Thrombocythemia, Essential
Conditions
Brief summary
This is an observational safety study being conducted in Europe comparing patients taking Xagrid to patients taking other cytoreductive treatments. The plan is to enrol at least 750 subjects taking Xagrid with up to 3000 subjects taking other cytoreductive therapies. The study will collect follow up data for 5 years for each patient enrolled that will focus on collecting data related to pre-defined events (PDEs) and Suspected Serious Adverse Reactions (SSARs).
Interventions
None listed
Sponsors
Shire
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* High risk ET patients * Subjects who can give written informed consent. * Subjects taking cytoreductive therapy
Exclusion criteria
* Contraindications listed by the product being used. * Patient cannot be participating in another clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Up to 5 years | 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. |
| Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events | Up to 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate of Thrombohaemorrhagic Events | Up to 5 years | 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. |
| Platelet Count | Baseline, Month 6,12,18, 24, 30, 36, 42, 48, 54, 60 | — |
| Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | Up to 5 years | 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. |
| Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | Up to 5 years | Since the study is observational nature, interpreting the table is difficult due to inconsistencies in reporting the units of the dose. |
Countries
Cyprus, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Norway, Portugal, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
Participants who were newly diagnosed (received no treatment at the time of study registration) or previously diagnosed with essential thrombocythemia (ET), receiving or continuing previous cytoreductive therapy were recruited in the study
Pre-assignment details
Due to the non-interventional nature of the study, participants could be receiving XAGRID, XAGRID+Other (Cytoreductives), other (cytoreductives) and no essential thrombocythemia (ET) therapy. During the study participants could change the treatments.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 804 |
| 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. | 141 |
| 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. | 2,664 |
| 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. | 38 |
| Total | 3,647 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 65 | 16 | 360 | 5 |
| Overall Study | Lost to Follow-up | 91 | 14 | 351 | 2 |
| Overall Study | Never Initiated Treatment | 0 | 0 | 0 | 72 |
| Overall Study | Other | 64 | 2 | 134 | 6 |
| Overall Study | Participant request | 12 | 1 | 33 | 1 |
| Overall Study | Sponsor request | 9 | 0 | 30 | 1 |
Baseline characteristics
| Characteristic | XAGRID Only | XAGRID+Other (Cytoreductives) | Other (Cytoreductives) | No Essential Thrombocythemia (ET) Therapy | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 14.99 | 59.9 years STANDARD_DEVIATION 13.74 | 67.4 years STANDARD_DEVIATION 13.05 | 64.3 years STANDARD_DEVIATION 14.26 | 64.4 years STANDARD_DEVIATION 14.43 |
| Age, Customized 65-<75 years | 133 Participants | 30 Participants | 897 Participants | 13 Participants | 1073 Participants |
| Age, Customized Greater than equal to (>=)75 years | 96 Participants | 22 Participants | 854 Participants | 11 Participants | 983 Participants |
| Age, Customized Less than (<) 65 years | 575 Participants | 89 Participants | 913 Participants | 14 Participants | 1591 Participants |
| Sex: Female, Male Female | 501 Participants | 80 Participants | 1632 Participants | 25 Participants | 2238 Participants |
| Sex: Female, Male Male | 303 Participants | 61 Participants | 1032 Participants | 13 Participants | 1409 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 37 / 1,300 | 70 / 3,069 |
Outcome results
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.
Time frame: Up to 5 years
Population: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XAGRID Only | Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events | 37 participants |
| XAGRID+Other (Cytoreductives) | Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events | 70 participants |
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.
