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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00662831
• Collaborator: (none)
• Enrollment: 276
• Locations: 63
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Foot Ulcer	Drug: Fragmin/ Dalteparin Sodium; Drug: Placebo for Fragmin/ Dalteparin Sodium	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 276 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Greater Than or Equal to 50 Percent Reduction in Ulcer Surface Area Including Intact Skin Healing [Week 24 [end of treatment (EOT)] or early termination]

   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.

Secondary Outcome Measures

1. Number of Participants With Intact Skin Healing [Week 24 (EOT) or early termination]

   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.

2. Number of Participants Who Underwent Any Amputation [Week 24 (EOT) or early termination]

   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.

3. Number of Participants Who Underwent Major and Minor Amputation [Week 24 (EOT) or early termination]

   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.

4. Number of Participants With Greater Than or Equal to 50 Percent Reduction in Ulcer Surface Area Excluding Intact Skin Healing [Week 24 (EOT) or early termination]

   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.

5. Number of Participants Who Died [Week 24 (EOT) or early termination]

6. Number of Participants With Major Cardiovascular Disease Events (MCVE) [Week 24 (EOT) or early termination]

   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.

7. Time to Intact Skin Healing [Week 24 (EOT) or early termination]

   Median time taken to achieve intact skin healing which was defined as 100 percent reduction in ulcer surface area with full epithelialisation.

8. Median Time to First Amputation [Week 24 (EOT) or early termination]

9. Euro Quality of Life-5 Dimensions (EQ-5D)- Utility Score [Baseline and Week 24 (EOT or early termination)]

   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.

10. Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS) [Baseline and Week 24 (EOT or early termination)]

    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.

11. 36-Item Short-Form Health Survey (SF-36) Score [Baseline and Week 24 (EOT or early termination)]

    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).

12. 11-point Likert Pain Scale [Baseline and Week 24 (EOT or early termination)]

    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.

13. Transcutaneous Local Tissue Oxygenation (pO2) [Baseline and Week 24 (EOT or early termination)]

    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.

Other Outcome Measures

1. Number of All Hemorrhages [Week 24 (EOT) or early termination]

   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.

2. Number of Major and Minor Hemorrhages [Week 24 (EOT) or early termination]

   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.

