Evaluation of Dalteparin for Long-term (One Year) Treatment of Blood Clots in Subjects With Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00942968
• Collaborator: (none)
• Enrollment: 338
• Locations: 42
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the long term tolerability and safety of dalteparin in subjects with cancer.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: dalteparin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 338 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: FRAG-A001-401: Dalteparin Sodium Injection (Fragmin), Multicenter, Open-Label, Single-arm, Long Term (52 Weeks) Study for Understanding the Safety and Efficacy in Subjects With Malignancies and Symptomatic Venous Thromboembolism
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: dalteparin; Daily subcutaneous injection 200IU/kg dalteparin

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee [Month 2 up to Month 6]

   A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of greater than or equal to (>=) 2 gram per deciliter (g/dL), 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.

2. Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee [Month 7 up to Month 12]

   A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.

3. Number of Participants With New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee [Month 7 up to Month 12]

   VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (adjudicated by Central Adjudication Committee) were reported.

Secondary Outcome Measures

1. Number of Participants With Investigator Identified Major Bleeding Events [Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12]

   A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (identified by investigator) were reported.

2. Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee [Month 1 up to Month 6, Month 7 up to Month 12, Month 1 up to Month 12, Month 2 up to Month 6, and Month 2 up to Month 12]

   A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding. In this outcome measure, number of participants with any (major or minor) bleeding events (adjudicated by Central Adjudication Committee) were reported.

3. Number of Participants With Fatal Bleeding Events [Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12]

   Fatal bleeding events refers to those bleeding events which leads to death of participant. In this outcome measure, number of participants with fatal bleeding events were reported.

4. Time to First Occurrence of Major Bleeding Event Adjudicated by Central Adjudication Committee [Month 1 up to Month 12]

   Time to first occurrence of major bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first major bleeding event. A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death.

5. Time to First Occurrence of Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee [Month 1 up to Month 12]

   Time to first occurrence of any bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first bleeding event (major or minor). A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding.

6. Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) [Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12]

   VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (identified by investigator) were reported.

7. Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee [Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12]

   VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (adjudicated by Central Adjudication Committee) were reported.

8. Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) [Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12]

   VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (identified by investigator) were reported.

9. Time to First Occurrence of New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee [Month 1 up to Month 12]

   Time to first occurrence of new or recurrent VTE was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE. VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram.

10. Time to First Occurrence of New or Recurrent VTE or CVT Adjudicated by Central Adjudication Committee [Month 1 up to Month 12]

    Time to first occurrence of new or recurrent VTE or CVT was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE or CVT. VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE) .DVT is a blood clot in the deep veins of the leg. If a DVT clot that breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan, contrast venography or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography.

Other Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Baseline (Day 1) up to Week 52]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

2. Number of Participants With Clinically Significant Laboratory Abnormalities [Baseline (Day 1) up to Week 52]

   Criteria for abnormality: Hemoglobin greater than or equal to(>=)130*lower limit of normal(LLN); less than or equal to(<=)170*upper limit of normal(ULN), hematocrit >=0.39*LLN;<=0.51*ULN, red blood cell >=4.5*LLN;<=5.9*ULN, platelet>=150*LLN;<= 450*ULN, white blood cells >=4*LLN;<=11*ULN; lymphocytes>=0.09;<=0.44, neutrophils=>0.16*LLN;<=0.7*ULN, eosinophils<=0.04*ULN, basophils<=0.02*ULN, monocytes>0.08*ULN; bilirubin >=5.1*LLN;<=22.2*ULN, aspartate aminotransferase >=13*LLN;<=36*ULN, alanine aminotransferase>=11*LLN;<=54*ULN, alkaline phosphatase>=31*LLN ;<=104 *ULN, total protein>=60*LLN; <=76*ULN, albumin=>35*LLN;<=50*ULN, glucose>=3.77 ;<=6.05;blood urea nitrogen>=1.785*LLN;<=7.5*ULN, creatinine>=70.7*LLN;<=114.9*ULN, creatinine kinase>=30*LLN ;<=280*ULN, lactate dehydrogenase>=85*LLN;<=180*ULN, sodium>=137*LLN ;<=144*ULN, potassium >=3.5*LLN;<=5*ULN, chloride>=102*LLN;<=111*ULN, calcium>=2.22*LLN ;<=2.57*ULN, phosphorus=>0.81 ;<=1.45); nitrogen cholesterol>=1.78*LLN ;<=7.49*ULN.

3. Number of Participants With Abnormal Physical Examinations Findings [Baseline (Day 1), Week 1, 4, 8, 12, 24, 36, 48, 52]

   Physical examinations included head, ears, nose, throat (ENT), neck, heart, chest, lungs, abdomen, extremities, neurological systems, skin, general appearance and others (thigh, abdomen unobtrusive scar, breast, cardio-vascular, constitutional, face, genitalia, genitourinary, gastrointestinal, hematologic, left ankle unobtrusive scar, lymph nodes, lymphatic, malaise/fatigue, mouth, musculoskeletal, musculoskeletal, peripherally inserted central catheters line site left arm, psychiatric, skeletal, urinary, weight, activity level, bladder irritation, dyspnea and eastern cooperative oncology group performance status [used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead]). Abnormality in physical examinations was based on investigator's discretion.