Time frame: Up to 5 years
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Non-haematological malignancy | 1.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myelodysplasia | 0.0 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Transient ischemic attack | 1.1 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Thrombohaemorrhagic events | 8.1 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Transformations | 4.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Severe Mucocutaneous Disorders | 0.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myelofibrosis | 3.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Intermittent Claudication/ digital ischaemia | 0.7 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pulmonary hypertension | 0.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pregnancy | 0.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pancreatitis | 0.0 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pulmonary fibrosis/ Interstitial pneumonia | 0.1 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other transformations | 0.1 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Venous thromboembolic events | 0.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Non-PDE death | 2.2 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myocardial infarction | 1.0 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Cardiomyopathy | 0.5 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Rhabdomyolysis/ myalgia | 0.2 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Angina | 0.7 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Major thrombotic events | 5.3 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Congestive heart failure | 1.2 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Major haemorrhagic events | 3.0 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other leukaemia | 0.6 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other cardiovascular symptoms | 5.8 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Arterial events | 4.9 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Acute leukaemia | 0.2 percentage of participants |
| XAGRID Only | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Stroke | 1.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Arterial events | 2.8 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other transformations | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Major haemorrhagic events | 0.7 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pregnancy | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Cardiomyopathy | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myocardial infarction | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Angina | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Congestive heart failure | 1.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other cardiovascular symptoms | 8.5 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Stroke | 1.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Transient ischemic attack | 0.7 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Severe Mucocutaneous Disorders | 1.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pulmonary hypertension | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pulmonary fibrosis/ Interstitial pneumonia | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Venous thromboembolic events | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pancreatitis | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Intermittent Claudication/ digital ischaemia | 0.7 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Transformations | 6.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myelofibrosis | 5.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myelodysplasia | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Acute leukaemia | 1.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other leukaemia | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Rhabdomyolysis/ myalgia | 0.0 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Non-haematological malignancy | 1.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Non-PDE death | 1.4 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Thrombohaemorrhagic events | 3.5 percentage of participants |
| XAGRID+Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Major thrombotic events | 2.8 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Stroke | 1.8 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Non-haematological malignancy | 4.6 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myelodysplasia | 0.5 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other cardiovascular symptoms | 3.2 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Transformations | 3.1 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Acute leukaemia | 1.0 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Congestive heart failure | 1.2 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Thrombohaemorrhagic events | 8.5 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other leukaemia | 0.5 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Major haemorrhagic events | 1.6 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myocardial infarction | 1.5 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Other transformations | 0.1 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Rhabdomyolysis/ myalgia | 0.1 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Angina | 0.7 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pulmonary fibrosis/ Interstitial pneumonia | 0.3 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Cardiomyopathy | 0.3 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Venous thromboembolic events | 1.9 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pulmonary hypertension | 0.2 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Major thrombotic events | 7.3 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pancreatitis | 0.1 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Severe Mucocutaneous Disorders | 2.4 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Non-PDE death | 3.9 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Intermittent Claudication/ digital ischaemia | 0.6 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Transient ischemic attack | 1.3 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Arterial events | 5.5 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pregnancy | 0.5 percentage of participants |
| Other (Cytoreductives) | Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Myelofibrosis | 1.1 percentage of participants |
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.
Time frame: Up to 5 years
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XAGRID Only | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 29096.2 milligram (mg) | Standard Deviation 291472.25 |
| XAGRID+Other (Cytoreductives) | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 957751.4 milligram (mg) | Standard Deviation 883174.77 |
| Other (Cytoreductives) | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 3592.2 milligram (mg) | Standard Deviation 5076.77 |
| No Essential Thrombocythemia (ET) Therapy | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 5103.1 milligram (mg) | Standard Deviation 10730.47 |
| Other (Cytoreductives)-Busulphan | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 7749.6 milligram (mg) | Standard Deviation 56031.79 |
| Other (Cytoreductives)-Pipobroman | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 28612.7 milligram (mg) | Standard Deviation 67374.96 |
| Other (Cytoreductives)-Sodium Phosphate P32 | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 2745.0 milligram (mg) | — |
| Other (Cytoreductives)-Thromboreductin | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 2140.0 milligram (mg) | Standard Deviation 835.26 |
| Other | Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | 111639.7 milligram (mg) | Standard Deviation 190370.57 |
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.
Time frame: Up to 5 years
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XAGRID Only | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 1213.7 days | Standard Deviation 687.83 |
| XAGRID+Other (Cytoreductives) | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 1382.3 days | Standard Deviation 609.33 |
| Other (Cytoreductives) | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 933.3 days | Standard Deviation 748.09 |
| No Essential Thrombocythemia (ET) Therapy | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 744.0 days | Standard Deviation 660.93 |
| Other (Cytoreductives)-Busulphan | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 510.2 days | Standard Deviation 560.28 |
| Other (Cytoreductives)-Pipobroman | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 992.8 days | Standard Deviation 690.8 |
| Other (Cytoreductives)-Sodium Phosphate P32 | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 39.7 days | Standard Deviation 96.73 |
| Other (Cytoreductives)-Thromboreductin | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 979.0 days | Standard Deviation 859.27 |
| Other | Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | 446.3 days | Standard Deviation 561.46 |
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.
