Safety and Pregnancy Outcomes in Thrombocythemia Patients... | NCT00567502

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Label	Type	Description	Intervention Names
1		XAGRID® (anagrelide hydrochloride)
2		Xagrid + Other cytoreductive
3		Other cytoreductive

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies	Pre-defined events (PDEs) were evaluated whenever an event occurred and was defined by a panel of independent qualified physicians, blinded to cytoreductive therapy, validated all PDEs prior to analysis (Event Validation Panel). Non-PDE death only included deaths not recorded as outcome of another PDE.	Up to 5 years
Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events	SSAR: serious adverse event (SAE) that was considered related to cytoreductive therapy. SAE: any untoward medical occurrence that at any dose resulted in death, life-threatening (at the time of the event), in-patient hospitalization/prolongation of existing hospitalization (elective hospitalizations/procedures for pre-existing conditions that had not worsened were excluded), resulted in persistent or significant disability/incapacity or congenital abnormality/birth defect. Relatedness (suspected/not suspected) to XAGRID or other cytoreductive theraphy was determined by the investigator. As for SSARs, it was important to consider whether the events were related to XAGRID or other cytoreductive therapy. A participant was included in Xagrid or other treatment group based on treatment exposure, participants received Xagrid + Other was counted both in Xagrid and other treatment group.	Up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Event Rate of Thrombohaemorrhagic Events	Event Rate of Thrombohaemorrhagic Events was calculated by dividing number of participants with events by total patient-year exposure. The reporting unit is per 100 participant-years of treatment exposure. Thrombohaemorrhagic Events is a composite endpoint of the PDEs myocardial infarction, angina, stroke, transient ischaemic attack, venous thromboembolic events, intermittent claudication/digital ischaemia, and major haemorrhagic events.

Eligibility Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinic of Haematology		Limassol		3304	Cyprus
Rigshospitalet

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29079600	Derived	Birgegard G, Besses C, Griesshammer M, Gugliotta L, Harrison CN, Hamdani M, Wu J, Achenbach H, Kiladjian JJ. Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the Evaluation of Anagrelide Efficacy and Long-term Safety study. Haematologica. 2018 Jan;103(1):51-60. doi: 10.3324/haematol.2017.174672. Epub 2017 Oct 27.
24334294

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant Summary of Product Characteristics (SmPC) at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant Summary of Product Characteristics (SmPC) at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion.
BG001	XAGRID+Other (Cytoreductives)	Participants who received XAGRID along with Other cytoreductives drugs at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
BG002	Other (Cytoreductives)	Participants who received other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
BG003	No Essential Thrombocythemia (ET) Therapy	Participants who were not receiving any cytoreductive treatment for at least 28 consecutive days at the time of registering into the study for a 5 year observation period, during which participants were able to switch treatments per investigator's discretion.
BG004	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

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00055.4± 14.99 BG00159.9± 13.74 BG00267.4± 13.05 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Less than (<) 65 years

Title	Measurements
	BG000575 BG00189 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000501 BG00180 BG002

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 With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies

Pre-defined events (PDEs) were evaluated whenever an event occurred and was defined by a panel of independent qualified physicians, blinded to cytoreductive therapy, validated all PDEs prior to analysis (Event Validation Panel). Non-PDE death only included deaths not recorded as outcome of another PDE.

First Treatment Safety Population included participants who received cytoreductive therapy at registration. All events/data were allocated to the treatment that a participant was receiving at the time of the event/assessment.

Posted

Number

percentage of participants

Up to 5 years

ID	Title	Description
OG000	XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period.
OG001	XAGRID+Other (Cytoreductives)	Participants who received XAGRID+Other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
OG002	Other (Cytoreductives)	Participants who received other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.

Units	Counts
Participants	OG000804 OG001141 OG0022666

Title

Denominators

Categories

Myocardial infarction

Title	Measurements
	OG0001.0 OG0010.0 OG0021.5

Angina

Secondary

Event Rate of Thrombohaemorrhagic Events

Event Rate of Thrombohaemorrhagic Events was calculated by dividing number of participants with events by total patient-year exposure. The reporting unit is per 100 participant-years of treatment exposure. Thrombohaemorrhagic Events is a composite endpoint of the PDEs myocardial infarction, angina, stroke, transient ischaemic attack, venous thromboembolic events, intermittent claudication/digital ischaemia, and major haemorrhagic events.

Overall Treatment Safety Population. As participant could switch between therapies a participant with an event could be allocated to more than one therapy group. Participants analyzed included who were exposed to the specific treatment any time during the study.

Posted

Number

participants/100 participant-years

Up to 5 years

ID	Title	Description
OG000	XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period.
OG001	XAGRID+Other (Cytoreductives)	Participants who received XAGRID+Other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.

Secondary

Platelet Count

Overall Treatment Safety population, Here n = participants evaluable at specified time-points. As participant could switch between therapies a participant with an event could be allocated to more than one therapy group. Participants analyzed included who were exposed to the specific treatment any time during the study.

Posted

Mean

Standard Deviation

10^9 per Liter (10^9/L)

Baseline, Month 6,12,18, 24, 30, 36, 42, 48, 54, 60

ID	Title	Description
OG000	XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period.
OG001	XAGRID+Other (Cytoreductives)	Participants who received XAGRID+Other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.
OG002	Other (Cytoreductives)	Participants who received other (Cytoreductives) at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study or after switching from another treatment any time during the 5 year observation period.Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.

Secondary

Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy

Total duration for each participant = sum of [stop date - start date + 1] across all periods of time where the specific treatment was taken during the study, where start date = registration/consent date for treatments started before registration/consent date and/or stop date withdrawal/final date for treatments ongoing at the time of withdrawal/end of study. Where a participant has multiple records of the same therapy on the same day, the therapy is counted once for that day.