4. Other Pre-specified: Number of Participants With Clinically Significant Electrocardiogram Findings [Baseline up to Week 52]

   Clinically significant ECG findings included: corrected QT (QTc) > 450 ms, QTc >500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms.

5. Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants [Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52]

   Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Male and female subjects, age greater than or equal to 18 years of age.

2. Females should be either of non-childbearing potential as a result of surgery, radiation therapy, menopause (one year post onset), or of childbearing potential and willing to adhere to an acceptable method of pregnancy prevention.

3. Subjects must be newly diagnosed, symptomatic proximal deep-vein thrombosis of the lower extremity, pulmonary embolism, or both.

4. Subjects must have active malignancy defined as a diagnosis of cancer (excluding basal cell or squamous cell carcinoma of the skin) within six months before enrollment, having received any treatment for cancer within the previous six months, or having documented recurrent or metastatic cancer.

5. Prior to enrollment, subjects must not have received therapeutic doses of anticoagulant therapy (including low molecular weight heparin [LMWH]) for >48 hours (or >4 doses within 48 hours).

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

7. Subjects must have a life expectancy of >6 months.

8. Subjects must have a platelet count of >75,000 mm^3.

9. The subject must not be on any oral anticoagulant therapy for concomitant diseases.

10. Subjects must have no active or serious bleeding episodes within two weeks prior to study entry.

11. Subjects must be able to comply with scheduled follow-ups.

Exclusion Criteria:

1. Subjects who have a high risk of serious bleeding (e.g., recent neurosurgery within 30 days, history of intracranial hemorrhage, acute gastroduodenal ulcer, etc.).

2. Subjects who are on hemodialysis.

3. Subjects who have a prior placement of a Greenfield filter or other device to prevent embolization of deep vein thromboses.

4. Subjects with a known contraindication to the use of heparin (e.g., heparin-induced thrombocytopenia).

5. Subjects with a known hypersensitivity to heparin, dalteparin sodium, other LMWHs or pork products.

6. Subjects who are currently participating in another clinical trial involving anticoagulation therapy (with the exception of acetylsalicylic acid (ASA) in the 30 days prior to study entry, or who are actively using any investigational drugs/treatments 30 days prior to study entry involving anticoagulation therapy (with the exception of ASA , t.i.d).

7. Subject is pregnant or breast feeding.

8. Subjects with uncontrolled hypertension characterized by a sustained systolic pressure

170 mmHg and/or diastolic pressure >100 mmHg.

1. Subjects with a serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the subject's ability to complete the study.

2. Any condition that makes the subject unsuitable in the opinion of the investigator.

3. Subjects with leukemia or myeloproliferative syndrome.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tuscon	Arizona	United States	85719
2	Bay Area Cancer Research Group	Pleasant Hill	California	United States	94523
3	Harbor-UCLA Medical Center	Torrance	California	United States	90509
4	University of CT Health Center	Farmington	Connecticut	United States	6030
5	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	6360
6	Georgetown University Hospital-Lombardi Cancer Ctr	Washington	District of Columbia	United States	20007
7	Halifax Health	Daytona Beach	Florida	United States	32114
8	Atlanta Institute for Medical Research	Decatur	Georgia	United States	30030
9	Orchard Healthcare Research Inc.	Skokie	Illinois	United States	60076
10	James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
11	Bringham and Women's Hospital	Boston	Massachusetts	United States	2115
12	Henry Ford Hospital K-15	Detroit	Michigan	United States	48202
13	University of Rochester Medical Center	Rochester	New York	United States	14642
14	Stony Brook University, Medical Center	Stony Brook	New York	United States	11794
15	Duke University Medical Center	Durham	North Carolina	United States	27710
16	MidDakota Clinic	Bismarck	North Dakota	United States	58501
17	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania	United States	19106
18	MD Anderson Cancer Center	Houston	Texas	United States	77030
19	University of Utah	Salt Lake City	Utah	United States	84132
20	Vermont Cancer Center at Fletcher Allen Health Care	Burlington	Vermont	United States	5401
21	University of Virginia	Charlottesville	Virginia	United States	22908
22	LKH Graz Univrsitatstklinik fur Innere Medizin	Graz		Austria
23	Medizinische Universitat Innsbruck Studienambulanz Hamatologie	Innsbruck		Austria
24	KH d. Elizabethinen Linz GmbH Servicestelle fur klin. Studien und Universitare Angelegenheiten	Linz		Austria
25	KH der Barmherzigen Schwestern	Linz		Austria
26	Dialysestation Landesklinkum St.Poelten	St. Poelten		Austria
27	Medizinische Universitat Wien	Vienna		Austria
28	University of Alberta	Edmonton	Alberta	Canada
29	Vancouver General Hospital	Vancouver	British Columbia	Canada
30	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada
31	London Health Sciences Centre	London	Ontario	Canada
32	Ottawa Health Research Institute	Ottawa	Ontario	Canada
33	University Health Network-Toronto General Hospital	Toronto	Ontario	Canada
34	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada
35	Sir Mortimer B. Davis Jewish General Hospital	Montreal	Quebec	Canada
36	Gelre Ziekenhuizen-Locatie Apeldoorn	Apeldoorn		Netherlands
37	Orbis Medisch Centrum, Sittard-Geleen	Sittard-Geleen		Netherlands
38	Hospital clinic i Provincial de Agencia de Ensayos Clinicos	Barcelona		Spain
39	Hospital General Santa Maria del Rosell	Caragena (Murcia)		Spain
40	Hospital Virgen de la Arrixaca	El Palmar (Murcia)		Spain
41	Hospital Universitari Dr Josep Trueta	Girona		Spain
42	Clinica Universitaria de Navarra	Pamplona		Spain