Time frame: Up to 5 years
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XAGRID Only | Event Rate of Thrombohaemorrhagic Events | 2.75 participants/100 participant-years |
| XAGRID+Other (Cytoreductives) | Event Rate of Thrombohaemorrhagic Events | 2.86 participants/100 participant-years |
| Other (Cytoreductives) | Event Rate of Thrombohaemorrhagic Events | 2.60 participants/100 participant-years |
| No Essential Thrombocythemia (ET) Therapy | Event Rate of Thrombohaemorrhagic Events | 4.91 participants/100 participant-years |
Secondary
Platelet Count
Time frame: Baseline, Month 6,12,18, 24, 30, 36, 42, 48, 54, 60
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| XAGRID Only | Platelet Count | Month 60 (n = 523, 167, 1586, 144) | 1174.87 10^9 per Liter (10^9/L) | Standard Deviation 17473.437 |
| XAGRID Only | Platelet Count | Month 24 (n= 673, 181, 2106, 119) | 865.09 10^9 per Liter (10^9/L) | Standard Deviation 11047.483 |
| XAGRID Only | Platelet Count | Month 36 (n= 628, 167, 1917, 124) | 423.10 10^9 per Liter (10^9/L) | Standard Deviation 153.278 |
| XAGRID Only | Platelet Count | Month 30 (n= 642, 183, 2001, 116) | 418.97 10^9 per Liter (10^9/L) | Standard Deviation 159.129 |
| XAGRID Only | Platelet Count | Month 48 (n= 581, 167, 1735, 131) | 2461.07 10^9 per Liter (10^9/L) | Standard Deviation 28879.771 |
| XAGRID Only | Platelet Count | Month 54 (n= 557, 164, 1644, 132) | 413.93 10^9 per Liter (10^9/L) | Standard Deviation 145.601 |
| XAGRID Only | Platelet Count | Month 6 (n = 777, 145, 2469, 60) | 1093.73 10^9 per Liter (10^9/L) | Standard Deviation 17634.779 |
| XAGRID Only | Platelet Count | Month 12 (n= 739, 158, 2400, 81) | 969.61 10^9 per Liter (10^9/L) | Standard Deviation 14404.677 |
| XAGRID Only | Platelet Count | Baseline (n = 671, 120, 2279,136) | 486.90 10^9 per Liter (10^9/L) | Standard Deviation 210.106 |
| XAGRID Only | Platelet Count | Month 42 (n= 597, 161, 1799, 138) | 831.62 10^9 per Liter (10^9/L) | Standard Deviation 10257.081 |
| XAGRID Only | Platelet Count | Month 18 (n= 706, 170, 2231, 86) | 1612.14 10^9 per Liter (10^9/L) | Standard Deviation 22193.573 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 36 (n= 628, 167, 1917, 124) | 1138.81 10^9 per Liter (10^9/L) | Standard Deviation 8787.658 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 6 (n = 777, 145, 2469, 60) | 521.44 10^9 per Liter (10^9/L) | Standard Deviation 266.512 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 24 (n= 673, 181, 2106, 119) | 492.67 10^9 per Liter (10^9/L) | Standard Deviation 194.534 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 60 (n = 523, 167, 1586, 144) | 466.31 10^9 per Liter (10^9/L) | Standard Deviation 193.689 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 54 (n= 557, 164, 1644, 132) | 447.17 10^9 per Liter (10^9/L) | Standard Deviation 171.608 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 42 (n= 597, 161, 1799, 138) | 466.83 10^9 per Liter (10^9/L) | Standard Deviation 205.575 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 30 (n= 642, 183, 2001, 116) | 467.37 10^9 per Liter (10^9/L) | Standard Deviation 170.733 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 48 (n= 581, 167, 1735, 131) | 443.91 10^9 per Liter (10^9/L) | Standard Deviation 173.453 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Baseline (n = 671, 120, 2279,136) | 542.77 10^9 per Liter (10^9/L) | Standard Deviation 250.44 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 18 (n= 706, 170, 2231, 86) | 541.78 10^9 per Liter (10^9/L) | Standard Deviation 706.564 |
