Reversal of Anticoagulant Treatment
Conditions
Keywords
anticoagulant reversal, urgent surgery, invasive procedures, vitamin K, prothrombin complex concentrate
Brief summary
The purpose of this study is to determine whether Octaplex (human prothrombin complex concentrate) can reverse the effects of anticoagulants when compared to the standard treatment of fresh frozen plasma (FFP).
Detailed description
The primary objective of the study is to demonstrate that the efficacy of Octaplex as a reversal agent in patients under vitamin K antagonist therapy with the need for urgent surgery or invasive procedures was not clinically inferior to that of FFP. The secondary objective of the study is to investigate the safety and tolerability of Octaplex compared to FFP in patients under vitamin K antagonist therapy with the need for urgent surgery or invasive procedures.
Interventions
BIOLOGICALOctaplex (human prothrombin complex concentrate)
INR is determined 15 minutes after the end of each infusion. Each dose (mL/kg body weight) was calculated as = ln(INR/1.4)/0.52. The maximum dose for initial treatment was not to exceed 5500 IU. If the INR is ≥ 1.5 after the initial infusion, additional infusions will be repeated until the INR was \< 1.5. Octaplex (500 units, IU) is supplied in vials and was reconstituted with 20 mL of Water for Injection (Ph.Eur.).
BIOLOGICALFresh frozen plasma
INR is determined 15 minutes after the end of each infusion. The initial dose is 10 mL/kg for a participant with an initial INR of \< 3 and 15 mL/kg for a participant with an initial INR of ≥ 3. If the INR is ≥ 1.5 after the initial infusion, additional infusions of 5 mL/kg will be repeated until the INR was \< 1.5. Fresh frozen plasma is supplied by the blood bank at each study site and will be prepared and handled according to the site's standard practice.
Sponsors
Octapharma
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
* Male or female patients at least 18 years of age. * Patients receiving oral anticoagulation with coumadin or warfarin derived agents. * Patients who have need for urgent surgery or an invasive procedure up to 8 hours after admission or identification of a patient currently hospitalized, where oral or parenteral vitamin K therapy is deemed too slow in its action for reversal of coumadin or warfarin anticoagulant effects. * Patients with an international normalized ratio (INR) of 2.0 or above. * Patients who have given written informed consent or for whom written informed consent has been obtained from the patient's legal representative on their behalf. * Patients able and willing to comply with the procedures laid out in the study protocol. In the case of unconscious and/or incapacitated patients, the willingness of the patient's legal representative for the patient to undergo the procedures laid out in the study protocol.
Exclusion criteria
* Patients with a life expectancy of less than 48 hours (eg, patients with a Glasgow Coma Scale (GCS) equal to 3 or a head abbreviated injury score (AIS) of 6, patients requiring continuous inotropic or pressor support, patients status post-cardiac arrest). * Patients with a history within the last 6 months of disseminated intravascular coagulation (DIC), or hyperfibrinolysis. * Patients with a known congenital coagulation disorder. * Patients with known antiphospholipid antibody syndrome or have known lupus anticoagulant antibodies. * Patients with present or past specific factor inhibitor activity. * Patients with thrombocytopenia of \< 80,000 or a history of heparin induced thrombocytopenia (HIT). * Patients having received heparin of any type or any non-coumadin or warfarin anticoagulant immediately prior and/or intended to be given within the first 1 hour post-infusion. * Patients who have received vitamin K more than 3 hours prior to the infusion of study drug. * Patients with a history of hypersensitivity to plasma-derived products. * Pregnant or nursing women. * Patients participating in another clinical treatment study currently or during the past 1 month prior to study inclusion. * Patients previously enrolled in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| INR Response | 15 minutes after the end of first infusion of OCTAPLEX or FFP | Number of patients who had an INR response, defined as the correction of patient's INR to \<1.5, 15 minutes after the end of first infusion with study medication |
| RBC Transfusion Units | Intra-operative; throughout the duration of operation | Total number of intra-operative units of red blood cell (RBC) given to patients |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Octaplex (Human Prothrombin Complex Concentrate) Participants to receive1 or more Octaplex infusions intravenously until their International Normalized Ratio (INR) was \< 1.5.
Octaplex (human prothrombin complex concentrate): INR is determined 15 minutes after the end of each infusion. Each dose (mL/kg body weight) was calculated as = ln(INR/1.4)/0.52. The maximum dose for initial treatment was not to exceed 5500 IU. If the INR is ≥ 1.5 after the initial infusion, additional infusions will be repeated until the INR was \< 1.5. Octaplex (500 units, IU) is supplied in vials and was reconstituted with 20 mL of Water for Injection (Ph.Eur.). | 97 |
| Fresh Frozen Plasma Participants to receive1 or more fresh frozen plasma infusions intravenously until their International Normalized Ratio (INR) was \< 1.5.
Fresh frozen plasma: INR is determined 15 minutes after the end of each infusion. The initial dose is 10 mL/kg for a participant with an initial INR of \< 3 and 15 mL/kg for a participant with an initial INR of ≥ 3. If the INR is ≥ 1.5 after the initial infusion, additional infusions of 5 mL/kg will be repeated until the INR was \< 1.5. Fresh frozen plasma is supplied by the blood bank at each study site and will be prepared and handled according to the site's standard practice. | 103 |
| Total | 200 |
Baseline characteristics
| Characteristic | Octaplex (Human Prothrombin Complex Concentrate) | Fresh Frozen Plasma | Total |
|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 12.9 | 67.6 years STANDARD_DEVIATION 14.8 | 66.6 years STANDARD_DEVIATION 19.9 |
| Age, Customized 18-60 years | 36 Participants | 30 Participants | 66 Participants |
| Age, Customized 61-74 years | 35 Participants | 34 Participants | 69 Participants |
| Age, Customized ≥75 years | 26 Participants | 39 Participants | 65 Participants |
| Race/Ethnicity, Customized African American | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Caucasian, non-Hispanic | 88 Participants | 96 Participants | 184 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 31 Participants | 32 Participants | 63 Participants |
| Sex: Female, Male Male | 66 Participants | 71 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 97 | 13 / 103 |
| other Total, other adverse events | 57 / 97 | 58 / 103 |
| serious Total, serious adverse events | 27 / 97 | 28 / 103 |
Outcome results
Primary
INR Response
Number of patients who had an INR response, defined as the correction of patient's INR to \<1.5, 15 minutes after the end of first infusion with study medication
Time frame: 15 minutes after the end of first infusion of OCTAPLEX or FFP
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Octaplex (Human Prothrombin Complex Concentrate) | INR Response | 74 Participants |
| Fresh Frozen Plasma | INR Response | 31 Participants |
Primary
RBC Transfusion Units
Total number of intra-operative units of red blood cell (RBC) given to patients
Time frame: Intra-operative; throughout the duration of operation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex (Human Prothrombin Complex Concentrate) | RBC Transfusion Units | 0.4 mL of RBC Transfusion During Surgery | Standard Deviation 2.35 |
| Fresh Frozen Plasma | RBC Transfusion Units | 0.3 mL of RBC Transfusion During Surgery | Standard Deviation 0.77 |
| Octaplex (Human Prothrombin Complex Concentrate)(Post-interim Analysis) | RBC Transfusion Units | 0.2 mL of RBC Transfusion During Surgery | Standard Deviation 0.5 |
| Fresh Frozen Plasma (Post Interim Analysis) | RBC Transfusion Units | 0.0 mL of RBC Transfusion During Surgery | Standard Deviation 0.13 |