Angina, Unstable, Myocardial Infarction
Conditions
Keywords
Non-ST Elevation Acute Coronary Syndromes coronary interventions
Brief summary
To compare efficacy and safety of dalteparin compared to unfractionated heparin in patients of non ST elevation acute coronary syndromes who are planned to undergo coronary interventions (angioplasty or bypass surgery)
Detailed description
The study was prematurely discontinued on November 30, 2008 due to delay in meeting pre-defined protocol recruitment milestones. There were no safety concerns regarding the study in the decision to terminate the trial.
Interventions
DRUGDalteparin ( Fragmin)
Dalteparin will be administered at a dose of 120 IU/kg (international units per kilogram) total body weight subcutaneously (SC) every 12 hours up to a maximum dose of 10,000 IU/12 hours.
DRUGUnfractionated heparin
Unfractionated heparin will be given intravenously according to a weight-adjusted nomogram (bolus of 60 U/kg \[units per kilogram\] and initial infusion of 12 U/kg/h \[units per kilogram per hour\]).
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients more than 18 years * Ischemic pain of more than 10 minutes within 24 hours before enrollment * At least two of the following three risk factors : Age more than 60 years ( or more than 50 in case of diabetics), Raised cardiac enzyme levels, abnormal ECG findings
Exclusion criteria
* Contraindications to use of anticoagulants * Active bleeding or abnormal coagulation tests * Ischemic stroke within last 6 months or hemorrhagic stroke * Lumbar or spinal puncture within last 48 hours * S creatinine levels more than 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30 | Baseline to Day 30 | Death or non-fatal myocardial infarction (MI) after receiving 48 hours of study medication (event date - first dose date) on or before day 30 from baseline. Death: fatal event resulting from any cause. New MI: electrocardiographic (ECG) and or biomarker criteria of myocardial necrosis. Biochemical markers: creatine phosphokinase - myocardial band (CPK-MB) levels and the qualitative troponin-T test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Stroke | End of hospitalization, Day 30 | Stroke: a sudden, focal neurologic deficit that is not reversible within 24 hours and is not the result of any readily identifiable cause (e.g., tumor or trauma). |
| Number of Subjects With Recurrent Angina With or Without Need for Hospitalization and or Revascularization | End of hospitalization, Day 30 | Recurrent angina: angina at rest lasting at least five minutes that was associated with a new ST-segment shift (elevation or depression) of more than 0.1 millivolt (mV), or with T-wave inversions, in two contiguous electrocardiographic leads; angina without electrocardiographic changes that prompted a decision to perform a revascularization procedure; or angina after hospital discharge that resulted in rehospitalization. |
| Number of Subjects With Death or Non-fatal Myocardial Infarction (MI), Computed Separately, at End of Hospitalization and 30 Days | End of hospitalization, Day 30 | Death or non-fatal myocardial infarction (MI) after receiving 48 hours of study medication (event date - first dose date) at end of hospitalization and on Day 30. Death: fatal event resulting from any cause. New MI: defined by electrocardiographic and/or biomarker criteria of myocardial necrosis. Biochemical markers: creatine phosphokinase - myocardial band (CPK-MB) levels and the qualitative troponin-T test. |
| Number of Subjects With Stent Thrombosis and Abrupt Closures During Hospitalization | End of hospitalization, Day 30 | Abrupt vessel closure and or stent thrombosis: occurrence of vessel closure (no visible antegrade flow of contrast dye occurring after balloon angioplasty) or stent thrombosis determined angiographically. |
| Number of Subjects With Bleeding by Thrombolysis in Myocardial Infarction (TIMI) Criteria | End of hospitalization, Day 30 | Thrombolysis in myocardial infarction (TIMI) major bleeding: at least a 5-grams per deciliter (g/dL) decrease in hemoglobin, at least a 15 percent (%) decrease in hematocrit, or intracranial bleeding. TIMI minor bleeding: associated with gastrointestinal or genitourinary bleeding, with an absolute decrease in hemoglobin of 4 g/dL or more, or decrease in hematocrit of at least 12%. |
Countries
India
Participant flow
Recruitment details
Subjects participated in the study between 22 June 2007 and 30 December 2008.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Dalteparin 120 international units per kilogram (IU/kg) total body weight subcutaneously (SC) every 12 hours up to a maximum dose of 10,000 IU/12 hours; given for a minimum of 48 hours and until no further anticoagulation is required, and at least through angiography and percutaneous coronary intervention (PCI), if performed. | 88 |
| Arm B: Unfractioned Heparin (UFH) Weight-adjusted nomogram (bolus of 60 units per kilogram \[U/kg\] and initial infusion of 12 units per kilogram per hour \[U/kg/h\]); given for a minimum of 48 hours and until no further anticoagulation is required, and at least through angiography and percutaneous coronary intervention (PCI), if performed. | 83 |
| Total | 171 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Death | 3 | 4 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Other | 5 | 2 |
| Overall Study | Received Drug in Other Treatment Group | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
| Overall Study | Withdrawal by Subject Prior to Treatment | 0 | 2 |
Baseline characteristics
| Characteristic | Arm A: Dalteparin | Arm B: Unfractioned Heparin (UFH) | Total |
|---|---|---|---|
| Age, Customized 18 - 44 years | 6 participants | 5 participants | 11 participants |
| Age, Customized 45 - 64 years | 36 participants | 40 participants | 76 participants |
| Age, Customized >=65 years | 46 participants | 38 participants | 84 participants |
| Sex: Female, Male Female | 29 Participants | 40 Participants | 69 Participants |
| Sex: Female, Male Male | 59 Participants | 43 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 88 | 59 / 83 |
| serious Total, serious adverse events | 4 / 88 | 13 / 83 |
Outcome results
Primary
Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30
Death or non-fatal myocardial infarction (MI) after receiving 48 hours of study medication (event date - first dose date) on or before day 30 from baseline. Death: fatal event resulting from any cause. New MI: electrocardiographic (ECG) and or biomarker criteria of myocardial necrosis. Biochemical markers: creatine phosphokinase - myocardial band (CPK-MB) levels and the qualitative troponin-T test.