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer
• Study Director: Gary Palmer, MD, Medical Affairs, Eisai, Inc

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: NCT00942968
• Other Study ID Numbers: FRAG-A001-401; A6301095
• First Posted: Jul 21, 2009
• Last Update Posted: Feb 24, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight

Study Results

Participant Flow

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Period Title: Overall Study
STARTED	338
Treated	334
COMPLETED	109
NOT COMPLETED	229

Baseline Characteristics

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Overall Participants	334
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (10.63)
Gender (Count of Participants)
Female	171 51.2%
Male	163 48.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee
Description	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of greater than or equal to (>=) 2 gram per deciliter (g/dL), 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.
Time Frame	Month 2 up to Month 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Number [participants]	14 4.2%

2. Primary Outcome

Title	Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee
Description	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.
Time Frame	Month 7 up to Month 12

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Number [participants]	8 2.4%

3. Primary Outcome

Title	Number of Participants With New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee
Description	VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (adjudicated by Central Adjudication Committee) were reported.
Time Frame	Month 7 up to Month 12

Outcome Measure Data

Analysis Population Description

Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	194
Number [participants]	8 2.4%

4. Secondary Outcome

Title	Number of Participants With Investigator Identified Major Bleeding Events
Description	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (identified by investigator) were reported.
Time Frame	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Month 1 up to Month 6	28 8.4%
Month 7 up to Month 12	7 2.1%
Month 1 up to Month 12	35 10.5%
Month 2 up to Month 6	15 4.5%
Month 2 up to Month 12	22 6.6%

5. Secondary Outcome

Title	Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee
Description	A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding. In this outcome measure, number of participants with any (major or minor) bleeding events (adjudicated by Central Adjudication Committee) were reported.
Time Frame	Month 1 up to Month 6, Month 7 up to Month 12, Month 1 up to Month 12, Month 2 up to Month 6, and Month 2 up to Month 12

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Month 1 up to Month 6	91 27.2%
Month 7 up to Month 12	21 6.3%
Month 1 up to Month 12	112 33.5%
Month 2 up to Month 6	47 14.1%
Month 2 up to Month 12	68 20.4%

6. Secondary Outcome

Title	Number of Participants With Fatal Bleeding Events
Description	Fatal bleeding events refers to those bleeding events which leads to death of participant. In this outcome measure, number of participants with fatal bleeding events were reported.
Time Frame	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Month 1 up to Month 6	1 0.3%
Month 7 up to Month 12	1 0.3%
Month 1 up to Month 12	2 0.6%
Month 2 up to Month 6	1 0.3%
Month 2 up to Month 12	2 0.6%

7. Secondary Outcome

Title	Time to First Occurrence of Major Bleeding Event Adjudicated by Central Adjudication Committee
Description	Time to first occurrence of major bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first major bleeding event. A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death.
Time Frame	Month 1 up to Month 12

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Mean (Standard Error) [days]	332.9 (5.25)

8. Secondary Outcome

Title	Time to First Occurrence of Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee
Description	Time to first occurrence of any bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first bleeding event (major or minor). A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of >=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding.
Time Frame	Month 1 up to Month 12

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Mean (Standard Error) [days]	262.5 (8.52)

9. Secondary Outcome

Title	Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs)
Description	VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (identified by investigator) were reported.
Time Frame	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12

Outcome Measure Data

Analysis Population Description

Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'n' signifies those participants who were evaluable at specified time intervals.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Month 1 up to Month 6 (n=334)	29 8.7%
Month 7 up to Month 12 (n=195)	8 2.4%
Month 1 up to Month 12 (n=334)	37 11.1%
Month 2 up to Month 6 (n=295)	9 2.7%
Month 2 up to Month 12 (n=295)	17 5.1%

10. Secondary Outcome

Title	Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee
Description	VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (adjudicated by Central Adjudication Committee) were reported.
Time Frame	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12

Outcome Measure Data

Analysis Population Description

Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'n' signifies those participants who were evaluable at specified time intervals.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Month 1 up to Month 6 (n=334)	29 8.7%
Month 7 up to Month 12 (n=194)	8 2.4%
Month 1 up to Month 12 (n=334)	37 11.1%
Month 2 up to Month 6 (n=296)	10 3%
Month 2 up to Month 12 (n=296)	18 5.4%

11. Secondary Outcome

Title	Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT)
Description	VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (identified by investigator) were reported.
Time Frame	Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12

Outcome Measure Data

Analysis Population Description

Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'n' signifies those participants who were evaluable at specified time intervals.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Month 1 up to Month 6 (n=334)	29 8.7%
Month 7 up to Month 12 (n=195)	8 2.4%
Month 1 up to Month 12 (n=334)	37 11.1%
Month 2 up to Month 6 (n=295)	9 2.7%
Month 2 up to Month 12 (n=295)	17 5.1%

12. Secondary Outcome

Title	Time to First Occurrence of New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee
Description	Time to first occurrence of new or recurrent VTE was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE. VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram.
Time Frame	Month 1 up to Month 12