| XAGRID+Other (Cytoreductives) | Platelet Count | Month 12 (n= 739, 158, 2400, 81) | 516.66 10^9 per Liter (10^9/L) | Standard Deviation 245.789 |
| Other (Cytoreductives) | Platelet Count | Month 12 (n= 739, 158, 2400, 81) | 436.64 10^9 per Liter (10^9/L) | Standard Deviation 154.958 |
| Other (Cytoreductives) | Platelet Count | Month 48 (n= 581, 167, 1735, 131) | 1360.17 10^9 per Liter (10^9/L) | Standard Deviation 20669.182 |
| Other (Cytoreductives) | Platelet Count | Month 60 (n = 523, 167, 1586, 144) | 1362.94 10^9 per Liter (10^9/L) | Standard Deviation 19098.693 |
| Other (Cytoreductives) | Platelet Count | Baseline (n = 671, 120, 2279,136) | 471.29 10^9 per Liter (10^9/L) | Standard Deviation 201.62 |
| Other (Cytoreductives) | Platelet Count | Month 6 (n = 777, 145, 2469, 60) | 439.44 10^9 per Liter (10^9/L) | Standard Deviation 153.766 |
| Other (Cytoreductives) | Platelet Count | Month 18 (n= 706, 170, 2231, 86) | 432.99 10^9 per Liter (10^9/L) | Standard Deviation 145.694 |
| Other (Cytoreductives) | Platelet Count | Month 24 (n= 673, 181, 2106, 119) | 1025.11 10^9 per Liter (10^9/L) | Standard Deviation 15888.471 |
| Other (Cytoreductives) | Platelet Count | Month 30 (n= 642, 183, 2001, 116) | 693.30 10^9 per Liter (10^9/L) | Standard Deviation 8293.353 |
| Other (Cytoreductives) | Platelet Count | Month 36 (n= 628, 167, 1917, 124) | 1221.09 10^9 per Liter (10^9/L) | Standard Deviation 20612.96 |
| Other (Cytoreductives) | Platelet Count | Month 42 (n= 597, 161, 1799, 138) | 1898.48 10^9 per Liter (10^9/L) | Standard Deviation 26724.419 |
| Other (Cytoreductives) | Platelet Count | Month 54 (n= 557, 164, 1644, 132) | 1771.77 10^9 per Liter (10^9/L) | Standard Deviation 25187.992 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 60 (n = 523, 167, 1586, 144) | 425.22 10^9 per Liter (10^9/L) | Standard Deviation 268.377 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 36 (n= 628, 167, 1917, 124) | 462.06 10^9 per Liter (10^9/L) | Standard Deviation 256.357 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 12 (n= 739, 158, 2400, 81) | 501.46 10^9 per Liter (10^9/L) | Standard Deviation 275.88 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 6 (n = 777, 145, 2469, 60) | 545.30 10^9 per Liter (10^9/L) | Standard Deviation 202.936 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 54 (n= 557, 164, 1644, 132) | 408.41 10^9 per Liter (10^9/L) | Standard Deviation 254.971 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 42 (n= 597, 161, 1799, 138) | 463.52 10^9 per Liter (10^9/L) | Standard Deviation 271.69 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Baseline (n = 671, 120, 2279,136) | 837.23 10^9 per Liter (10^9/L) | Standard Deviation 377.104 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 48 (n= 581, 167, 1735, 131) | 457.44 10^9 per Liter (10^9/L) | Standard Deviation 250.165 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 30 (n= 642, 183, 2001, 116) | 467.54 10^9 per Liter (10^9/L) | Standard Deviation 255.641 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 24 (n= 673, 181, 2106, 119) | 499.29 10^9 per Liter (10^9/L) | Standard Deviation 249.164 |
| No Essential Thrombocythemia (ET) Therapy | Platelet Count | Month 18 (n= 706, 170, 2231, 86) | 476.72 10^9 per Liter (10^9/L) | Standard Deviation 245.45 |