3. Number of Clinically Relevant Minor Hemorrhages and Trivial Hemorrhages [Week 24 (EOT) or early termination]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Klagenfurt		Austria	A-9020
2	Pfizer Investigational Site	Wien		Austria	A-1030
3	Pfizer Investigational Site	Wien		Austria	A-1090
4	Pfizer Investigational Site	Ransart		Belgium	6043
5	Pfizer Investigational Site	Winnipeg	Manitoba	Canada	R3A 1R9
6	Pfizer Investigational Site	Montreal	Quebec	Canada	H1T 2M4
7	Pfizer Investigational Site	Praha 4		Czechia	140 21
8	Pfizer Investigational Site	Praha 5		Czechia	150 06
9	Pfizer Investigational Site	Zlin		Czechia	760 01
10	Pfizer Investigational Site	Aalborg		Denmark	9100
11	Pfizer Investigational Site	Aarhus C		Denmark	8000
12	Pfizer Investigational Site	Hvidovre		Denmark	2650
13	Pfizer Investigational Site	Koebenhavn NV		Denmark	2400
14	Pfizer Investigational Site	Odense C		Denmark	5000
15	Pfizer Investigational Site	Soenderborg		Denmark	6400
16	Pfizer Investigational Site	Tampere		Finland	33520
17	Pfizer Investigational Site	Karlsbad		Germany	76307
18	Pfizer Investigational Site	Athens		Greece	106 76
19	Pfizer Investigational Site	Athens		Greece	11527
20	Pfizer Investigational Site	Melissia/Athens		Greece	15127
21	Pfizer Investigational Site	Thessaloniki		Greece	56429
22	Pfizer Investigational Site	San Giovanni Rotondo	FG	Italy	71013
23	Pfizer Investigational Site	Firenze		Italy	50139
24	Pfizer Investigational Site	Pisa		Italy	56124
25	Pfizer Investigational Site	Roma		Italy	00133
26	Pfizer Investigational Site	Kaunas		Lithuania	49476
27	Pfizer Investigational Site	Vilnius		Lithuania	01102
28	Pfizer Investigational Site	Vilnius		Lithuania	10207
29	Pfizer Investigational Site	Tonsberg		Norway	3103
30	Pfizer Investigational Site	Gdansk		Poland	80-952
31	Pfizer Investigational Site	Lodz		Poland	90-153
32	Pfizer Investigational Site	Pulawy		Poland	24-100
33	Pfizer Investigational Site	Warszawa		Poland	02-097
34	Pfizer Investigational Site	Wroclaw		Poland	51-124
35	Pfizer Investigational Site	Moscow		Russian Federation	109240
36	Pfizer Investigational Site	Moscow		Russian Federation	115998
37	Pfizer Investigational Site	Moscow		Russian Federation	119034
38	Pfizer Investigational Site	Moscow		Russian Federation	123423
39	Pfizer Investigational Site	Moscow		Russian Federation	127486
40	Pfizer Investigational Site	Saint-Petersburg		Russian Federation	194156
41	Pfizer Investigational Site	Getafe	Madrid	Spain	28905
42	Pfizer Investigational Site	Girona		Spain	17007
43	Pfizer Investigational Site	Madrid		Spain	28040
44	Pfizer Investigational Site	Karlstad		Sweden	651 85
45	Pfizer Investigational Site	Malmö		Sweden	205 02
46	Pfizer Investigational Site	Stockholm		Sweden	11883
47	Pfizer Investigational Site	Stockholm		Sweden	141 86
48	Pfizer Investigational Site	Stockholm		Sweden	17176
49	Pfizer Investigational Site	Stockholm		Sweden	182 88
50	Pfizer Investigational Site	Stockholm		Sweden	18288
51	Pfizer Investigational Site	Kharkiv		Ukraine	61002
52	Pfizer Investigational Site	Kyiv		Ukraine	02091
53	Pfizer Investigational Site	Lviv		Ukraine	79010
54	Pfizer Investigational Site	Odessa		Ukraine	65009
55	Pfizer Investigational Site	Barnsley		United Kingdom	S75 2EP
56	Pfizer Investigational Site	Birmingham		United Kingdom	B9 5SS
57	Pfizer Investigational Site	Colchester		United Kingdom	CO4 5JL
58	Pfizer Investigational Site	Coventry		United Kingdom	CV2 2DX
59	Pfizer Investigational Site	Dundee		United Kingdom	DD1 9SY
60	Pfizer Investigational Site	Ipswich		United Kingdom	IP4 5PD
61	Pfizer Investigational Site	Manchester		United Kingdom	M13 0JE
62	Pfizer Investigational Site	Manchester		United Kingdom	M13 9WL
63	Pfizer Investigational Site	Peterborough		United Kingdom	PE3 9GZ

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00662831
• Other Study ID Numbers: A6301083
• First Posted: Apr 21, 2008
• Last Update Posted: Dec 19, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Pfizer: Diabetic Foot Ulcers Neuroischaemic
• Additional relevant MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer; Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight

Study Results

Participant Flow

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 milliliter [mL]) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Period Title: Overall Study
STARTED	184	92
COMPLETED	78	33
NOT COMPLETED	106	59

Baseline Characteristics

Arm/Group Title	Dalteparin	Placebo	Total
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.	Total of all reporting groups
Overall Participants	184	92	276
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.8 (10.3)	64.7 (10.9)	64.8 (10.5)
Sex: Female, Male (Count of Participants)
Female	63 34.2%	30 32.6%	93 33.7%
Male	121 65.8%	62 67.4%	183 66.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Greater Than or Equal to 50 Percent Reduction in Ulcer Surface Area Including Intact Skin Healing
Description	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.
Time Frame	Week 24 [end of treatment (EOT)] or early termination

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population included all participants who were randomized. Last observation carried forward (LOCF) method was used. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	92
Stratum 1 (n= 97, 49)	68 37%	31 33.7%
Stratum 2 (n= 39, 19)	23 12.5%	14 15.2%
Stratum 3 (n= 29, 14)	21 11.4%	10 10.9%
Stratum 4 (n= 19, 10)	9 4.9%	6 6.5%