Outcome Measure Data

Analysis Population Description

Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Mean (Standard Error) [days]	294.1 (4.87)

13. Secondary Outcome

Title	Time to First Occurrence of New or Recurrent VTE or CVT Adjudicated by Central Adjudication Committee
Description	Time to first occurrence of new or recurrent VTE or CVT was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE or CVT. VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE) .DVT is a blood clot in the deep veins of the leg. If a DVT clot that breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan, contrast venography or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography.
Time Frame	Month 1 up to Month 12

Outcome Measure Data

Analysis Population Description

Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Mean (Standard Error) [days]	294.1 (4.87)

14. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Time Frame	Baseline (Day 1) up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
AE	328 98.2%
SAE	213 63.8%

15. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities
Description	Criteria for abnormality: Hemoglobin greater than or equal to(>=)130*lower limit of normal(LLN); less than or equal to(<=)170*upper limit of normal(ULN), hematocrit >=0.39*LLN;<=0.51*ULN, red blood cell >=4.5*LLN;<=5.9*ULN, platelet>=150*LLN;<= 450*ULN, white blood cells >=4*LLN;<=11*ULN; lymphocytes>=0.09;<=0.44, neutrophils=>0.16*LLN;<=0.7*ULN, eosinophils<=0.04*ULN, basophils<=0.02*ULN, monocytes>0.08*ULN; bilirubin >=5.1*LLN;<=22.2*ULN, aspartate aminotransferase >=13*LLN;<=36*ULN, alanine aminotransferase>=11*LLN;<=54*ULN, alkaline phosphatase>=31*LLN ;<=104 *ULN, total protein>=60*LLN; <=76*ULN, albumin=>35*LLN;<=50*ULN, glucose>=3.77 ;<=6.05;blood urea nitrogen>=1.785*LLN;<=7.5*ULN, creatinine>=70.7*LLN;<=114.9*ULN, creatinine kinase>=30*LLN ;<=280*ULN, lactate dehydrogenase>=85*LLN;<=180*ULN, sodium>=137*LLN ;<=144*ULN, potassium >=3.5*LLN;<=5*ULN, chloride>=102*LLN;<=111*ULN, calcium>=2.22*LLN ;<=2.57*ULN, phosphorus=>0.81 ;<=1.45); nitrogen cholesterol>=1.78*LLN ;<=7.49*ULN.
Time Frame	Baseline (Day 1) up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Number [participants]	0 0%

16. Other Pre-specified Outcome

Title	Number of Participants With Abnormal Physical Examinations Findings
Description	Physical examinations included head, ears, nose, throat (ENT), neck, heart, chest, lungs, abdomen, extremities, neurological systems, skin, general appearance and others (thigh, abdomen unobtrusive scar, breast, cardio-vascular, constitutional, face, genitalia, genitourinary, gastrointestinal, hematologic, left ankle unobtrusive scar, lymph nodes, lymphatic, malaise/fatigue, mouth, musculoskeletal, musculoskeletal, peripherally inserted central catheters line site left arm, psychiatric, skeletal, urinary, weight, activity level, bladder irritation, dyspnea and eastern cooperative oncology group performance status [used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (<) 50 percent (%) of the time; 3= in bed for greater than (>) 50% of the time; 4= 100% bedridden; 5= dead]). Abnormality in physical examinations was based on investigator's discretion.
Time Frame	Baseline (Day 1), Week 1, 4, 8, 12, 24, 36, 48, 52