Posted

Mean

Standard Deviation

days

Up to 5 years

ID	Title	Description
OG000	XAGRID Taken	Participants who received XAGRID from "Xagrid only" or "Xagrid+other (cytoreductives)" arm groups at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC at the time of registering into the study for a 5 year observation period.
OG001	Other (Cytoreductives)-Hydroxyurea	Participants who received other (Cytoreductives)-Hydroxyurea at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC, was observed for 5 years.

Secondary

Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy

Since the study is observational nature, interpreting the table is difficult due to inconsistencies in reporting the units of the dose.

Posted

Mean

Standard Deviation

milligram (mg)

Up to 5 years

ID	Title	Description
OG000	XAGRID Only	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC, was observed for 5 years.
OG001	Other (Cytoreductives)-Hydroxyurea	Participants who received other (Cytoreductives)-Hydroxyurea at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC, was observed for 5 years.
OG002	Other (Cytoreductives)-Interferon Alpha	Participants who received other (Cytoreductives)-Interferon Alpha at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC, was observed for 5 years.

Primary

Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events

SSAR: serious adverse event (SAE) that was considered related to cytoreductive therapy. SAE: any untoward medical occurrence that at any dose resulted in death, life-threatening (at the time of the event), in-patient hospitalization/prolongation of existing hospitalization (elective hospitalizations/procedures for pre-existing conditions that had not worsened were excluded), resulted in persistent or significant disability/incapacity or congenital abnormality/birth defect. Relatedness (suspected/not suspected) to XAGRID or other cytoreductive theraphy was determined by the investigator. As for SSARs, it was important to consider whether the events were related to XAGRID or other cytoreductive therapy. A participant was included in Xagrid or other treatment group based on treatment exposure, participants received Xagrid + Other was counted both in Xagrid and other treatment group.

Overall treatment safety population. All events/data were allocated to the treatment that a participant was receiving at the time of the event/assessment. Participants who had exposed to XAGRID (alone or in combination with other) was counted in Xagrid arm and those who had received other ET therapy in the "Other (Cytoreductives)".

Posted

Number

participants

Up to 5 years

ID	Title	Description
OG000	XAGRID	Participants who received XAGRID at a dose and mode of administration managed as per investigator's discretion and the relevant SmPC, was observed for 5 years.
OG001	Other (Cytoreductives)

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	XAGRID	Participants who received XAGRID from "Xagrid only" or "Xagrid+other (cytoreductives)" arm groups (for serious adverse events) at a dose and mode of administration managed as per investigator's discretion and the relevant Summary of Product Characteristics (SmPC) at the time of registering into the study or after switching from another treatment (other adverse events) any time during the 5 year observation period.			37	1,300	0	0
EG001	Other (Cytoreductives)	Participants who received other (cytoreductives) from " other (cytoreductives" or "Xagrid+other (cytoreductives)" arm groups (for serious adverse events) at a dose and mode of administration managed as per investigator's discretion and the relevant Summary of Product Characteristics (SmPC) at the time of registering into the study or after switching from another treatment (other adverse events) any time during the 5 year observation period. Other Cytoreductives included Hydroxyurea, Interferon- alpha, Pegylated interferon, Busulphan, Pipobroman, Sodium phosphate P32.			70	3,069	0	0

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0019 events9 affected3,069 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0012 events2 affected3,069 at risk
Splenic infarction	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0011 events1 affected3,069 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0012 events2 affected3,069 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0011 events1 affected3,069 at risk
Angina pectoris	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0006 events6 affected1,300 at risk EG0010 events0 affected3,069 at risk
Cardiac failure	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0002 events2 affected1,300 at risk EG0010 events0 affected3,069 at risk
Cardiac failure Congestive	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0003 events3 affected1,300 at risk EG0011 events1 affected3,069 at risk
Cardiomyopathy	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Left ventricular failure	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0002 events2 affected1,300 at risk EG0010 events0 affected3,069 at risk
Myocardial Infarction	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0002 events2 affected1,300 at risk EG0011 events1 affected3,069 at risk
Palpitations	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0003 events3 affected1,300 at risk EG0011 events1 affected3,069 at risk
Pericardial effusion	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Tachycardia	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0011 events1 affected3,069 at risk
Enteritis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0003 events3 affected1,300 at risk EG0012 events2 affected3,069 at risk
Haemorrhagic erosive gastritis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Melaena	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Asthenia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Pyrexia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Cellulitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Gastroenteritis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Klebsiella sepsis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Respiratory tract infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Skin injury	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Haemoglobin decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0016 events6 affected3,069 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0012 events2 affected3,069 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Metastases to adrenals	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0012 events2 affected3,069 at risk
Myelodysplastic syndrome transformation	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Myelofibrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Neoplasm skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Refractory anaemia with an excess of blasts	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0011 events1 affected3,069 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0012 events2 affected3,069 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0013 events3 affected3,069 at risk
Convulsion	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Headache	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0014 events4 affected3,069 at risk
Vasculitis cerebral	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Confusional state	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0011 events1 affected3,069 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0004 events3 affected1,300 at risk EG0010 events0 affected3,069 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0012 events2 affected3,069 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0003 events3 affected1,300 at risk EG0010 events0 affected3,069 at risk
Erythrosis	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0015 events5 affected3,069 at risk
Aneurysm ruptured	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0001 events1 affected1,300 at risk EG0010 events0 affected3,069 at risk
Venous thrombosis	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0000 events0 affected1,300 at risk EG0011 events1 affected3,069 at risk

Certain Agreements

ID	Term
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D013922	Thrombocytosis
D001791	Blood Platelet Disorders
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases
D006474	Hemorrhagic Disorders