Venous Thromboembolism
Conditions
Keywords
hospitalised acutely medically ill patients; Venous Thromboembolism, Infection, Inflammatory Bowel Diseases, Heart Failure, Congestive, Sciatica
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.
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.
Interventions
Dalteparin 5000 IU once daily subcutaneously for 6-14 days.
DRUGUnfractionated heparin
Unfractionated heparin 5000 IU thrice daily subcutaneously for 6-14 days.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| All Cause Mortality | Day 14, Day 21 (End of Study) | Subjects with death from any cause: end of study. |
| Thrombocytopenia | Day 21 | Subjects with thrombocytopenia (low platelets). |
| Allergic Reactions (Drug-related) | Day 21 | Subjects with drug-related allergic reactions |
| Stroke - Ischemic or Hemorrhagic | Day 21 | Subjects with stroke (either ischemic or hemorrhagic) based on results of CT (computed tomographic) pulmonary angiography |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalteparin 5000 IU dalteparin in 0.2 mL subcutaneously once a day (Arm A) | 41 |
| Unfractionated Heparin 5000 IU unfractionated Heparin (UFH) in 5 mL subcutaneously 3 times a day (Arm B) for 6 to 14 days. | 42 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Other | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Dalteparin | Unfractionated Heparin | Total |
|---|---|---|---|
| Age Continuous | 61.7 years STANDARD_DEVIATION 10.6 | 60.8 years STANDARD_DEVIATION 10.9 | 61.3 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 39 Participants |
| Sex: Female, Male Male | 23 Participants | 21 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / — | 7 / — |
| serious Total, serious adverse events | 2 / — | 4 / — |
Outcome results
Primary
Composite of Objectively Verified Thromboembolic Events
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
Population: Intent to treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic DVT Present | 0 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic DVT Absent | 37 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Proximal DVT Present | 0 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Proximal DVT Absent | 37 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Distal DVT Present | 0 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Distal DVT Absent | 37 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Asymptomatic Proximal DVT Present | 0 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Asymptomatic Proximal DVT Absent | 37 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Fatal pulmonary embolism Present | 0 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Fatal pulmonary embolism Absent | 37 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic non-fatal pulmonary embolism Present | 0 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic non-fatal pulmonary embolism Absent | 37 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Sudden Death within 24 hours of VTE Present | 0 participants |
| Dalteparin | Composite of Objectively Verified Thromboembolic Events | Sudden Death within 24 hours of VTE Absent | 37 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic non-fatal pulmonary embolism Present | 0 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic DVT Present | 0 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Asymptomatic Proximal DVT Absent | 35 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic DVT Absent | 35 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Sudden Death within 24 hours of VTE Present | 0 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Proximal DVT Present | 0 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Fatal pulmonary embolism Present | 0 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Proximal DVT Absent | 35 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic non-fatal pulmonary embolism Absent | 35 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Distal DVT Present | 0 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Fatal pulmonary embolism Absent | 35 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Symptomatic Distal DVT Absent | 35 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Sudden Death within 24 hours of VTE Absent | 35 participants |
| Unfractionated Heparin | Composite of Objectively Verified Thromboembolic Events | Asymptomatic Proximal DVT Present | 0 participants |
Primary
Confirmed Thromboembolic Events
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin | Confirmed Thromboembolic Events | Present | 0 participants |
| Dalteparin | Confirmed Thromboembolic Events | Absent | 37 participants |
| Unfractionated Heparin | Confirmed Thromboembolic Events | Present | 0 participants |
| Unfractionated Heparin | Confirmed Thromboembolic Events | Absent | 35 participants |
Secondary
All Cause Mortality
Subjects with death from any cause: end of study.
Time frame: Day 14, Day 21 (End of Study)
Population: Intent to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin | All Cause Mortality | 0 participants |
| Unfractionated Heparin | All Cause Mortality | 1 participants |
p-value: 1Chi-squared
Secondary
Allergic Reactions (Drug-related)
Subjects with drug-related allergic reactions
Time frame: Day 21
Population: Intent to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin | Allergic Reactions (Drug-related) | 0 participants |
| Unfractionated Heparin | Allergic Reactions (Drug-related) | 0 participants |
Secondary
Bleeding - Major or Minor
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
Population: Intent to treat (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin | Bleeding - Major or Minor | Major Bleeding | 0 participants |
| Dalteparin | Bleeding - Major or Minor | Minor Bleeding | 0 participants |
| Unfractionated Heparin | Bleeding - Major or Minor | Major Bleeding | 1 participants |
| Unfractionated Heparin | Bleeding - Major or Minor | Minor Bleeding | 0 participants |
Comparison: Major Bleedingp-value: 1Chi-squared
Secondary
Stroke - Ischemic or Hemorrhagic
Subjects with stroke (either ischemic or hemorrhagic) based on results of CT (computed tomographic) pulmonary angiography
Time frame: Day 21
Population: Intent to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin | Stroke - Ischemic or Hemorrhagic | 0 participants |
| Unfractionated Heparin | Stroke - Ischemic or Hemorrhagic | 0 participants |
Secondary
Thrombocytopenia
Subjects with thrombocytopenia (low platelets).
Time frame: Day 21
Population: Intent to Treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin | Thrombocytopenia | 35 participants |
| Unfractionated Heparin | Thrombocytopenia | 31 participants |
p-value: 0.1355Chi-squared