Time frame: Baseline to Day 30
Population: Evaluable population: all subjects who took study medication for at least 48 hours from baseline and had complete information on the endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Dalteparin | Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30 | Death | 2 participants |
| Arm A: Dalteparin | Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30 | Non-fatal Myocardial Infarction | 2 participants |
| Arm A: Dalteparin | Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30 | Death or Non-fatal Myocardial Infarction | 4 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30 | Death | 4 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30 | Non-fatal Myocardial Infarction | 1 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Death or Non-fatal Myocardial Infarction Through and Up to Day 30 | Death or Non-fatal Myocardial Infarction | 5 participants |
Comparison: Death after receiving 48 hours of study medication (Event date - First dose date) and on or before day 30 from baseline. Difference in proportion (Dalteparin-UFH)(%).95% CI: [-8.59, 3.4]upper limit of 95% CI <= 10%
Comparison: Non-fatal Myocardial Infarction after receiving 48 hours of study medication (Event date - First dose date) and on or before day 30 from baseline. Difference in proportion (Dalteparin-UFH)(%).95% CI: [-3.02, 5.52]upper limit of 95% CI <= 10%
Comparison: Death or Non-fatal Myocardial Infarction after receiving 48 hours of study medication (Event date - First dose date) and on or before day 30 from baseline. Difference in proportion (Dalteparin-UFH)(%).95% CI: [-8.62, 5.93]upper limit of 95% CI <= 10%
Secondary
Number of Subjects With Bleeding by Thrombolysis in Myocardial Infarction (TIMI) Criteria
Thrombolysis in myocardial infarction (TIMI) major bleeding: at least a 5-grams per deciliter (g/dL) decrease in hemoglobin, at least a 15 percent (%) decrease in hematocrit, or intracranial bleeding. TIMI minor bleeding: associated with gastrointestinal or genitourinary bleeding, with an absolute decrease in hemoglobin of 4 g/dL or more, or decrease in hematocrit of at least 12%.
Time frame: End of hospitalization, Day 30
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Dalteparin | Number of Subjects With Bleeding by Thrombolysis in Myocardial Infarction (TIMI) Criteria | 0 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Bleeding by Thrombolysis in Myocardial Infarction (TIMI) Criteria | 0 participants |
Secondary
Number of Subjects With Death or Non-fatal Myocardial Infarction (MI), Computed Separately, at End of Hospitalization and 30 Days
Death or non-fatal myocardial infarction (MI) after receiving 48 hours of study medication (event date - first dose date) at end of hospitalization and on Day 30. Death: fatal event resulting from any cause. New MI: defined by electrocardiographic and/or biomarker criteria of myocardial necrosis. Biochemical markers: creatine phosphokinase - myocardial band (CPK-MB) levels and the qualitative troponin-T test.
Time frame: End of hospitalization, Day 30
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Dalteparin | Number of Subjects With Death or Non-fatal Myocardial Infarction (MI), Computed Separately, at End of Hospitalization and 30 Days | 3 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Death or Non-fatal Myocardial Infarction (MI), Computed Separately, at End of Hospitalization and 30 Days | 3 participants |
Comparison: Difference in proportion (Dalteparin-UFH)(%).p-value: 195% CI: [-6.05, 5.95]Chi-squared
Secondary
Number of Subjects With Recurrent Angina With or Without Need for Hospitalization and or Revascularization
Recurrent angina: angina at rest lasting at least five minutes that was associated with a new ST-segment shift (elevation or depression) of more than 0.1 millivolt (mV), or with T-wave inversions, in two contiguous electrocardiographic leads; angina without electrocardiographic changes that prompted a decision to perform a revascularization procedure; or angina after hospital discharge that resulted in rehospitalization.
Time frame: End of hospitalization, Day 30
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Dalteparin | Number of Subjects With Recurrent Angina With or Without Need for Hospitalization and or Revascularization | 3 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Recurrent Angina With or Without Need for Hospitalization and or Revascularization | 3 participants |
Comparison: Difference in proportion (Dalteparin-UFH)(%).p-value: 195% CI: [-6.05, 5.95]Chi-squared
Secondary
Number of Subjects With Stent Thrombosis and Abrupt Closures During Hospitalization
Abrupt vessel closure and or stent thrombosis: occurrence of vessel closure (no visible antegrade flow of contrast dye occurring after balloon angioplasty) or stent thrombosis determined angiographically.
Time frame: End of hospitalization, Day 30
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Dalteparin | Number of Subjects With Stent Thrombosis and Abrupt Closures During Hospitalization | 0 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Stent Thrombosis and Abrupt Closures During Hospitalization | 0 participants |
Secondary
Number of Subjects With Stroke
Stroke: a sudden, focal neurologic deficit that is not reversible within 24 hours and is not the result of any readily identifiable cause (e.g., tumor or trauma).
Time frame: End of hospitalization, Day 30
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Dalteparin | Number of Subjects With Stroke | 1 participants |
| Arm B: Unfractioned Heparin (UFH) | Number of Subjects With Stroke | 0 participants |
Comparison: Difference in proportion (Dalteparin-UFH)(%).p-value: 195% CI: [-1.2, 3.73]Chi-squared