Venous Thromboembolism
Conditions
Keywords
observational prolonged thromboprophylaxis
Brief summary
The objective of this study is to observe the safety, tolerability, and compliance in the use of Fragmin® for prolonged thromboprophylaxis in post-surgery high-risk orthopedic patients.
Detailed description
All patients prescribed Fragmin® (Dalteparin Sodium) for prolonged thromboprophylaxis will be eligible for study
Interventions
DRUGFragmin® (Dalteparin Sodium)
Administered per prescribing physician
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patient, undergoing major orthopedic surgery * At least 18 years old
Exclusion criteria
* Hypersensitivity to Fragmin or other low molecular weight heparins or unfractioned heparin; * History of heparin induced thrombocytopaenia type II * Acute gastroduodenal ulcer, cerebral haemorrhage, or other active haemorrhage. * Serious coagulation disorder; * Septic endocarditis; * Injuries to and operations in the central nervous system, eye and ear within one month before orthopaedic surgery; * Spinal or epidural anesthesia or other procedures requiring spinal puncture and concomitant treatment with high doses of dalteparin (such as those needed to treat acute deep vein thrombosis, pulmonary embolism, and Unstable coronary artery disease); * Patients with serum creatinine level \> 150 umol/l; * Platelet count of less than 100 000 per cubic millimeter at the beginning of the therapy; * High probability that patient will not return to the centre for follow-up; * Patient on oral anticoagulation therapy in the last 7 days; * Ongoing anticoagulant therapy with other medications or non-pharmacologic therapy during the study period; * Weight less than 40 kg; * Simultaneous participation in another pharmacological study or receiving any investigational drug 30 days or less before surgery; * Pregnancy or breastfeeding; * Clinically significant hepatic dysfunction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Assessment of Efficacy of Treatment | Baseline up to Week 5 | Efficacy of treatment as assessed by physician was evaluated on the 5 point categorical scale: excellent, very good, good, fair, poor. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Risk Factors | Baseline | Risk factors evaluated for vascular thromboembolism (VTE) were age (above 40 years, but age was not a strong risk factor as a prediction of potential VTE episode), gender (primarily females but males after 65 years also influenced VTE episode), obesity, pregnancy, liver disease, kidney disease, hormone therapy, immobilization, previous surgery, concomitant malignant disease, positive family history, varicose veins, smoking, chemotherapy, catheter in vein, Heart Failure III New York Heart Association (NYHA) and Heart Failure IV NYHA. |
| Number of Participants With Thromboembolism | Baseline up to Week 5 | Thromboembolism is the formation of blood clot in the blood vessels due to an embolus (a detached intravascular mass capable of clogging arterial capillary beds at a site far from its origin). |
| Number of Participants With Bleeding | Baseline up to Week 5 | Major bleeding: defined as fatal bleeding, clinically overt bleeding causing a fall in hemoglobin more than or equal to 20 gram/litre (g/L) (2 g/decilitre \[dL\]), clinically overt bleeding leading to transfusion of more than or equal to 2 units of whole blood or red cells, or symptomatic bleeding in areas of special concern (intracranial, retroperitoneal, intraocular, intraspinal, pericardial, intramuscular with compartmental syndrome, or intraarticular). Minor bleeding was defined as bleeding that did not meet the definition of major bleeding. |
| Participant's Global Evaluation of Treatment | Baseline up to Week 5 | Participant's global evaluation of treatment for overall response and comfort was evaluated on the four point categorical scale: excellent, good, fair and poor. |
| Participant's Dosage Regimen | Baseline up to Week 5 | Approved dosage regimens for Fragmin in major orthopedic surgery included; (1): first dose of Fragmin 5000 IU in the evening before the day of surgery, followed by daily doses of 5000 IU up to 5 weeks; (2): first dose of Fragmin 2500 IU 2 hours before surgery, and a second dose of 2500 IU 8 to 12 hours later, not earlier than 4 hours after surgery, followed by daily doses of 5000 IU up to 5 weeks or (3): first dose of Fragmin 2500 IU 4 to 8 hours postoperatively, followed by daily doses of 5000 IU up to 5 weeks. |
| Administration Schedule of Treatment | Baseline up to Week 5 | Administration schedule for Fragmin in major orthopedic surgery Included was categorized as; (1): first dose of Fragmin 5000 IU in the evening before the day of surgery, followed by daily doses of 5000 IU up to 5 weeks; (2): first dose of Fragmin 2500 IU 2 hours before surgery, and a second dose of 2500 IU 8 to 12 hours later, not earlier than 4 hours after surgery, followed by daily doses of 5000 IU up to 5 weeks or (3): first dose of Fragmin 2500 IU 4 to 8 hours postoperatively, followed by daily doses of 5000 IU up to 5 weeks. |