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium. Here 'n' signifies those participants who were evaluable at specified categories.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Baseline : Head (n=327)	14 4.2%
Baseline : Ears, nose, throat (ENT)(n=327)	20 6%
Baseline : Neck (n=327)	10 3%
Baseline : Heart (n=327)	26 7.8%
Baseline : Chest (n=326)	40 12%
Baseline : Lungs (n=327)	65 19.5%
Baseline : Abdomen (n=327)	73 21.9%
Baseline : Extremities (n=328)	203 60.8%
Baseline : Neurological systems (n=327)	18 5.4%
Baseline : Skin (n=327)	51 15.3%
Baseline : General appearance (n=327)	47 14.1%
Baseline : Others (n=47)	25 7.5%
Week 1 : Head (n=213)	16 4.8%
Week 1 : ENT (n=214)	20 6%
Week 1 : Neck (n=214)	7 2.1%
Week 1 : Heart (n=214)	10 3%
Week 1 : Chest (n=213)	22 6.6%
Week 1 : Lungs (n=214)	28 8.4%
Week 1 :Abdomen (n=214)	62 18.6%
Week 1 : Extremities (n=213)	103 30.8%
Week 1 : Neurological systems (n=213)	16 4.8%
Week 1 : Skin (n=213)	52 15.6%
Week 1 : General appearance (n=212)	25 7.5%
Week 1:Others (n=41)	23 6.9%
Week 4 : Head (n=211)	12 3.6%
Week 4 : ENT (n=211)	16 4.8%
Week 4 : Neck (n=211)	6 1.8%
Week 4 : Heart (n=210)	8 2.4%
Week 4 : Chest (n=211)	23 6.9%
Week 4 : Lungs (n=211)	24 7.2%
Week 4 : Abdomen (n=210)	59 17.7%
Week 4 : Extremities (n=211)	83 24.9%
Week 4 : Neurological systems (n=211)	9 2.7%
Week 4 : Skin (n=210)	49 14.7%
Week 4 : General appearance (n=208)	25 7.5%
Week 4 : Others (n=23)	20 6%
Week 8 : Head (n=186)	11 3.3%
Week 8 : ENT (n=186)	16 4.8%
Week 8 : Neck (n=185)	4 1.2%
Week 8 : Heart (n=186)	8 2.4%
Week 8 : Chest (n=186)	21 6.3%
Week 8 : Lungs (n=186)	31 9.3%
Week 8 : Abdomen (n=186)	49 14.7%
Week 8 : Extremities (n=186)	80 24%
Week 8 : Neurological systems (n=185)	13 3.9%
Week 8 : Skin (n=186)	38 11.4%
Week 8 : General appearance (n=186)	16 4.8%
Week 8 : Others (n=16)	12 3.6%
Week 12 : Head (n=183)	10 3%
Week 12 : ENT (n=183)	12 3.6%
Week 12 : Neck (n=183)	1 0.3%
Week 12 : Heart (n=183)	9 2.7%
Week 12 : Chest (n=183)	22 6.6%
Week 12 : Lungs (n=183)	15 4.5%
Week 12 : Abdomen (n=183)	47 14.1%
Week 12 : Extremities (n=183)	57 17.1%
Week 12 : Neurological systems (n=183)	19 5.7%
Week 12 : Skin (n=183)	39 11.7%
Week 12 : General appearance (n=182)	18 5.4%
Week 12 : Other (n=27)	16 4.8%
Week 24 : Head (n=166)	2 0.6%
Week 24 : ENT (n=166)	12 3.6%
Week 24 : Neck (n=166)	4 1.2%
Week 24 : Heart (n=166)	9 2.7%
Week 24 : Chest (n=166)	17 5.1%
Week 24 : Lungs (n=166)	14 4.2%
Week 24 : Abdomen (n=166)	37 11.1%
Week 24 : Extremities (n=166)	47 14.1%
Week 24 : Neurological systems (n=166)	14 4.2%
Week 24 : Skin (n=166)	35 10.5%
Week 24 : General appearance (n=166)	9 2.7%
Week 24 : Others (n=17)	11 3.3%
Week 36 : Head (n=127)	6 1.8%
Week 36 : ENT (n=127)	9 2.7%
Week 36 : Neck (n=127)	4 1.2%
Week 36 : Heart (n=127)	7 2.1%
Week 36 : Chest (n=127)	18 5.4%
Week 36 : Lungs (n=127)	12 3.6%
Week 36 : Abdomen (n=126)	35 10.5%
Week 36 : Extremities (n=127)	37 11.1%
Week 36 : Neurological systems (n=127)	9 2.7%
Week 36 : Skin (n=127)	32 9.6%
Week 36 : General appearance (n=126)	11 3.3%
Week 36 : Others (n=14)	9 2.7%
Week 48 : Head (n=103)	2 0.6%
Week 48 : ENT (n=103)	6 1.8%
Week 48 : Neck (n=103)	3 0.9%
Week 48 : Heart (n=103)	7 2.1%
Week 48 : Chest (n=103)	11 3.3%
Week 48 : Lungs (n=102)	14 4.2%
Week 48 : Abdomen (n=103)	27 8.1%
Week 48 : Extremities (n=103)	29 8.7%
Week 48 : Neurological systems (n=103)	8 2.4%
Week 48 : Skin (n=103)	29 8.7%
Week 48 : General appearance (n=103)	9 2.7%
Week 48 : Others (n=7)	3 0.9%
Week 52 : Head (n=193)	7 2.1%
Week 52 : ENT (n=193)	13 3.9%
Week 52 : Neck (n=193)	5 1.5%
Week 52 : Heart (n=193)	12 3.6%
Week 52 : Chest (n=193)	23 6.9%
Week 52 : Lungs (n=191)	23 6.9%
Week 52 : Abdomen (n=193)	60 18%
Week 52 : Extremities (n=193)	68 20.4%
Week 52 : Neurological systems (n=193)	24 7.2%
Week 52 : Skin (n=193)	38 11.4%
Week 52 : General appearance (n=193)	27 8.1%
Week 52 : Others (n=25)	15 4.5%

17. Other Pre-specified Outcome

Title	Other Pre-specified: Number of Participants With Clinically Significant Electrocardiogram Findings
Description	Clinically significant ECG findings included: corrected QT (QTc) > 450 ms, QTc >500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 treatment with dalteparin sodium.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	334
Number [participants]	8 2.4%

18. Other Pre-specified Outcome

Title	Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants
Description	Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age.
Time Frame	Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Outcome Measure Data

Analysis Population Description

Severely renal-impaired population included all participants who had at least 1 dose of study drug and had severe renal impairment at the baseline or developed severe renal impairment (CrCl) < 30 milliliter per minute during the study. Here, n' signifies those participants who were evaluable at specified time points.