2. Secondary Outcome

Title	Number of Participants With Intact Skin Healing
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized. LOCF method was used. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	92
Stratum 1 (n= 97, 49)	35 19%	16 17.4%
Stratum 2 (n= 39, 19)	15 8.2%	4 4.3%
Stratum 3 (n= 29, 14)	8 4.3%	4 4.3%
Stratum 4 (n= 19, 10)	1 0.5%	4 4.3%

3. Secondary Outcome

Title	Number of Participants Who Underwent Any Amputation
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	180	90
Number [participants]	8 4.3%	2 2.2%

4. Secondary Outcome

Title	Number of Participants Who Underwent Major and Minor Amputation
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	180	90
Major amputation	2 1.1%	1 1.1%
Minor amputation	7 3.8%	1 1.1%

5. Secondary Outcome

Title	Number of Participants With Greater Than or Equal to 50 Percent Reduction in Ulcer Surface Area Excluding Intact Skin Healing
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized. LOCF method was used. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	92
Stratum 1 (n= 97, 49)	33 17.9%	15 16.3%
Stratum 2 (n= 39, 19)	8 4.3%	10 10.9%
Stratum 3 (n= 29, 14)	13 7.1%	6 6.5%
Stratum 4 (n= 19, 10)	8 4.3%	2 2.2%

6. Secondary Outcome

Title	Number of Participants Who Died
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	92
Number [participants]	4 2.2%	3 3.3%

7. Secondary Outcome

Title	Number of Participants With Major Cardiovascular Disease Events (MCVE)
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

The data was not analyzed as planned because the study enrollment was terminated before the planned number of randomized participants was obtained.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	0	0

8. Secondary Outcome

Title	Time to Intact Skin Healing
Description	Median time taken to achieve intact skin healing which was defined as 100 percent reduction in ulcer surface area with full epithelialisation.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

The data was not analyzed as planned because the study enrollment was terminated before the planned number of randomized participants was obtained.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	0	0

9. Secondary Outcome

Title	Median Time to First Amputation
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

The data was not analyzed as planned because the study enrollment was terminated before the planned number of randomized participants was obtained.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	0	0

10. Secondary Outcome

Title	Euro Quality of Life-5 Dimensions (EQ-5D)- Utility Score
Description	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.
Time Frame	Baseline and Week 24 (EOT or early termination)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized. Participants were only considered when all items contributing to the score had been answered. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	182	88
Baseline	0.60 (0.26)	0.60 (0.30)
EOT (n= 154, 74)	0.70 (0.22)	0.60 (0.33)

11. Secondary Outcome

Title	Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)
Description	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.
Time Frame	Baseline and Week 24 (EOT or early termination)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized. Participants were only considered when all items contributing to the score had been answered. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	182	91
Baseline	60.20 (18.68)	55.30 (19.72)
EOT (n= 157, 76)	63.30 (18.76)	60.70 (18.02)

12. Secondary Outcome

Title	36-Item Short-Form Health Survey (SF-36) Score
Description	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).
Time Frame	Baseline and Week 24 (EOT or early termination)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized. This was calculated only when more than half of the questions within dimension were answered. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	90
Baseline: Physical Functioning	34.70 (12.06)	32.50 (10.96)
Baseline: Role-Physical	35.40 (11.22)	35.20 (11.41)
Baseline: Bodily Pain	42.30 (11.19)	40.30 (11.52)
Baseline: General Health	42.30 (5.52)	42.60 (5.10)
Baseline: Visibility	48.30 (5.63)	48.70 (5.02)
Baseline: Social Functioning	33.00 (6.49)	33.10 (6.90)
Baseline: Role-Emotional	39.10 (13.48)	38.30 (13.49)
Baseline: Mental Health	41.90 (6.57)	41.30 (6.72)
Baseline: Physical (PCS)	38.10 (9.42)	36.70 (8.75)
Baseline: Mental (MCS)	42.40 (7.26)	42.80 (7.37)
EOT: Physical Functioning (n= 156, 76)	37.10 (11.71)	35.50 (11.39)
EOT: Role-Physical (n= 155, 76)	39.30 (11.25)	37.50 (11.31)
EOT: Bodily Pain (n= 156, 76)	47.50 (10.30)	45.00 (10.73)
EOT: General Health (n= 156, 76)	42.50 (5.10)	42.80 (5.15)
EOT: Visibility (n= 156, 76)	48.20 (5.58)	48.80 (5.15)
EOT: Social Functioning (n= 152, 73)	33.30 (6.13)	32.30 (5.83)
EOT: Role-Emotional (n= 155, 76)	41.20 (13.44)	38.80 (13.48)
EOT: Mental Health (n= 156, 76)	41.90 (6.20)	42.00 (6.80)
EOT: Physical (PCS) (n= 151, 73)	41.70 (9.04)	40.10 (8.60)
EOT: Mental (MCS) (n= 151, 73)	42.10 (6.89)	41.60 (6.46)

