Deep Vein Thrombosis
Conditions
Keywords
Acute, symptomatic and objectively confirmed DVT
Brief summary
The objective of the study is to compare the safety of innohep® and Unfractionated Heparin (UFH) in terms of clinically relevant bleedings in elderly patients with impaired renal function for initial treatment of acute Deep Venous Thrombosis (DVT). The primary response criterion is the percentage of patients with clinically relevant bleeding events prior to day 90 +/- 5.
Interventions
DRUGinnohep®
175 anti-Xa IU/kg administered subcutaneously (SC) once daily
DRUGHeparin
Heparin 50 IU /kg followed by a total dose of 400 to 600 IU/kg/day divided into two SC injections daily.
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a symptomatic and objectively confirmed Venous Thromboembolism (VTE) (lower limb deep venous thrombosis (DVT) or pulmonary embolus (PE)) with mandatory presences of objectively confirmed and treatment requiring DVT, i.e. symptomatic and objectively confirmed distal DVT or objectively confirmed, symptomatic or asymptomatic proximal DVT (confirmation of DVT should be performed by ultrasonography or venography within 48 hous prior to randomisation) * Patients with an indication for DVT treatment with SC Low Molecular Weight Heparin (LMWH) or Unfractionated Heparin (UFH) followed by Oral Anticoagulant (OAC) for at least 90 days * Hospitalized patients who, during SC anticoagulant treatment, will be followed, as specified in the protocol, on a daily basis either in the hospital or in an out-patient setting * Patients at or above 75 years with a creatinine clearance less than or equal to 60 mL/min calculated according to the Cockcroft-Gault formula * Patients at or above 70 years with a creatinine clearance less than or equal to 30 mL/min calculated according to the Cockcroft-Gault formula
Exclusion criteria
* Patients receiving high dose (i.e. equivalent to a dose recommended for treatment of DVT) of UFH or LMWH or thrombolytic agents within the last 4 weeks except for UFH/LMWH during the last 36 hours prior to randomisation * Patients on oral anticoagulant treatment (vitamin K-antagonists) at or within last 1 week prior to randomisation * Patients with a symptomatic venous thromboembolism (VTE) requiring thrombolytic therapy or invasive intervention * End stage renal disease patients requiring dialysis * Surgery within 2 weeks prior to randomisation or planned surgery, epidural anaesthesia and/or spinal anaesthesia during the SC anticoagulant treatment period * Planned use of acetylsalicylic acid in doses above 300 mg/day, NSAID or Dextran 40 at randomisation and during the SC anticoagulant treatment period * Patients with a current overt bleeding or known haemorrhage condition (e.g. active G.I. ulcer) * Patients with a platelet count \< 100 x 10 9/L * Patients with a known history of heparin-induced thrombocytopenia * Patients with known severe hepatic insufficiency manifested as international normalized ratio (INR) greater than or equal to 1.5 * Patients with uncontrolled severe hypertension i.e. a systolic blood pressure \> 220 mm Hg or diastolic blood pressure \> 120 mm Hg during at least 2 measurements within 24 hours prior to randomisation * Patients with ischaemic stroke at or within last 1 week prior to randomisation * Patients with a known haemorrhagic stroke within 3 months prior to randomisation * Patients with known bacterial endocarditis within 3 months prior to randomisation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients With Clinically Relevant Bleeding Events | prior to day 90 +/- 5 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Patients With Recurrence of Venous Thromboembolism | prior to day 90 +/- 5 |
| Number of Patients With Major Bleeding Events | prior to day 90 +/- 5 |
Countries
Bulgaria, Croatia, Czechia, France, Germany, Poland, Romania, Serbia, Spain
Participant flow
Recruitment details
Recruitment took place between Dec 2005 and May 2008
Pre-assignment details
2 patients were not randomized
Participants by arm
| Arm | Count |
|---|---|
| Innohep® innohep® 175 anti-Xa IU/kg once daily | 269 |
| Heparin Heparin 50 IU /kg followed by a total dose of 400 to 600 IU/kg/day divided into two SC injections daily. | 270 |
| Total | 539 |
Baseline characteristics
| Characteristic | Innohep® | Heparin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 269 Participants | 270 Participants | 539 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 82.9 years STANDARD_DEVIATION 5.7 | 82.6 years STANDARD_DEVIATION 5.8 | 82.8 years STANDARD_DEVIATION 5.7 |
| Region of Enrollment Belgium | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Croatia | 9 participants | 16 participants | 25 participants |
| Region of Enrollment France | 139 participants | 139 participants | 278 participants |
| Region of Enrollment Germany | 10 participants | 10 participants | 20 participants |
| Region of Enrollment Poland | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Romania | 30 participants | 20 participants | 50 participants |
| Region of Enrollment Serbia | 37 participants | 43 participants | 80 participants |
| Region of Enrollment Spain | 39 participants | 38 participants | 77 participants |
| Sex: Female, Male Female | 177 Participants | 168 Participants | 345 Participants |
| Sex: Female, Male Male | 92 Participants | 102 Participants | 194 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 270 | 72 / 264 |
| serious Total, serious adverse events | 63 / 270 | 52 / 264 |
Outcome results
Primary
Number of Patients With Clinically Relevant Bleeding Events
Time frame: prior to day 90 +/- 5
Population: 2 patients randomised to the Heparin group withdrew their consent just after randomisation and before taking any study treatment. No data were collected after visit 1, and due to the nature of the withdrawal, no further information was possible to collect. These patients were excluded from all analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Innohep® | Number of Patients With Clinically Relevant Bleeding Events | 32 Patients |
| Heparin | Number of Patients With Clinically Relevant Bleeding Events | 32 Patients |
Secondary
Number of Patients With Major Bleeding Events
Time frame: prior to day 90 +/- 5
Population: 2 patients randomised to the Heparin group withdrew their consent just after randomisation and before taking any study treatment. No data were collected after visit 1, and due to the nature of the withdrawal, no further information was possible to collect. These patients were excluded from all analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Innohep® | Number of Patients With Major Bleeding Events | 12 Patients |
| Heparin | Number of Patients With Major Bleeding Events | 10 Patients |
Secondary
Number of Patients With Recurrence of Venous Thromboembolism
Time frame: prior to day 90 +/- 5
Population: 2 patients randomised to the Heparin group withdrew their consent just after randomisation and before taking any study treatment. No data were collected after visit 1, and due to the nature of the withdrawal, no further information was possible to collect. These patients were excluded from all analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Innohep® | Number of Patients With Recurrence of Venous Thromboembolism | 16 Patients |
| Heparin | Number of Patients With Recurrence of Venous Thromboembolism | 9 Patients |