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
Measure Participants	19
Baseline (n=17)	46.0 (28.66)
Week 4 (n=15)	-8.6 (25.39)
Week 8 (n=13)	2.5 (47.02)
Week 12 (n=13)	2.1 (58.15)
Week 16 (n=4)	-9.2 (21.93)
Week 20 (n=2)	7.7 (7.90)
Week 24 (n=12)	4.5 (49.62)
Week 28 (n=1)	-44.0 (NA)
Week 32 (n=1)	-14.0 (NA)
Week 36 (n=8)	5.8 (56.91)
Week 40 (n=2)	-21.0 (9.90)
Week 44 (n=2)	-20.0 (4.24)
Week 48 (n=6)	-26.0 (18.12)
Week 52 (n=11)	4.8 (50.19)

Adverse Events

Arm/Group Title	Dalteparin Sodium
Arm/Group Description	Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52.
All Cause Mortality
	Dalteparin Sodium
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dalteparin Sodium
	Affected / at Risk (%)	# Events
Total	213/334 (63.8%)
Blood and lymphatic system disorders
Anaemia	6/334 (1.8%)
Bone marrow failure	1/334 (0.3%)
Febrile neutropenia	12/334 (3.6%)
Heparin-induced thrombocytopenia	2/334 (0.6%)
Leukocytosis	1/334 (0.3%)
Neutropenia	4/334 (1.2%)
Pancytopenia	3/334 (0.9%)
Thrombocytopenia	4/334 (1.2%)
Cardiac disorders
Acute myocardial infarction	1/334 (0.3%)
Angina pectoris	1/334 (0.3%)
Atrial fibrillation	1/334 (0.3%)
Atrial flutter	2/334 (0.6%)
Cardiac failure congestive	2/334 (0.6%)
Cardio-respiratory arrest	1/334 (0.3%)
Coronary artery occlusion	1/334 (0.3%)
Endocarditis noninfective	1/334 (0.3%)
Myocardial infarction	1/334 (0.3%)
Ear and labyrinth disorders
Vertigo	1/334 (0.3%)
Endocrine disorders
Adrenal haemorrhage	1/334 (0.3%)
Gastrointestinal disorders
Abdominal pain	2/334 (0.6%)
Ascites	5/334 (1.5%)
Colitis	1/334 (0.3%)
Colonic obstruction	1/334 (0.3%)
Diarrhoea	7/334 (2.1%)
Diarrhoea haemorrhagic	1/334 (0.3%)
Duodenal obstruction	1/334 (0.3%)
Gastric ulcer haemorrhage	2/334 (0.6%)
Gastritis	1/334 (0.3%)
Gastrointestinal haemorrhage	4/334 (1.2%)
Gastrointestinal necrosis	1/334 (0.3%)
Gastrooesophageal reflux disease	1/334 (0.3%)
Haematemesis	1/334 (0.3%)
Intestinal obstruction	3/334 (0.9%)
Intestinal perforation	2/334 (0.6%)
Intra-abdominal haemorrhage	1/334 (0.3%)
Lower gastrointestinal haemorrhage	1/334 (0.3%)
Narcotic bowel syndrome	1/334 (0.3%)
Nausea	5/334 (1.5%)
Oesophageal obstruction	1/334 (0.3%)
Pancreatic mass	1/334 (0.3%)
Pancreatitis	1/334 (0.3%)
Peritoneal haemorrhage	2/334 (0.6%)
Rectal haemorrhage	3/334 (0.9%)
Rectal ulcer haemorrhage	1/334 (0.3%)
Small intestinal obstruction	5/334 (1.5%)
Subileus	1/334 (0.3%)
Upper gastrointestinal haemorrhage	3/334 (0.9%)
Varicose veins of abdominal wall	1/334 (0.3%)
Vomiting	8/334 (2.4%)
Small intestinal perforation	1/334 (0.3%)
General disorders
Asthenia	1/334 (0.3%)
Chills	1/334 (0.3%)
Device malfunction	1/334 (0.3%)
Device occlusion	2/334 (0.6%)
Disease progression	29/334 (8.7%)
Fatigue	1/334 (0.3%)
General physical health deterioration	1/334 (0.3%)
Mucosal inflammation	2/334 (0.6%)
Multi-organ failure	2/334 (0.6%)
Oedema peripheral	4/334 (1.2%)
Pain	2/334 (0.6%)
Pyrexia	5/334 (1.5%)
Hepatobiliary disorders
Bile duct obstruction	2/334 (0.6%)
Cholecystitis	1/334 (0.3%)
Cholelithiasis	2/334 (0.6%)
Cholestasis	1/334 (0.3%)
Gallbladder disorder	1/334 (0.3%)
Hepatic failure	1/334 (0.3%)
Jaundice	1/334 (0.3%)
Infections and infestations
Appendicitis	1/334 (0.3%)
Bacteraemia	1/334 (0.3%)
Bacterial infection	1/334 (0.3%)
Bacterial sepsis	1/334 (0.3%)
Bronchitis	1/334 (0.3%)
Candiduria	2/334 (0.6%)
Cellulitis	12/334 (3.6%)
Clostridial infection	2/334 (0.6%)
Clostridium difficile colitis	1/334 (0.3%)
Device related infection	1/334 (0.3%)
Diverticulitis	1/334 (0.3%)
Escherichia sepsis	1/334 (0.3%)
Gastroenteritis	1/334 (0.3%)
Gastroenteritis viral	1/334 (0.3%)
Haematoma infection	1/334 (0.3%)
Infection	1/334 (0.3%)