13. Secondary Outcome

Title	11-point Likert Pain Scale
Description	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.
Time Frame	Baseline and Week 24 (EOT or early termination)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	183	89
Baseline	4.20 (2.76)	4.50 (2.83)
EOT (n= 155, 75)	2.10 (2.27)	2.50 (2.54)

14. Secondary Outcome

Title	Transcutaneous Local Tissue Oxygenation (pO2)
Description	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.
Time Frame	Baseline and Week 24 (EOT or early termination)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized. Participants were analyzed at selected sites only, based on availability. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the timepoint for each group respectively.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	47	26
Baseline	31.80 (21.29)	36.00 (17.11)
EOT (n= 32, 19)	38.80 (19.58)	39.70 (16.18)

15. Other Pre-specified Outcome

Title	Number of All Hemorrhages
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

Safety analysis population included all participants who were known to have taken at least one dose of the study medication.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	92
Number [hemorrhages]	10	2

16. Other Pre-specified Outcome

Title	Number of Major and Minor Hemorrhages
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

Safety analysis population included all participants who were known to have taken at least one dose of the study medication.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	92
Major hemorrhages	2	0
Minor hemorrhages	8	2

17. Other Pre-specified Outcome

Title	Number of Clinically Relevant Minor Hemorrhages and Trivial Hemorrhages
Description	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.
Time Frame	Week 24 (EOT) or early termination

Outcome Measure Data

Analysis Population Description

Safety analysis population included all participants who were known to have taken at least one dose of the study medication.

Arm/Group Title	Dalteparin	Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).	Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
Measure Participants	184	92
Clinically relevant minor hemorrhages	5	1
Trivial hemorrhages	3	1