| Number of Participants Compliant With the Treatment | Baseline up to Week 5 | Compliance was defined as participants documented with Dalteparin Sodium up to 5 weeks after initiation of thromboprophylaxis. |
| Number of Participants With Hematoma | Baseline up to Week 5 | Hematoma is a localized collection of blood outside of a blood vessel. It includes subcutaneous hematoma and injection-site hematoma. |
| Physician's Assessment of Tolerability of Treatment | Baseline up to Week 5 | Tolerability of treatment as assessed by physician was evaluated on the five point categorical scale: excellent, very good, good, fair, poor. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalteparin Sodium Dalteparin Sodium (Fragmin) 2500 IU/0.2 mL and 5000 IU/2 mL s.c as per registered indications for 5 weeks. | 503 |
| Total | 503 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Lost to Follow-up | 16 |
| Overall Study | Other | 5 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Dalteparin Sodium |
|---|---|
| Age Continuous | 63.5 Years STANDARD_DEVIATION 12.6 |
| Concomitant Study Medications | NA Participants |
| Medical history | NA Participants |
| Primary diagnosis | NA Participants |
| Prior Study Medications | NA Participants |
| Prior Surgery History | NA Participants |
| Procedures After Primary Diagnosis | NA Participants |
| Sex: Female, Male Female | 340 Participants |
| Sex: Female, Male Male | 163 Participants |
| Thromboembolic Disease Assessment | NA Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 46 / 503 |
| serious Total, serious adverse events | 26 / 503 |
Outcome results
Primary
Physician's Assessment of Efficacy of Treatment
Efficacy of treatment as assessed by physician was evaluated on the 5 point categorical scale: excellent, very good, good, fair, poor.
Time frame: Baseline up to Week 5
Population: The Full Analysis Set (FAS) included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Physician's Assessment of Efficacy of Treatment | Excellent | 432 Participants |
| Dalteparin Sodium | Physician's Assessment of Efficacy of Treatment | Very good | 44 Participants |
| Dalteparin Sodium | Physician's Assessment of Efficacy of Treatment | Good | 2 Participants |
| Dalteparin Sodium | Physician's Assessment of Efficacy of Treatment | Fair | 2 Participants |
| Dalteparin Sodium | Physician's Assessment of Efficacy of Treatment | Not reported | 22 Participants |
| Dalteparin Sodium | Physician's Assessment of Efficacy of Treatment | Poor | 1 Participants |
Other Pre-specified
Administration Schedule of Treatment
Administration schedule for Fragmin in major orthopedic surgery Included was categorized as; (1): first dose of Fragmin 5000 IU in the evening before the day of surgery, followed by daily doses of 5000 IU up to 5 weeks; (2): first dose of Fragmin 2500 IU 2 hours before surgery, and a second dose of 2500 IU 8 to 12 hours later, not earlier than 4 hours after surgery, followed by daily doses of 5000 IU up to 5 weeks or (3): first dose of Fragmin 2500 IU 4 to 8 hours postoperatively, followed by daily doses of 5000 IU up to 5 weeks.
Time frame: Baseline up to Week 5
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Administration Schedule of Treatment | Administration Schedule 1 | 327 Participants |
| Dalteparin Sodium | Administration Schedule of Treatment | Administration Schedule 2 | 2 Participants |
| Dalteparin Sodium | Administration Schedule of Treatment | Administration Schedule 3 | 115 Participants |
| Dalteparin Sodium | Administration Schedule of Treatment | Other | 59 Participants |
Other Pre-specified
Number of Participants Compliant With the Treatment
Compliance was defined as participants documented with Dalteparin Sodium up to 5 weeks after initiation of thromboprophylaxis.
Time frame: Baseline up to Week 5
Population: Data was collected but not statistically summarized for analysis.
Other Pre-specified
Number of Participants With Bleeding
Major bleeding: defined as fatal bleeding, clinically overt bleeding causing a fall in hemoglobin more than or equal to 20 gram/litre (g/L) (2 g/decilitre \[dL\]), clinically overt bleeding leading to transfusion of more than or equal to 2 units of whole blood or red cells, or symptomatic bleeding in areas of special concern (intracranial, retroperitoneal, intraocular, intraspinal, pericardial, intramuscular with compartmental syndrome, or intraarticular). Minor bleeding was defined as bleeding that did not meet the definition of major bleeding.