Lobar pneumonia	2/334 (0.6%)
Lung abscess	1/334 (0.3%)
Peritonitis	2/334 (0.6%)
Postoperative wound infection	1/334 (0.3%)
Pyelonephritis	1/334 (0.3%)
Respiratory tract infection	1/334 (0.3%)
Sepsis	7/334 (2.1%)
Septic shock	4/334 (1.2%)
Streptococcal sepsis	1/334 (0.3%)
Urinary tract infection	5/334 (1.5%)
Urosepsis	3/334 (0.9%)
Wound infection	1/334 (0.3%)
Pneumonia	22/334 (6.6%)
Injury, poisoning and procedural complications
Abdominal wound dehiscence	1/334 (0.3%)
Fractured sacrum	1/334 (0.3%)
Humerus fracture	1/334 (0.3%)
Inadequate analgesia	1/334 (0.3%)
Incisional hernia, obstructive	1/334 (0.3%)
Lumbar vertebral fracture	1/334 (0.3%)
Meniscus lesion	1/334 (0.3%)
Pneumothorax traumatic	1/334 (0.3%)
Post procedural haemorrhage	2/334 (0.6%)
Procedural complication	1/334 (0.3%)
Subdural haematoma	1/334 (0.3%)
Traumatic haematoma	1/334 (0.3%)
Investigations
Haemoglobin decreased	3/334 (0.9%)
Staphylococcus test positive	1/334 (0.3%)
Weight decreased	1/334 (0.3%)
Metabolism and nutrition disorders
Dehydration	2/334 (0.6%)
Diabetic ketoacidosis	1/334 (0.3%)
Failure to thrive	2/334 (0.6%)
Hypercalcaemia	2/334 (0.6%)
Hyperglycaemic hyperosmolar nonketotic syndrome	1/334 (0.3%)
Hyperkalaemia	3/334 (0.9%)
Hyperphosphataemia	1/334 (0.3%)
Hypocalcaemia	1/334 (0.3%)
Hypokalaemia	1/334 (0.3%)
Hypomagnesaemia	1/334 (0.3%)
Hyponatraemia	3/334 (0.9%)
Hypovolaemia	1/334 (0.3%)
Malnutrition	1/334 (0.3%)
Tumour lysis syndrome	1/334 (0.3%)
Type 2 diabetes mellitus	1/334 (0.3%)
Musculoskeletal and connective tissue disorders
Back pain	3/334 (0.9%)
Lumbar spinal stenosis	1/334 (0.3%)
Musculoskeletal chest pain	1/334 (0.3%)
Osteolysis	1/334 (0.3%)
Pain in extremity	2/334 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/334 (0.3%)
Adrenocortical carcinoma	1/334 (0.3%)
Bile duct cancer	2/334 (0.6%)
Brain neoplasm	1/334 (0.3%)
Brain neoplasm malignant	1/334 (0.3%)
Bronchioloalveolar carcinoma	1/334 (0.3%)
Cancer pain	2/334 (0.6%)
Cervix cancer metastatic	1/334 (0.3%)
Cervix carcinoma	2/334 (0.6%)
Colon cancer metastatic	1/334 (0.3%)
Endometrial cancer metastatic	1/334 (0.3%)
Gastric cancer	1/334 (0.3%)
Glioblastoma	4/334 (1.2%)
Glioblastoma multiforme	1/334 (0.3%)
Intracranial tumour haemorrhage	1/334 (0.3%)
Liposarcoma	1/334 (0.3%)
Lung cancer metastatic	2/334 (0.6%)
Lung neoplasm malignant	6/334 (1.8%)
Malignant neoplasm progression	4/334 (1.2%)
Malignant ovarian cyst	1/334 (0.3%)
Malignant pleural effusion	1/334 (0.3%)
Mantle cell lymphoma	1/334 (0.3%)
Metastases to central nervous system	4/334 (1.2%)
Metastatic carcinoma of the bladder	1/334 (0.3%)
Metastatic pain	1/334 (0.3%)
Neoplasm	1/334 (0.3%)
Non-Hodgkin's lymphoma recurrent	1/334 (0.3%)
Non-small cell lung cancer	2/334 (0.6%)
Non-small cell lung cancer metastatic	1/334 (0.3%)
Non-small cell lung cancer stage IV	1/334 (0.3%)
Oesophageal adenocarcinoma	1/334 (0.3%)
Oesophageal carcinoma	3/334 (0.9%)
Oncologic complication	2/334 (0.6%)
Ovarian cancer	4/334 (1.2%)
Pancreatic carcinoma	8/334 (2.4%)
Pancreatic carcinoma metastatic	3/334 (0.9%)
Prostate cancer metastatic	1/334 (0.3%)
Rectal cancer	1/334 (0.3%)
Rectal cancer metastatic	2/334 (0.6%)
Renal cell carcinoma	1/334 (0.3%)
Sarcoma	1/334 (0.3%)
Small cell lung cancer stage unspecified	3/334 (0.9%)
Small intestine carcinoma metastatic	1/334 (0.3%)
Squamous cell carcinoma of the cervix	1/334 (0.3%)
T-cell lymphoma recurrent	1/334 (0.3%)
Tumour haemorrhage	1/334 (0.3%)
Tumour invasion	1/334 (0.3%)
Tumour necrosis	1/334 (0.3%)
Uterine cancer	1/334 (0.3%)
Uterine leiomyosarcoma	1/334 (0.3%)
Vulval cancer	1/334 (0.3%)
Nervous system disorders
Brain oedema	1/334 (0.3%)
