Study of Octaplex, a Four-factor Prothrombin Complex Conc... | NCT02740335

NCT02740335

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Octaplex	Experimental	Participants to receive1 Octaplex infusion intravenously	Drug: Octaplex
Beriplex P/N (Kcentra)	Active Comparator	Participants to receive1 Kcentra infusions intravenously	Drug: Beriplex P/N (Kcentra)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Octaplex	Drug	OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).	Octaplex

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Hemostatic Efficacy Rating by IEAB	Hemostatic Efficacy rated by the Independent Endpoint Adjudication Committee based on a 1 to 4 point hemostatic efficacy scale, taking into account blood loss and transfusion requirements in the context of the surgery. Hemostatic efficacy was assessed based on objective criteria in the categories 'excellent', 'good', 'moderate', or 'none'. Ratings of 'excellent' and 'good' were considered as 'effective' hemostasis, while ratings of 'moderate' and 'none' were considered as 'ineffective' hemostasis.	At the end of the surgery
Dichotomous Hemostasis Success	To demostrate clinical non-inferiority of treatment with Octaplex to treatment with Beriplex P/N (Kcentra) with respect to hemostatic success. Effective hemostatis includes Excellent and Good ratings, while Ineffective hemostasis includes Moderate, None and missing ratings from Global hemostatic efficacy observed by IEAB	At the end of surgery

Secondary Outcomes

Measure	Description	Time Frame
Measuring of International Normalized Ratio (INR) to ≤ 1.5	Number of patients with an international normalized ratio (INR) value of less or equal to 1.5 at 30 min (± 15 min) after the end of infusion.	30 minutes after the end of infusion
Coagulation Factor II Levels

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Male or female patients at least 18 years of age.
Patients currently on oral anticoagulation treatment with VKA of coumadin or warfarin type.
Patients being admitted to the hospital or currently hospitalized where:
- an urgent surgery carrying significant bleeding risk (≥50 mL expected blood loss) is required as part of routine clinical care;
- the use of oral or parenteral vitamin K alone to reverse anticoagulation is deemed too slow or inappropriate for reversal;
Patients with an international normalized ratio (INR) of 2.0 or above at the time of decision to reverse the anticoagulation status.
Patients who have given written informed consent and who are able and willing to comply with the procedures described in the study protocol.

Exclusion Criteria

Patients with a life expectancy of less than 48 hours per physician's judgment (e.g. patients with a Glasgow Coma Scale equal to 3 or a Head Abbreviated Injury Score of 6, patients requiring continuous inotropic or pressor support, and patients whose status is post cardiac arrest).
Patients for whom the planned surgery or procedure is commonly associated with a very low bleeding risk (e.g. catheter placement, gastroscopy).
Patients with a history of thromboembolic events (TEEs), myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebrovascular accident, transient ischemic attack, severe peripheral vascular disease, or disseminated intravascular coagulation within 3 months of enrollment.
Patients with a known congenital bleeding disorder.
Patients with a known antiphospholipid antibody syndrome.
Patients with present or past specific factor inhibitor activity.
Patients with thrombocytopenia of <80,000/μL or history of heparin-induced thrombocytopenia.
Patients who have received heparin of any type or any non-VKA anticoagulant within 24 hours prior to enrollment into the study or with potential need to receive these medications before completion of hemostasis evaluation at the end of surgery.
Patients who have received prothrombin complex concentrates (PCCs), fresh frozen plasma or vitamin K within 72 hours prior to enrollment into the study.
Patients with a known history of hypersensitivity to plasma-derived products.
Patients with acute major bleeding or polytrauma.
Pregnant or nursing women.
Patients participating in another interventional clinical study currently or during the past 30 days prior to enrollment into this study.
Patients previously enrolled in this study.