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Dalteparin		Placebo
Arm/Group Description	Dalteparin 5000 International Units (IU) (0.2 mL) subcutaneously (s.c.) once daily for 24 weeks or early termination (ET).		Placebo (0.2 mL normal saline) administered s.c. once daily for 24 weeks or ET.
All Cause Mortality
	Dalteparin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dalteparin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/184 (17.9%)		18/92 (19.6%)
Cardiac disorders
Acute myocardial infarction	0/184 (0%)		1/92 (1.1%)
Cardiac failure	2/184 (1.1%)		2/92 (2.2%)
Cardiac failure congestive	1/184 (0.5%)		0/92 (0%)
Myocardial infarction	2/184 (1.1%)		1/92 (1.1%)
Myocardial ischaemia	1/184 (0.5%)		0/92 (0%)
Trifascicular block	0/184 (0%)		1/92 (1.1%)
Eye disorders
Retinal haemorrhage	3/184 (1.6%)		0/92 (0%)
Gastrointestinal disorders
Ascites	1/184 (0.5%)		0/92 (0%)
Colonic stenosis	1/184 (0.5%)		0/92 (0%)
Pancreatitis acute	0/184 (0%)		1/92 (1.1%)
General disorders
Condition aggravated	0/184 (0%)		1/92 (1.1%)
Oedema peripheral	1/184 (0.5%)		1/92 (1.1%)
Ulcer	1/184 (0.5%)		1/92 (1.1%)
Hepatobiliary disorders
Cholelithiasis	0/184 (0%)		1/92 (1.1%)
Infections and infestations
Arteriosclerotic gangrene	1/184 (0.5%)		0/92 (0%)
Cellulitis	5/184 (2.7%)		1/92 (1.1%)
Erysipelas	1/184 (0.5%)		3/92 (3.3%)
Gangrene	4/184 (2.2%)		0/92 (0%)
Infected skin ulcer	3/184 (1.6%)		1/92 (1.1%)
Infection	1/184 (0.5%)		0/92 (0%)
Influenza	0/184 (0%)		1/92 (1.1%)
Localised infection	1/184 (0.5%)		2/92 (2.2%)
Osteomyelitis	1/184 (0.5%)		0/92 (0%)
Pneumonia	2/184 (1.1%)		1/92 (1.1%)
Urinary tract infection	0/184 (0%)		2/92 (2.2%)
Metabolism and nutrition disorders
Diabetes mellitus	1/184 (0.5%)		0/92 (0%)
Diabetic foot	2/184 (1.1%)		0/92 (0%)
Diabetic ketoacidosis	0/184 (0%)		1/92 (1.1%)
Hyperuricaemia	1/184 (0.5%)		0/92 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/184 (0.5%)		0/92 (0%)
Pain in extremity	0/184 (0%)		1/92 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/184 (0.5%)		0/92 (0%)
Nervous system disorders
Cerebrovascular accident	1/184 (0.5%)		0/92 (0%)
Renal and urinary disorders
Renal failure acute	1/184 (0.5%)		0/92 (0%)
Strangury	1/184 (0.5%)		0/92 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/184 (0.5%)		0/92 (0%)
Chronic obstructive pulmonary disease	1/184 (0.5%)		0/92 (0%)
Skin and subcutaneous tissue disorders
Diabetic ulcer	0/184 (0%)		1/92 (1.1%)
Skin necrosis	0/184 (0%)		1/92 (1.1%)
Vascular disorders
Venous thrombosis	1/184 (0.5%)		0/92 (0%)
Other (Not Including Serious) Adverse Events
	Dalteparin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/184 (41.3%)		36/92 (39.1%)
Blood and lymphatic system disorders
Anaemia	1/184 (0.5%)		1/92 (1.1%)
Anaemia of chronic disease	0/184 (0%)		1/92 (1.1%)
Monocytopenia	1/184 (0.5%)		1/92 (1.1%)
Normochromic normocytic anaemia	1/184 (0.5%)		0/92 (0%)
Pancytopenia	1/184 (0.5%)		0/92 (0%)
Cardiac disorders
Angina pectoris	1/184 (0.5%)		0/92 (0%)
Atrial fibrillation	1/184 (0.5%)		1/92 (1.1%)
Bundle branch block left	1/184 (0.5%)		0/92 (0%)
