Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00445328
• Collaborator: (none)
• Enrollment: 84
• Locations: 7
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 12
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of dalteparin vs unfractionated heparin for the prevention of VTE (Venous Thromboembolism) in hospitalized acutely ill medical patients.

Condition or Disease	Intervention/Treatment	Phase
Venous Thromboembolism	Drug: Dalteparin (Fragmin); Drug: Unfractionated heparin	Phase 4

Detailed Description

The study was prematurely discontinued due to delay in overall study start-up and inability to meet pre-defined protocol recruitment milestones on June 30th, 2008. There were no safety concerns regarding the study in the decision to terminate the trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prospective Randomized Phase IV Open Label Comparative Study Of Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients.
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: B	Drug: Unfractionated heparin; Unfractionated heparin 5000 IU thrice daily subcutaneously for 6-14 days.
Experimental: A	Drug: Dalteparin (Fragmin); Dalteparin 5000 IU once daily subcutaneously for 6-14 days.

Outcome Measures

Primary Outcome Measures

1. Confirmed Thromboembolic Events [Day 21]

   Confirmed thromboembolic events = 'present' if any following events are present/abnormal, otherwise = 'absent': Deep vein thrombosis measured by Color Doppler ultrasonography lower limbs; pulmonary embolism by chest xray, ventilation-perfusion scan, computed tomography pulmonary angiography; Sudden Death within 24 hours of venous thromboembolism symptoms.

2. Composite of Objectively Verified Thromboembolic Events [Day 21]

   Subjects with objectively verified thromboembolic events: symptomatic proximal and distal deep vein thrombosis [DVT], asymptomatic proximal DVT, fatal or symptomatic non-fatal pulmonary embolism [PE] or sudden death within 24 hours of onset of venous thromboembolism (VTE) symptoms. Occurrence of any ='Present', otherwise = 'Absent'.

Secondary Outcome Measures

1. All Cause Mortality [Day 14, Day 21 (End of Study)]

   Subjects with death from any cause: end of study.

2. Stroke - Ischemic or Hemorrhagic [Day 21]

   Subjects with stroke (either ischemic or hemorrhagic) based on results of CT (computed tomographic) pulmonary angiography

3. Bleeding - Major or Minor [Day 21]

   Subjects with bleeding. Bleeding classified as major if it is: intraocular, spinal/epidural, intracranial or retroperitoneal; or if hemoglobin decreased by ≥ 2 g/dl(grams/deciliter); or if transfusion of ≥ 2 Units of blood or if significant medical or surgical intervention was required; or if it results in death. All other bleeding is classified as minor.

4. Allergic Reactions (Drug-related) [Day 21]

   Subjects with drug-related allergic reactions

5. Thrombocytopenia [Day 21]

   Subjects with thrombocytopenia (low platelets).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Aged greater than or equal to 18 years

• Acute medical condition with a projected hospitalization of greater than or equal to 4 days and had less than or equal to 3 days of prior immobilization for more than two thirds of the day

• Acute congestive heart failure Class III-IV per NHYA/ Acute respiratory failure not requiring mechanical ventilation or Both

• Acute infection without septic shock/ Acute episode of inflammatory bowel disease/ Acute rheumatologic disorders/ Acute lumbar pain or sciatica or vertebral compression with at least one risk factor for VTE

Exclusion Criteria:

• Contraindications to use of anticoagulants

• Active bleeding or abnormal coagulation tests

• Recent (less than 1 month) head injury, hemorrhagic stroke, cerebral tumor or intracranial aneurysm or ischemic stroke within the last month.

• Major surgical or invasive procedure within the last month resulting in ongoing convalescence

• Lumbar or spinal puncture within last 48 hours

• S creatinine levels more than 2

• On inotropic agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Hyderabad	Andhra Pradesh	India	500 068
2	Pfizer Investigational Site	Ahmedabad	Gujarat	India	380 054
3	Pfizer Investigational Site	Trichur	Kerala	India	680 005
4	Pfizer Investigational Site	Indore	Madhya Pradesh	India	452001
5	Pfizer Investigational Site	Chennai	Tamil Nadu	India	600 006
6	Pfizer Investigational Site	Kolkata	West Bengal	India	700 029
7	Pfizer Investigational Site	Kolkata	West Bengal	India	700 054

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.

• ClinicalTrials.gov Identifier: NCT00445328
• Other Study ID Numbers: A6301080
• First Posted: Mar 8, 2007
• Last Update Posted: Oct 15, 2009
• Last Verified: Oct 1, 2009

• Keywords provided by , ,: hospitalised acutely medically ill patients; Venous Thromboembolism, Infection, Inflammatory Bowel Diseases, Heart Failure, Congestive, Sciatica
• Additional relevant MeSH terms: Thromboembolism; Venous Thromboembolism; Heparin; Calcium heparin; Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight

Study Results

Participant Flow

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU (International Units) dalteparin in 0.2 mL (milliliters) subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Period Title: Overall Study
STARTED	42	42
Received Treatment	41	42
COMPLETED	39	36
NOT COMPLETED	3	6

Baseline Characteristics

Arm/Group Title	Dalteparin	Unfractionated Heparin	Total
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.	Total of all reporting groups
Overall Participants	41	42	83
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.7 (10.6)	60.8 (10.9)	61.3 (10.7)
Sex: Female, Male (Count of Participants)
Female	18 43.9%	21 50%	39 47%
Male	23 56.1%	21 50%	44 53%

Outcome Measures

1. Primary Outcome

Title	Confirmed Thromboembolic Events
Description	Confirmed thromboembolic events = 'present' if any following events are present/abnormal, otherwise = 'absent': Deep vein thrombosis measured by Color Doppler ultrasonography lower limbs; pulmonary embolism by chest xray, ventilation-perfusion scan, computed tomography pulmonary angiography; Sudden Death within 24 hours of venous thromboembolism symptoms.
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) set: all subjects who were randomized, received at least 1 dose of study drug and had undergone at least 1 test of primary efficacy assessment.