Name	Affiliation	Role
Wolfgang Frenzel	International Medical Monitor	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Octapharma Research Site		Aurora	Colorado	80045	United States
Octapharma Research Site

References Module

Citations

PubMed Identifier	Type	Citation
16810012	Background	American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006 Jul;105(1):198-208. doi: 10.1097/00000542-200607000-00030. No abstract available.
	Background	Campbell P, Roberts G, Eaton V. Managing warfarin therapy in the community. Aust Prescriber 2001; 24:86-89.
	Background	Cushman M, et al. Clinical Practice Guide on Antithrombotic Drug Dosing and Management of Antithrombotic Drug-Associated Bleeding Complications in Adults, American Society of Hematology, 2014.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
FG001	Beriplex P/N (Kcentra)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 19, 2018	Sep 15, 2022

Arm/Group Information

ID	Title	Description
BG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
BG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Full Range

Years

Title

Denominators

Categories

Title	Measurements
	BG00065.6(31 to 90) BG00166.8(32 to 92) BG00266.2(31 to 92)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00047 BG00143 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Pre-Infusion Anticoagulation Therapy

Number

participants

Title

Denominators

Categories

Sol. Fraxiparine (nadroparin calcium)

Title	Measurements
	BG0001 BG0010 BG002

History of TEE

Number

participants

Title

Denominators

Categories

Presence of Embolic or Thrombotic Event

Title	Measurements
	BG00013 BG00118 BG002

Type of Surgey

Number

participants

Title

Denominators

Categories

Cardiothoracic Surgery

Title	Measurements
	BG0005 BG0014 BG002

Estimated Average Blood Loss

Expected average blood loss in mL during surgery for non-anticoagulated patients undergoing the same type of surgical procedure

Number

participants

Title

Denominators

Categories

≥200 mL

Title	Measurements
	BG00055 BG00150

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

Hemostatic Efficacy Rating by IEAB

Hemostatic Efficacy rated by the Independent Endpoint Adjudication Committee based on a 1 to 4 point hemostatic efficacy scale, taking into account blood loss and transfusion requirements in the context of the surgery. Hemostatic efficacy was assessed based on objective criteria in the categories 'excellent', 'good', 'moderate', or 'none'. Ratings of 'excellent' and 'good' were considered as 'effective' hemostasis, while ratings of 'moderate' and 'none' were considered as 'ineffective' hemostasis.

Posted

Count of Participants

Participants

At the end of the surgery

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units	Counts
Participants	OG000105 OG001103

Title

Denominators

Categories

Excellent - 4

Title	Measurements
	OG00041 OG00150

Good - 3

Title	Measurements
	OG000

Primary

Dichotomous Hemostasis Success

To demostrate clinical non-inferiority of treatment with Octaplex to treatment with Beriplex P/N (Kcentra) with respect to hemostatic success. Effective hemostatis includes Excellent and Good ratings, while Ineffective hemostasis includes Moderate, None and missing ratings from Global hemostatic efficacy observed by IEAB

Posted

Count of Participants

Participants

At the end of surgery

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units	Counts
Participants

Secondary

Measuring of International Normalized Ratio (INR) to ≤ 1.5

Number of patients with an international normalized ratio (INR) value of less or equal to 1.5 at 30 min (± 15 min) after the end of infusion.

Posted

Count of Participants

Participants

30 minutes after the end of infusion

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units	Counts
Participants	OG000

Secondary

Coagulation Factor II Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor II

The Hodges-Lehmann Estimator is a method of robust estimation. This estimator is used to give an estimate of the difference between the values in two sets of data. If the two sets of data contain m and n data points respectively, m × n pairs of points (one from each set) can be formed and each pair gives a difference of values. The Hodges-Lehmann estimator for the difference is defined as the median of the m × n differences.