Sinus tachycardia	0/184 (0%)		1/92 (1.1%)
Eye disorders
Eye haemorrhage	1/184 (0.5%)		0/92 (0%)
Retinal haemorrhage	0/184 (0%)		1/92 (1.1%)
Gastrointestinal disorders
Abdominal distension	1/184 (0.5%)		0/92 (0%)
Abdominal pain	1/184 (0.5%)		0/92 (0%)
Abdominal rigidity	1/184 (0.5%)		0/92 (0%)
Diarrhoea	1/184 (0.5%)		0/92 (0%)
Dyspepsia	1/184 (0.5%)		0/92 (0%)
Erosive duodenitis	0/184 (0%)		1/92 (1.1%)
Gastritis	0/184 (0%)		1/92 (1.1%)
Gastrooesophageal reflux disease	1/184 (0.5%)		0/92 (0%)
Nausea	1/184 (0.5%)		0/92 (0%)
Reflux oesophagitis	1/184 (0.5%)		0/92 (0%)
Retching	1/184 (0.5%)		0/92 (0%)
General disorders
Adverse drug reaction	0/184 (0%)		1/92 (1.1%)
Asthenia	1/184 (0.5%)		0/92 (0%)
Disease progression	0/184 (0%)		1/92 (1.1%)
Inflammation	1/184 (0.5%)		0/92 (0%)
Influenza like illness	1/184 (0.5%)		1/92 (1.1%)
Injection site haematoma	7/184 (3.8%)		0/92 (0%)
Injection site pain	1/184 (0.5%)		0/92 (0%)
Oedema	1/184 (0.5%)		1/92 (1.1%)
Oedema peripheral	1/184 (0.5%)		3/92 (3.3%)
Pain	1/184 (0.5%)		1/92 (1.1%)
Ulcer	3/184 (1.6%)		4/92 (4.3%)
Hepatobiliary disorders
Liver disorder	1/184 (0.5%)		0/92 (0%)
Immune system disorders
Hypersensitivity	1/184 (0.5%)		0/92 (0%)
Infections and infestations
Bronchitis	2/184 (1.1%)		0/92 (0%)
Cellulitis	2/184 (1.1%)		0/92 (0%)
Diabetic foot infection	4/184 (2.2%)		2/92 (2.2%)
Erysipelas	4/184 (2.2%)		0/92 (0%)
Gastroenteritis	1/184 (0.5%)		0/92 (0%)
Infected skin ulcer	6/184 (3.3%)		5/92 (5.4%)
Infection	4/184 (2.2%)		0/92 (0%)
Influenza	0/184 (0%)		1/92 (1.1%)
Laryngitis	1/184 (0.5%)		0/92 (0%)
Localised infection	3/184 (1.6%)		3/92 (3.3%)
Lower respiratory tract infection	1/184 (0.5%)		0/92 (0%)
Lymphangitis	1/184 (0.5%)		0/92 (0%)
Nasopharyngitis	0/184 (0%)		1/92 (1.1%)
Orchitis	1/184 (0.5%)		0/92 (0%)
Osteomyelitis	1/184 (0.5%)		0/92 (0%)
Osteomyelitis chronic	0/184 (0%)		1/92 (1.1%)
Pharyngitis	1/184 (0.5%)		0/92 (0%)
Pneumonia	1/184 (0.5%)		1/92 (1.1%)
Respiratory tract infection	1/184 (0.5%)		1/92 (1.1%)
Staphylococcal infection	1/184 (0.5%)		0/92 (0%)
Upper respiratory tract infection	1/184 (0.5%)		0/92 (0%)
Urinary tract infection	1/184 (0.5%)		2/92 (2.2%)
Viral upper respiratory tract infection	0/184 (0%)		1/92 (1.1%)
Wound infection	3/184 (1.6%)		2/92 (2.2%)
Injury, poisoning and procedural complications
Contusion	2/184 (1.1%)		2/92 (2.2%)
Excoriation	0/184 (0%)		1/92 (1.1%)
Fall	1/184 (0.5%)		0/92 (0%)
Foot fracture	2/184 (1.1%)		0/92 (0%)
Head injury	1/184 (0.5%)		0/92 (0%)
Joint injury	1/184 (0.5%)		0/92 (0%)
Limb injury	1/184 (0.5%)		1/92 (1.1%)
Muscle rupture	1/184 (0.5%)		0/92 (0%)
Muscle strain	1/184 (0.5%)		0/92 (0%)
Overdose	1/184 (0.5%)		0/92 (0%)
Skin laceration	0/184 (0%)		1/92 (1.1%)
Spinal fracture	1/184 (0.5%)		0/92 (0%)
Subcutaneous haematoma	1/184 (0.5%)		0/92 (0%)
Traumatic haematoma	1/184 (0.5%)		0/92 (0%)
Wound complication	1/184 (0.5%)		0/92 (0%)
Investigations
Antibiotic resistant Staphylococcus test positive	1/184 (0.5%)		0/92 (0%)
Bacterial test positive	1/184 (0.5%)		0/92 (0%)
Blood albumin decreased	0/184 (0%)		1/92 (1.1%)