Cerebrovascular accident	3/334 (0.9%)
Embolic cerebral infarction	1/334 (0.3%)
Haemorrhage intracranial	2/334 (0.6%)
Haemorrhagic stroke	1/334 (0.3%)
Headache	1/334 (0.3%)
Hemiparesis	1/334 (0.3%)
Neuralgia	1/334 (0.3%)
Normal pressure hydrocephalus	1/334 (0.3%)
Paraplegia	1/334 (0.3%)
Stupor	1/334 (0.3%)
Syncope	1/334 (0.3%)
Thrombotic stroke	1/334 (0.3%)
Transient ischaemic attack	1/334 (0.3%)
Psychiatric disorders
Delirium	1/334 (0.3%)
Depression	1/334 (0.3%)
Mental disorder	1/334 (0.3%)
Mental status changes	4/334 (1.2%)
Substance-induced psychotic disorder	1/334 (0.3%)
Renal and urinary disorders
Calculus bladder	1/334 (0.3%)
Haematuria	4/334 (1.2%)
Postrenal failure	1/334 (0.3%)
Renal failure	5/334 (1.5%)
Renal failure acute	4/334 (1.2%)
Renal impairment	1/334 (0.3%)
Reproductive system and breast disorders
Ovarian mass	1/334 (0.3%)
Vaginal haemorrhage	2/334 (0.6%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/334 (0.3%)
Chronic obstructive pulmonary disease	2/334 (0.6%)
Dyspnoea	3/334 (0.9%)
Emphysema	1/334 (0.3%)
Epistaxis	2/334 (0.6%)
Hiccups	1/334 (0.3%)
Hypoxia	1/334 (0.3%)
Lung infiltration	1/334 (0.3%)
Painful respiration	1/334 (0.3%)
Pleural effusion	10/334 (3%)
Pleuritic pain	1/334 (0.3%)
Pneumonia aspiration	2/334 (0.6%)
Pneumothorax	1/334 (0.3%)
Pulmonary embolism	20/334 (6%)
Respiratory failure	3/334 (0.9%)
Stridor	1/334 (0.3%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/334 (0.3%)
Urticaria	1/334 (0.3%)
Vascular disorders
Deep vein thrombosis	8/334 (2.4%)
Embolism venous	2/334 (0.6%)
Hypertension	1/334 (0.3%)
Hypotension	4/334 (1.2%)
Jugular vein thrombosis	1/334 (0.3%)
Subclavian artery stenosis	1/334 (0.3%)
Other (Not Including Serious) Adverse Events
	Dalteparin Sodium
	Affected / at Risk (%)	# Events
Total	328/334 (98.2%)
Blood and lymphatic system disorders
Anemia	54/334 (16.2%)
Thrombocytopenia	42/334 (12.6%)
Neutropenia	27/334 (8.1%)
Cardiac disorders
Tachycardia	18/334 (5.4%)
Gastrointestinal disorders
Nausea	81/334 (24.3%)
Constipation	71/334 (21.3%)
Diarrhea	60/334 (18%)
Vomiting	42/334 (12.6%)
Abdominal pain	41/334 (12.3%)
Ascites	22/334 (6.6%)
General disorders
Injection site hematoma	91/334 (27.2%)
Fatigue	90/334 (26.9%)
Odema peripheral	80/334 (24%)
Disease progression	37/334 (11.1%)
Pyrexia	24/334 (7.2%)
Asthenia	19/334 (5.7%)
Injection site hemorrhage	17/334 (5.1%)
Infections and infestations
Pneumonia	34/334 (10.2%)
Urinary tract infection	32/334 (9.6%)
Upper respiratory tract infection	22/334 (6.6%)
Cellulitis	19/334 (5.7%)
Injury, poisoning and procedural complications
Contusion	52/334 (15.6%)
Investigations
Weight decreased	36/334 (10.8%)
Hemoglobin decreased	17/334 (5.1%)
Metabolism and nutrition disorders
Decreased appetite	48/334 (14.4%)
Hypokalemia	36/334 (10.8%)
Dehydration	24/334 (7.2%)
Hyponatremia	20/334 (6%)
Musculoskeletal and connective tissue disorders
Back pain	45/334 (13.5%)
Pain in extremity	33/334 (9.9%)
Arthralgia	24/334 (7.2%)
Muscle spasms	17/334 (5.1%)
Nervous system disorders
Headache	33/334 (9.9%)
Dizziness	27/334 (8.1%)
Neuropathy peripheral	22/334 (6.6%)
Psychiatric disorders
Anxiety	27/334 (8.1%)
Insomnia	27/334 (8.1%)
Renal and urinary disorders
Hematuria	22/334 (6.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	52/334 (15.6%)
Cough	36/334 (10.8%)
Epistaxis	34/334 (10.2%)
Pleural effusion	31/334 (9.3%)
Pulmonary embolism	24/334 (7.2%)
Skin and subcutaneous tissue disorders
Alopecia	22/334 (6.6%)
Rash	22/334 (6.6%)
Dry skin	18/334 (5.4%)
Ecchymosis	18/334 (5.4%)
Vascular disorders
Hypotension	23/334 (6.9%)

Limitations/Caveats

[Not Specified]

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.