2500 mm2. All ulcers must have an ulcer staging of 1C and 2C according to the University of Texas wound classification system.
6. Subjects must be on a minimum of 75 mg of aspirin (or equivalent dose of calcium carbasalate or other acetylsalicylic acids) daily for at least 4 weeks prior to randomization and the aspirin/ calcium carbasalate or other acetylsalicylic acid therapy must be continued for the entire duration of the study.
7. Subjects with ulcer infections at screening as assessed by the presence of clinical signs of infection must be treated with appropriate antibiotics (in accordance to any available bacterial culture and sensitivity pattern results) prior to randomization.
8. Subjects must be willing to comply with the protocol, scheduled visits, laboratory tests and medication regimen.
9. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects who have undergone vascular reconstruction or angioplasty less than 1 month prior to randomization.
2. Subjects with an ulcer grading of 0 or 3 or staging of A, B or D according to the University of Texas wound classification system.
3. Subjects with a known bleeding disorder or evidence of active bleeding.
4. Subjects who are on dialysis.
5. Subjects with hepatic dysfunction defined as an International normalisatized Ration (INR) >2.0.
6. Subjects with proliferative diabetic retinopathy that in the investigators opinion will
result in an increased risk of hemorrhage if treated with dalteparin.
7. Subjects who have undergone a major organ transplant and/or treatment with
immunosuppressive agents.
8. Subjects who have participated in a study of an investigational drug or device within four weeks of study entry.
9. Subjects with malignant ulcers, all subjects with clinically suspicious ulcers will require a biopsy to exclude a malignancy prior to enrollment.
10. Female subjects who are pregnant, lactating, or planning a pregnancy during the course of the study, or who are of child bearing potential and not using an acceptable method of birth control. Female subjects should continue contraceptive methods during the study and for at least 30 days after receiving their last treatment.
11. Subjects treated with anticoagulants or anti-platelet therapy other than aspirin/ or calcium carbasalate) such as warfarin, clopidogrel or low molecular weight heparins.
12. Abuse of alcohol and/or any other drug in the opinion of the investigator.
13. Subjects with contraindications to dalteparin administration, which include:
• Known hypersensitivity to the active ingredient in dalteparin or to any of the
excipients of this product.
• History of confirmed or suspected immunologically mediated heparin induced
thrombocytopenia.
• Severe hypertension.
• Acute gastroduodenal ulcer, cerebral hemorrhage or known hemorrhagic diathesis.
• Subacute endocarditis.
• Injuries to and operations on the central nervous system, eyes and ears (within the last month).
14. Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetic Foot Ulcer
MedDRA version: 9.1 Level: LLT Classification code 10012664 Term: Diabetic foot ulcer

Intervention(s)

Trade Name: Fragmin
Product Code: PNU-180524E
Pharmaceutical Form: Injection*
INN or Proposed INN: Dalteparin sodium
CAS Number: 9041-08-1
Current Sponsor code: PNU-180524E
Other descriptive name: Fragmin
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 5000 IU/0.2-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: Evaluate the effect of dalteparin compared to placebo on the healing of chronic neuroischaemic foot ulcers in diabetic patients with peripheral arterial occlusive disease (PAOD) and peripheral neuropathy, as determined by the number of patients who have =50% reduction in ulcer surface area including intact skin healing after a maximum of 6 months of treatment.

Primary end point(s): The primary endpoint will be the following:

• Number of subjects with =50% reduction in ulcer surface area including intact skin
healing.

Secondary Objective: The key secondary objectives are to evaluate the number of diabetic subjects with chronic neuroischaemic foot ulcers who had intact skin healing. The number of subjects who have required an amputation within the 6 month treatment period will also be investigated. The safety and tolerability of dalteparin compared to placebo in treatment of diabetic patients with neuroischaemic foot ulcers will also be evaluated.

Secondary ID(s)

2007-005784-10-SE

A6301083