Blood creatinine increased	1/184 (0.5%)		0/92 (0%)
Blood glucose abnormal	1/184 (0.5%)		0/92 (0%)
C-reactive protein increased	0/184 (0%)		1/92 (1.1%)
Fibrin D dimer increased	1/184 (0.5%)		2/92 (2.2%)
Haemoglobin decreased	1/184 (0.5%)		0/92 (0%)
Heart rate decreased	0/184 (0%)		1/92 (1.1%)
Platelet count increased	0/184 (0%)		1/92 (1.1%)
Weight decreased	1/184 (0.5%)		0/92 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/184 (0%)		1/92 (1.1%)
Diabetic foot	3/184 (1.6%)		1/92 (1.1%)
Hypercholesterolaemia	1/184 (0.5%)		0/92 (0%)
Hyperkalaemia	3/184 (1.6%)		0/92 (0%)
Hyperlipidaemia	1/184 (0.5%)		0/92 (0%)
Hyperuricaemia	1/184 (0.5%)		0/92 (0%)
Hypoglycaemia	3/184 (1.6%)		1/92 (1.1%)
Hypokalaemia	1/184 (0.5%)		0/92 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/184 (0.5%)		0/92 (0%)
Back pain	1/184 (0.5%)		0/92 (0%)
Bone pain	1/184 (0.5%)		0/92 (0%)
Joint swelling	2/184 (1.1%)		0/92 (0%)
Muscle spasms	1/184 (0.5%)		0/92 (0%)
Musculoskeletal chest pain	1/184 (0.5%)		0/92 (0%)
Musculoskeletal pain	1/184 (0.5%)		0/92 (0%)
Neck pain	1/184 (0.5%)		0/92 (0%)
Pain in extremity	5/184 (2.7%)		2/92 (2.2%)
Rhabdomyolysis	0/184 (0%)		1/92 (1.1%)
Tendonitis	1/184 (0.5%)		0/92 (0%)
Nervous system disorders
Dizziness	1/184 (0.5%)		0/92 (0%)
Headache	1/184 (0.5%)		0/92 (0%)
IIIrd nerve paralysis	1/184 (0.5%)		0/92 (0%)
Psychiatric disorders
Anxiety	0/184 (0%)		1/92 (1.1%)
Depressed mood	1/184 (0.5%)		0/92 (0%)
Depression	0/184 (0%)		1/92 (1.1%)
Generalised anxiety disorder	1/184 (0.5%)		0/92 (0%)
Insomnia	2/184 (1.1%)		0/92 (0%)
Sleep disorder	1/184 (0.5%)		1/92 (1.1%)
Renal and urinary disorders
Diabetic nephropathy	1/184 (0.5%)		0/92 (0%)
Renal failure acute	1/184 (0.5%)		0/92 (0%)
Renal failure chronic	1/184 (0.5%)		0/92 (0%)
Urinary tract disorder	1/184 (0.5%)		0/92 (0%)
Reproductive system and breast disorders
Genital haemorrhage	1/184 (0.5%)		0/92 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/184 (0.5%)		0/92 (0%)
Dyspnoea	2/184 (1.1%)		0/92 (0%)
Dyspnoea exertional	0/184 (0%)		1/92 (1.1%)
Epistaxis	1/184 (0.5%)		1/92 (1.1%)
Oropharyngeal pain	1/184 (0.5%)		0/92 (0%)
Sinus congestion	1/184 (0.5%)		0/92 (0%)
Skin and subcutaneous tissue disorders
Blood blister	0/184 (0%)		1/92 (1.1%)
Diabetic ulcer	0/184 (0%)		1/92 (1.1%)
Hyperkeratosis	1/184 (0.5%)		0/92 (0%)
Pruritus generalised	1/184 (0.5%)		0/92 (0%)
Rash	0/184 (0%)		1/92 (1.1%)
Skin lesion	2/184 (1.1%)		0/92 (0%)
Skin ulcer	12/184 (6.5%)		3/92 (3.3%)
Skin ulcer haemorrhage	1/184 (0.5%)		0/92 (0%)
Vascular disorders
Flushing	0/184 (0%)		1/92 (1.1%)
Haematoma	1/184 (0.5%)		0/92 (0%)
Haemorrhage	1/184 (0.5%)		0/92 (0%)
Hypotension	1/184 (0.5%)		0/92 (0%)
Peripheral ischaemia	0/184 (0%)		1/92 (1.1%)
Phlebitis	1/184 (0.5%)		0/92 (0%)

Limitations/Caveats

Study enrollment was terminated before planned number of participants was obtained. Although randomized participants were allowed to complete entire course of therapy according to protocol and study status was therefore designated as completed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.