Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Comp... | NCT00708435

ID	Type	Description	Link
1462	Other Identifier	CSL Behring
2007-007861-19	EudraCT Number

Label	Type	Description	Intervention Names
Beriplex® P/N	Experimental		Biological: Beriplex® P/N (Kcentra)
Fresh frozen plasma	Active Comparator		Biological: Fresh frozen plasma

Name	Type	Description	Arm Group Labels	Other Names
Beriplex® P/N (Kcentra)	Biological	Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight	Beriplex® P/N

Measure	Description	Time Frame
Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed	Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 1 and 4 hours after the end of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".	At 1 and 4 hours after the end of infusion
Percentage of Participants Who Had a Rapid Decrease of the International Normalized Ratio (INR)	A rapid decrease of the international normalized ratio (INR) was defined as an INR ≤ 1.3 at 30 minutes after the end of the infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy.	30 minutes after end of infusion

Measure	Description	Time Frame
Percentage of Participants Who Had Hemostatic Efficacy for Visible or Non-visible Musculoskeletal Bleeding	Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 3 and 6 hours after the start of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female subjects ≥ 18 years
Subjects who have received oral vitamin K-antagonist therapy
Subjects who have acute major bleeding, defined as one of the following: life-threatening or potentially life-threatening, acute bleeding associated with a fall in hemoglobin (Hb) level ≥ 2g/dL, bleeding requiring blood product transfusion
INR ≥ 2 within 3 hours before start of study treatment
Informed consent has been obtained

Exclusion Criteria:

Expected survival of less than 3 days, or expected surgery in less than 1 day
Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control the acute bleeding event
Use of unfractionated or low molecular weight heparin use from 24 hours prior to enrollment or expected need within 24 hours after start of infusion
For patients with ICH: Glasgow coma score (GCS) < 7; intracerebral hematoma volume > 30cc as assessed by ABC/21; for subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm; for subarachnoid hemorrhage: any evidence of hydrocephalus; infratentorial ICH location; epidural hematomas; intraventricular extension of hemorrhage; modified Rankin score (mRS) of >3 prior to ICH
History of thrombotic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within 3 months of enrollment
Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies
Suspected or confirmed sepsis at time of enrollment
Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study
Large blood vessel rupture (e.g. in advanced cancer patient)
Pre-existing progressive fatal disease with a life expectancy of less than 2 months
Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia
Treatment with any other investigational medicinal product within 30 days prior to inclusion into the study
Presence or history of hypersensitivity to components of the study medication
Pregnant or breast-feeding women
Prior inclusion in this study or any other CSL Behring-sponsored Beriplex study

Name	Affiliation	Role
Program Director, Clinical R&D	CSL Behring	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Study Site		Birmingham	Alabama	35248-3280	United States
Study Site

PubMed Identifier	Type	Citation	Retractions
23935011	Result	Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013 Sep 10;128(11):1234-43. doi: 10.1161/CIRCULATIONAHA.113.002283. Epub 2013 Aug 9.

ID	Title	Description
FG000	Beriplex® P/N	Beriplex® P/N : Single intravenous infusion as required to treat acute major bleeding; dosage 25, 35 or 50 units/kg depending on baseline INR, amount of coagulation factor IX and body weight.
FG001	Fresh Frozen Plasma

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

Percentage of Participants Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed

Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 1 and 4 hours after the end of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

The Intention-to-Treat Efficacy (ITT-E) population included all randomized participants who had received any study product, presented with acute major bleeding, and had an international normalized ratio (INR) > 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.

Posted

Number

95% Confidence Interval

percentage of participants

At 1 and 4 hours after the end of infusion

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma: Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants	OG00098 OG001104

Title

Denominators

Categories

Title	Measurements
	OG00072.4(63.6 to 81.3) OG00165.4(56.2 to 74.5)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The analysis of hemostatic efficacy was via calculation of the 95% confidence interval (CI) for the difference (Beriplex minus plasma) in the percentage of participants with effective hemostasis.	95% confidence interval	Farrington and Manning's method was used to estimate the 95% CI for the difference in the percentage of participants with hemostasis.		Both primary endpoints had to be non-inferior for Beriplex to be non-inferior. No P-value is entered as non-inferiority was assessed via the 95% CI calculation for the difference (Beriplex minus plasma) in the % of subjects with effective hemostasis.	Difference in effective hemostasis (%)	7.1			2-Sided	95	-5.8	19.9

Primary

Percentage of Participants Who Had a Rapid Decrease of the International Normalized Ratio (INR)

A rapid decrease of the international normalized ratio (INR) was defined as an INR ≤ 1.3 at 30 minutes after the end of the infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy.

The ITT-E population included all randomized participants who had received any study product, presented with acute major bleeding, and had an INR > 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.

Posted

Number

95% Confidence Interval

percentage of participants

30 minutes after end of infusion

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma: Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants

Secondary

Percentage of Participants Who Had Hemostatic Efficacy for Visible or Non-visible Musculoskeletal Bleeding

Hemostatic efficacy was determined by a blinded independent board as excellent, good, or poor/none, based on prespecified definitions. Assessments of visible or non-visible musculoskeletal bleeding were made at 3 and 6 hours after the start of infusion. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' was a hemostatic efficacy rating of "poor/none".

Posted

Number

95% Confidence Interval

percentage of participants

At 3 and 6 hours after the start of infusion

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma: Intravenous Infusion, dosage depending on baseline INR and body weight

Secondary

Incremental in Vivo Recovery (IVR) (Response) of Factors II, VII, IX, and X, Protein C, and Protein S for Beriplex

The incremental IVR [(IU/dL)/(IU/kg)] was calculated as follows: (IU/dL activity rise in plasma)/(IU/kg body weight infused) = [maximum increase in component plasma level within 3 hours compared to pre-infusion (IU/dL)]/{[exact dose of component in drug administered (IU)]/[body weight (kg)]}.