Time frame: Baseline up to Week 5
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Bleeding | Major Bleeding | 0 Participants |
| Dalteparin Sodium | Number of Participants With Bleeding | Minor Bleeding | 0 Participants |
Other Pre-specified
Number of Participants With Hematoma
Hematoma is a localized collection of blood outside of a blood vessel. It includes subcutaneous hematoma and injection-site hematoma.
Time frame: Baseline up to Week 5
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin Sodium | Number of Participants With Hematoma | 2 Participants |
Other Pre-specified
Number of Participants With Risk Factors
Risk factors evaluated for vascular thromboembolism (VTE) were age (above 40 years, but age was not a strong risk factor as a prediction of potential VTE episode), gender (primarily females but males after 65 years also influenced VTE episode), obesity, pregnancy, liver disease, kidney disease, hormone therapy, immobilization, previous surgery, concomitant malignant disease, positive family history, varicose veins, smoking, chemotherapy, catheter in vein, Heart Failure III New York Heart Association (NYHA) and Heart Failure IV NYHA.
Time frame: Baseline
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Risk Factors | Age | 353 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Obesity | 205 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Gender | 291 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Pregnancy | 12 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Liver disease | 8 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Kidney disease | 7 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Hormone therapy | 20 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Immobilization | 51 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Previous surgery | 257 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Concomitant malignant disease | 11 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Positive family history | 16 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Varicose veins | 181 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Smoking | 92 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Chemotherapy | 4 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Catheter in vein | 204 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Heart failure III New York Heart Association(NYHA) | 6 Participants |
| Dalteparin Sodium | Number of Participants With Risk Factors | Heart failure IV NYHA | 0 Participants |
Other Pre-specified
Number of Participants With Thromboembolism
Thromboembolism is the formation of blood clot in the blood vessels due to an embolus (a detached intravascular mass capable of clogging arterial capillary beds at a site far from its origin).
Time frame: Baseline up to Week 5
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin Sodium | Number of Participants With Thromboembolism | 3 Participants |
Other Pre-specified
Participant's Dosage Regimen
Approved dosage regimens for Fragmin in major orthopedic surgery included; (1): first dose of Fragmin 5000 IU in the evening before the day of surgery, followed by daily doses of 5000 IU up to 5 weeks; (2): first dose of Fragmin 2500 IU 2 hours before surgery, and a second dose of 2500 IU 8 to 12 hours later, not earlier than 4 hours after surgery, followed by daily doses of 5000 IU up to 5 weeks or (3): first dose of Fragmin 2500 IU 4 to 8 hours postoperatively, followed by daily doses of 5000 IU up to 5 weeks.
Time frame: Baseline up to Week 5
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Participant's Dosage Regimen | Dosage Regimen 1 | 327 Participants |
| Dalteparin Sodium | Participant's Dosage Regimen | Dosage Regimen 2 | 2 Participants |
| Dalteparin Sodium | Participant's Dosage Regimen | Dosage Regimen 3 | 115 Participants |
| Dalteparin Sodium | Participant's Dosage Regimen | Other | 59 Participants |
Other Pre-specified
Participant's Global Evaluation of Treatment
Participant's global evaluation of treatment for overall response and comfort was evaluated on the four point categorical scale: excellent, good, fair and poor.
Time frame: Baseline up to Week 5
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall response (Excellent) | 236 Participants |
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall response (Good) | 220 Participants |
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall response (Fair) | 20 Participants |
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall response (Poor) | 1 Participants |
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall comfort (Excellent) | 129 Participants |
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall comfort (Good) | 238 Participants |
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall comfort (Fair) | 106 Participants |
| Dalteparin Sodium | Participant's Global Evaluation of Treatment | Overall comfort (Poor) | 4 Participants |
Other Pre-specified
Physician's Assessment of Tolerability of Treatment
Tolerability of treatment as assessed by physician was evaluated on the five point categorical scale: excellent, very good, good, fair, poor.
Time frame: Baseline up to Week 5
Population: The Safety Analysis Set included all those participants who received at least 1 dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Physician's Assessment of Tolerability of Treatment | Excellent | 354 Participants |
| Dalteparin Sodium | Physician's Assessment of Tolerability of Treatment | Very good | 116 Participants |
| Dalteparin Sodium | Physician's Assessment of Tolerability of Treatment | Good | 10 Participants |
| Dalteparin Sodium | Physician's Assessment of Tolerability of Treatment | Fair | 0 Participants |
| Dalteparin Sodium | Physician's Assessment of Tolerability of Treatment | Poor | 0 Participants |
| Dalteparin Sodium | Physician's Assessment of Tolerability of Treatment | Not reported | 23 Participants |