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Measure Participants	37	35
Present	0 0%	0 0%
Absent	37 90.2%	35 83.3%

2. Secondary Outcome

Title	All Cause Mortality
Description	Subjects with death from any cause: end of study.
Time Frame	Day 14, Day 21 (End of Study)

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT)

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Measure Participants	37	37
Number [participants]	0 0%	1 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dalteparin, Unfractionated Heparin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	P-value is based on chi-square test with alpha as 0.01.
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Stroke - Ischemic or Hemorrhagic
Description	Subjects with stroke (either ischemic or hemorrhagic) based on results of CT (computed tomographic) pulmonary angiography
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT)

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Measure Participants	37	37
Number [participants]	0 0%	0 0%

4. Secondary Outcome

Title	Bleeding - Major or Minor
Description	Subjects with bleeding. Bleeding classified as major if it is: intraocular, spinal/epidural, intracranial or retroperitoneal; or if hemoglobin decreased by ≥ 2 g/dl(grams/deciliter); or if transfusion of ≥ 2 Units of blood or if significant medical or surgical intervention was required; or if it results in death. All other bleeding is classified as minor.
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT)

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Measure Participants	37	37
Major Bleeding	0 0%	1 2.4%
Minor Bleeding	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dalteparin, Unfractionated Heparin
	Comments	Major Bleeding
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Allergic Reactions (Drug-related)
Description	Subjects with drug-related allergic reactions
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT)

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Measure Participants	37	37
Number [participants]	0 0%	0 0%

6. Primary Outcome

Title	Composite of Objectively Verified Thromboembolic Events
Description	Subjects with objectively verified thromboembolic events: symptomatic proximal and distal deep vein thrombosis [DVT], asymptomatic proximal DVT, fatal or symptomatic non-fatal pulmonary embolism [PE] or sudden death within 24 hours of onset of venous thromboembolism (VTE) symptoms. Occurrence of any ='Present', otherwise = 'Absent'.
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT)

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Measure Participants	37	35
Symptomatic DVT Present	0 0%	0 0%
Symptomatic DVT Absent	37 90.2%	35 83.3%
Symptomatic Proximal DVT Present	0 0%	0 0%
Symptomatic Proximal DVT Absent	37 90.2%	35 83.3%
Symptomatic Distal DVT Present	0 0%	0 0%
Symptomatic Distal DVT Absent	37 90.2%	35 83.3%
Asymptomatic Proximal DVT Present	0 0%	0 0%
Asymptomatic Proximal DVT Absent	37 90.2%	35 83.3%
Fatal pulmonary embolism Present	0 0%	0 0%
Fatal pulmonary embolism Absent	37 90.2%	35 83.3%
Symptomatic non-fatal pulmonary embolism Present	0 0%	0 0%
Symptomatic non-fatal pulmonary embolism Absent	37 90.2%	35 83.3%
Sudden Death within 24 hours of VTE Present	0 0%	0 0%
Sudden Death within 24 hours of VTE Absent	37 90.2%	35 83.3%

7. Secondary Outcome

Title	Thrombocytopenia
Description	Subjects with thrombocytopenia (low platelets).
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT)

Arm/Group Title	Dalteparin	Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)	5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
Measure Participants	37	37
Number [participants]	35 85.4%	31 73.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dalteparin, Unfractionated Heparin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1355
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Arm/Group Title	Dalteparin		Unfractionated Heparin
Arm/Group Description	5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A)		5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days.
All Cause Mortality
	Dalteparin		Unfractionated Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dalteparin		Unfractionated Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/ (NaN)		4/ (NaN)
Gastrointestinal disorders
Diarrhoea	1/41 (2.4%)		0/42 (0%)
General disorders
Chest pain	0/41 (0%)		1/42 (2.4%)
Injection site rash	0/41 (0%)		1/42 (2.4%)
Infections and infestations
Lobar pneumonia	1/41 (2.4%)		0/42 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/41 (0%)		2/42 (4.8%)
Skin and subcutaneous tissue disorders
Drug eruption	0/41 (0%)		1/42 (2.4%)
Surgical and medical procedures
Hysterosalpingo-oophorectomy	0/41 (0%)		1/42 (2.4%)
Other (Not Including Serious) Adverse Events
	Dalteparin		Unfractionated Heparin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/ (NaN)		7/ (NaN)
Gastrointestinal disorders
Constipation	0/41 (0%)		2/42 (4.8%)
Vomiting	0/41 (0%)		2/42 (4.8%)
General disorders
Pyrexia	4/41 (9.8%)		2/42 (4.8%)
Investigations
Blood pressure increased	2/41 (4.9%)		1/42 (2.4%)
Haemoglobin decreased	2/41 (4.9%)		1/42 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/41 (2.4%)		2/42 (4.8%)

Limitations/Caveats

Study terminated prematurely due to delay in overall study start-up and inability to meet predefined protocol recruitment milestones; sample size too small to permit meaningful statistical analyses. No statistical analyses for all but 2 endpoints.

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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.