Posted

Mean

Standard Deviation

(IU/dL)/(IU/kg body weight)

Before infusion and up to 3 h after the start of infusion

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N : Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight

Units	Counts
Participants	OG000

Secondary

Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S

Plasma levels are presented as the percentage of normal at pre-infusion and 30 min and 24 h after the start of infusion. The plasma level assay results are reported as a potency relative to a standard, where 100% is considered to be normal.

Posted

Mean

Standard Deviation

percentage of normal

From preinfusion until 24 h after the start of infusion

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N : Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma : Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants

Secondary

Percentage of Participants With INR Correction at Various Times After the Start of Infusion

The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.

Posted

Number

percentage of participants

From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N : Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma : Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants

Secondary

Percentage of Participants With INR Correction at Various Times After Randomization

The time taken from randomization to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization.

Posted

Number

percentage of participants

From randomization until INR correction; calculated at 2.5, 3, 5, 8, 14, and 26 h after randomization.

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N : Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma : Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants

Secondary

Transfusion of Red Blood Cells

Red blood cells were packed red blood cells (PRBCs).

Posted

Mean

Standard Deviation

Units of PRBCs

From the start of infusion until 24 h after the start of infusion

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma: Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants	OG000

Secondary

Use of Other Blood Products and Hemostatic Agents

Other blood products and hemostatic agents containing coagulation factors (such as whole blood, plasma, albumin, platelets) not including PRBCs.

Posted

Mean

Standard Deviation

Units of blood products

From the start of infusion until 24 h after the start of infusion

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma: Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants	OG000

Secondary

45-Day All-cause Mortality

Posted

Number

participants

Until Day 45

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma: Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts
Participants	OG000

Secondary

Overall Treatment-emergent Adverse Events (TEAEs)

Number of participants with TEAEs. Treatment-related AEs were defined as events whose relationship to study treatment was definitely related, probably related, or possibly related in the opinion of the investigator. AEs with missing relationship were considered related to treatment. Serious TEAEs were treatment-emergent SAEs. Deaths reported up to and including Day 45; one additional Beriplex death occurred after Day 45.

The ITT-S population included all participants who were randomized and who had received any portion of study product. Participants in the ITT-S population were analyzed 'as treated'.

Posted

Number

participants

From the start of infusion up to the allowed time window of the Day 10 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs.

ID	Title	Description
OG000	Beriplex® P/N	Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
OG001	Fresh Frozen Plasma	Fresh frozen plasma: Intravenous Infusion, dosage depending on baseline INR and body weight

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial flutter	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0010 events0 affected109 at risk
Cardiac failure	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0011 events1 affected109 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0012 events2 affected109 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0012 events1 affected109 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0010 events0 affected109 at risk
Encephalopathy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0012 events2 affected109 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0010 events0 affected109 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0012 events2 affected109 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Convulsion	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0011 events1 affected109 at risk
Bacteraemia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Cellulitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Gastroenteritis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Septic shock	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0011 events1 affected109 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0011 events1 affected109 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0011 events1 affected109 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Lung carcinoma cell type unspecified stage iv	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Oesophageal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0002 events1 affected103 at risk EG0010 events0 affected109 at risk
Haematoma	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0012 events2 affected109 at risk
Haemorrhagic anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Liver disorder	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Device dislocation	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0011 events1 affected109 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0011 events1 affected109 at risk
Sudden death	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0010 events0 affected109 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0015 events4 affected109 at risk
Myocardial infarction	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0011 events1 affected109 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Oedema peripheral	General disorders	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected103 at risk EG0017 events7 affected109 at risk
Pyrexia	General disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected103 at risk EG0014 events4 affected109 at risk
Chest pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0013 events3 affected109 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00010 events10 affected103 at risk EG0014 events4 affected109 at risk
Dizziness	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected103 at risk EG0010 events0 affected109 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events2 affected103 at risk EG0014 events4 affected109 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected103 at risk EG0010 events0 affected109 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0013 events3 affected109 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected103 at risk EG0018 events8 affected109 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0014 events4 affected109 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0013 events3 affected109 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0012 events2 affected109 at risk
Tachycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected103 at risk EG0011 events1 affected109 at risk
Bradycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0010 events0 affected109 at risk
International normalised ratio increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0010 events0 affected109 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0016 events6 affected109 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0013 events3 affected109 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected103 at risk EG0013 events3 affected109 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0010 events0 affected109 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected103 at risk EG0013 events3 affected109 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0010 events0 affected109 at risk
Insomnia	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected103 at risk EG0013 events3 affected109 at risk
Anxiety	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected103 at risk EG0012 events2 affected109 at risk
Agitation	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0011 events1 affected109 at risk
Mental status change	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0010 events0 affected109 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0013 events3 affected109 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected103 at risk EG0011 events1 affected109 at risk
Hypotension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected103 at risk EG0014 events3 affected109 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected103 at risk EG0013 events3 affected109 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected103 at risk EG0010 events0 affected109 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected103 at risk EG0010 events0 affected109 at risk

ID	Term
D001778	Blood Coagulation Disorders
D020141	Hemostatic Disorders

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D006474	Hemorrhagic Disorders

ID	Title	Description
BG000	Beriplex® P/N	Beriplex® P/N : Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight
BG001	Fresh Frozen Plasma	Fresh frozen plasma : Intravenous Infusion, dosage depending on baseline INR and body weight
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Beriplex® P/N	Beriplex® P/N : Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight			32	103	46	103
EG001	Fresh Frozen Plasma	Fresh frozen plasma : Intravenous Infusion, dosage depending on baseline INR and body weight			26	109	40	109