Study of Octaplex (Human Prothrombin Complex Concentrate)... | NCT00618098

Label	Type	Description	Intervention Names
Octaplex (human prothrombin complex concentrate)	Experimental	Participants to receive1 or more Octaplex infusions intravenously until their International Normalized Ratio (INR) was < 1.5.	Biological: Octaplex (human prothrombin complex concentrate)
Fresh frozen plasma	Active Comparator	Participants to receive1 or more fresh frozen plasma infusions intravenously until their International Normalized Ratio (INR) was < 1.5.	Biological: Fresh frozen plasma

Name	Type	Description	Arm Group Labels	Other Names
Octaplex (human prothrombin complex concentrate)	Biological	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.).

Measure	Description	Time Frame
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	15 minutes after the end of first infusion of OCTAPLEX or FFP
RBC Transfusion Units	Total number of intra-operative units of red blood cell (RBC) given to patients	Intra-operative; throughout the duration of operation

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Wolfgang Frenzel, MD	International Medical Director	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Contact Octapharma for Facility details		Philadelphia	Pennsylvania	19141	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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.).
BG001	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00097 BG001103 BG002200

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Posted

Count of Participants

Participants

15 minutes after the end of first infusion of OCTAPLEX or FFP

ID	Title	Description
OG000	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.).
OG001	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.

Units	Counts
Participants	OG00097 OG001103

Title

Denominators

Categories

Title	Measurements
	OG00074 OG00131

Primary

RBC Transfusion Units

Total number of intra-operative units of red blood cell (RBC) given to patients

Posted

Mean

Standard Deviation

mL of RBC Transfusion During Surgery

Intra-operative; throughout the duration of operation

ID	Title	Description
OG000	Octaplex (Human Prothrombin Complex Concentrate)(Pre-interim Analysis)	Participants to receive1 or more Octaplex infusions intravenously until their International Normalized Ratio (INR) was < 1.5 and had surgery prior to interim analysis 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.).
OG001	Fresh Frozen Plasma (Prior to Interim Analysis)	Participants to receive1 or more fresh frozen plasma infusions intravenously until their International Normalized Ratio (INR) was < 1.5 and required surgery prior to interim analysis 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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.).	19	97	27	97	57	97
EG001	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.	13	103	28	103	58	103

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0010 events0 affected103 at risk
Hemmorhagic Anemia	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Bradycardia	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Cardiac Failute	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Cardiac Failure Acute	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0012 events2 affected103 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Cardiogenic Shock	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Coronary Artery Disease	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Right Ventricular Failure	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0011 events1 affected103 at risk
Supraventricular Tachycardia	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Condition Aggravated	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Multi-organ failure	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0010 events0 affected103 at risk
Cardiac Valve Abscess	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Diverticulitis	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Endocarditis, Bacterial	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Gangrene	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Pneumonia	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0013 events3 affected103 at risk
Sepsis	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0010 events0 affected103 at risk
Drug Toxicity	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Gastrointestinal Stoma Complication	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Medical Device Complication	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Postoperative Respiratory Distress	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Procedural Pain	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Thrombosis in Device	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Vascular Pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Brain Compression	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Acute Respiratory Distress Syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0011 events1 affected103 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Hemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0002 events2 affected97 at risk EG0010 events0 affected103 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Pulmonary Edema	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Respiratory Arrest	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected103 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0012 events2 affected103 at risk
Cardiovascular Insufficiency	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk
Hypotension	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 events0 affected97 at risk EG0012 events2 affected103 at risk
Thrombosis	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected103 at risk

ID	Term
D025861	Blood Coagulation Disorders, Inherited
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D020147	Coagulation Protein Disorders
D006474	Hemorrhagic Disorders
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D040181	Genetic Diseases, X-Linked

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0007 events7 affected97 at risk EG0015 events5 affected103 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0004 events4 affected97 at risk EG0017 events7 affected103 at risk
Nausea	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0009 events9 affected97 at risk EG00113 events13 affected103 at risk
Pyrexia	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0004 events4 affected97 at risk EG0017 events7 affected103 at risk
Pneumonia	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0004 events4 affected97 at risk EG0017 events7 affected103 at risk
Procedural Pain	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0009 events9 affected97 at risk EG0012 events2 affected103 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0008 events8 affected97 at risk EG0016 events6 affected103 at risk
Hypotension	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG00012 events12 affected97 at risk EG00111 events11 affected103 at risk