Posted

Mean

95% Confidence Interval

mg/dL

30 minutes after the end of infusion

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units	Counts

Secondary

Coagulation Factor VII Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor VII

Posted

Mean

95% Confidence Interval

mg/dL

30 minutes after the end of infusion

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units

Secondary

Coagulation Factor IX Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor II Factor IX

Posted

Mean

95% Confidence Interval

m/dL

30 minutes after the end of infusion

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units

Secondary

Coagulation Factor X Levels

Change in coagulation factor levels from baseline to after the end of infusion using the Hodges-Lehmann Estimator for median differences: o Factor X

Posted

Mean

95% Confidence Interval

mg/dL

30 minutes after the end of infusion

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units	Counts

Secondary

Number of Patients Requiring Red Blood Cells (RBC)

Number of patients receiving red blood cells (RBC) during the surgery

Posted

Count of Participants

Participants

At the end of surgery

ID	Title	Description
OG000	Octaplex	Participants to receive1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
OG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).

Units	Counts
Participants	OG000

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	Participants to receive 1 Octaplex infusion intravenously Octaplex: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).	5	105	13	105	86	105
EG001	Beriplex P/N (Kcentra)	Participants to receive 1 Kcentra infusion intravenously Beriplex P/N (Kcentra): Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).	1	103	6	103	80	103

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina Unstable	Cardiac disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Cardiac Failure Chronic	Cardiac disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Myocardial Ischaemia	Cardiac disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Haemorrhagic Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Cardiac Failure Acute	Cardiac disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Pneumonia	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Gastritis Erosive	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Mesenteric Haematoma	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Proctitis	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Gastritis Haemorrhagic	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Ileus	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Death	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Multiple Organ Dysfunction Syndrome	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Orchitis	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Anastomotic Haemmorhage	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Failure to Anastomose	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Joint Dislocation	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Subdural Haemorrhage	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Postoperative Wound Complication	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Soft Tissue Haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Ovarian Cancer Stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk
Cerebral Infarction	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Pulmonary Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Shock	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0010 events0 affected103 at risk
Shock Haemorrhagic	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0011 events1 affected103 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0006 events6 affected105 at risk EG0016 events6 affected103 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0003 events3 affected105 at risk EG0015 events5 affected103 at risk
Abdominal Distension	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected105 at risk EG0013 events3 affected103 at risk
Dyschezia	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0013 events3 affected103 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0013 events3 affected103 at risk
Cardiac AEs	Cardiac disorders	MedDRA (19.1)	Non-systematic Assessment	EG0005 events5 affected105 at risk EG0017 events7 affected103 at risk
Asthenia	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG00013 events13 affected105 at risk EG00118 events18 affected103 at risk
Catheter Site Related Reaction	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0004 events4 affected105 at risk EG0012 events2 affected103 at risk
Hyperthermia	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0003 events3 affected105 at risk EG0012 events2 affected103 at risk
Pyrexia	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0013 events3 affected103 at risk
Pneumonia	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0013 events3 affected103 at risk
Procedural Pain	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG00050 events50 affected105 at risk EG00150 events50 affected103 at risk
Postoperative Wound Complications	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG00015 events15 affected105 at risk EG00115 events15 affected103 at risk
Procedural Vomiting	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0004 events4 affected105 at risk EG0010 events0 affected103 at risk
Suture Related Complication	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected105 at risk EG0014 events4 affected103 at risk
Blood Pressure Increase	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0015 events5 affected103 at risk
Body Temperature Increase	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0014 events4 affected103 at risk
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0005 events5 affected105 at risk EG0011 events1 affected103 at risk
Metabolism and nutrition disorders	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0004 events4 affected105 at risk EG0017 events7 affected103 at risk
Nervous System Disorders	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0006 events6 affected105 at risk EG0011 events1 affected103 at risk
Dysuria	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0005 events5 affected105 at risk EG0012 events2 affected103 at risk
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected105 at risk EG0015 events5 affected103 at risk
Vascular Disorders	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected105 at risk EG0016 events6 affected103 at risk
Hypotension	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected105 at risk EG0013 events3 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

ID	Term
D004792	Enzyme Precursors
D045762	Enzymes and Coenzymes
D001779	Blood Coagulation Factors
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D011498	Protein Precursors
D001685	Biological Factors

ID	Term
C025667	prothrombin complex concentrates
D005164	Factor IX
C525441	factor IX, factor VII, factor X, prothrombin drug combination