Clinical Trial Results:
The ELTION study – A multicenter open-label interventional study of Eltrombopag in patients with poor graft function after allogeneic hematopoietic stem cell transplantation
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Summary
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EudraCT number |
2018-001129-15 |
Trial protocol |
ES |
Global end of trial date |
03 Nov 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Nov 2021
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First version publication date |
19 Nov 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CETB115EES03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03718533 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Nov 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Nov 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of eltrombopag for poor graft function on overall hematologic response (partial and complete) as determined by platelets, hemoglobin and neutrophil counts, by 16 weeks after the initiation of eltrombopag.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
9
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted across 7 centers in 1 country (Spain). | ||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 25 participants were screened in this study of which 15 failed screening and 10 participants were enrolled in the study. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Eltrombopag | ||||||||||||||||||||
Arm description |
Patients received eltrombopag orally once daily up to 36 weeks. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Eltrombopag
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Investigational medicinal product code |
ETB115
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Eltrombopag was provided as 50 mg or 25 mg film-coated tablets for oral use administration
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Baseline characteristics reporting groups
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Reporting group title |
Eltrombopag
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Reporting group description |
Patients received eltrombopag orally once daily up to 36 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Eltrombopag
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Reporting group description |
Patients received eltrombopag orally once daily up to 36 weeks. | ||
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End point title |
Hematologic response rate by 16 weeks after the initiation of eltrombopag [1] | ||||||||
End point description |
Hematologic response rate was defined as the percentage of participants who met the criteria of either complete response (CR) or partial response (PR) by Week 16. PR was defined when any of the following: Platelet count ≥ 20000/microliter(μL) (with platelet transfusion independence), absolute neutrophil count (ANC) ≥1000/μL (when pretreatment ANC was <1000/μL) and/or hemoglobin (Hb) ≥100 gram(g)/ liter(L) (when pretreatment Hb was <100g/L) (with red blood cells transfusion independence), confirmed in two blood tests separated a minimum of 7 days. CR was defined when all of the following: platelet count ≥100000/μL, ANC ≥1500/μL (when pretreatment ANC was <1000/μL) and Hb ≥110 g/L (when pretreatment Hb was <100g/L), confirmed in two blood tests separated a minimum of 7 days. Participants who discontinued before Week 16 were considered as responders if, in the last evaluation, they had PR or CR. The 95% Confidence Interval (CI) was the binomial exact CI based on Clopper-Pearson method.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 16
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this outcome measure |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants who had a response in the neutrophil lineage | ||||||||||||||||||
End point description |
Percentage of participants who had a response (partial or complete) in the neutrophil lineage. A partial response in the neutrophil lineage was defined as absolute neutrophil count (ANC) ≥1000/ µL (when pretreatment ANC was <1000/μL) confirmed in two consecutive blood tests separated a minimum of 7 days. A complete response in the neutrophil lineage was defined as ANC ≥ 1500/ µL (when pretreatment ANC was <1000/μL) confirmed in two consecutive blood tests separated a minimum of 7 days.
Analysis population: All participants to whom study treatment was assigned and pretreatment ANC was <1000 µL. Only those participants who reached the study week were analyzed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Week 16, 20, 24, 30 and 36
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of participants who had a response in the platelet lineage | ||||||||||||||||||
End point description |
Percentage of participants who had a response (partial or complete) in the platelet lineage. A partial response in the platelet lineage was defined as platelet count ≥20000/µL (with platelet transfusion independence) confirmed in two consecutive blood tests separated a minimum of 7 days. A complete response in the platelet lineage was defined as platelet count ≥ 100000/µL confirmed in two consecutive blood tests separated a minimum of 7 days.
Analysis population: All participants to whom study treatment was assigned. Only those participants who reached the study week were analyzed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Week 16, 20, 24, 30 and 36
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of participants who had a response in the hemoglobin lineage | ||||||||||||||||||
End point description |
Percentage of participants who had a response (partial or complete) in the hemoglobin (Hb) lineage. A partial response in the Hb lineage was defined as Hb ≥100 g/L (when pretreatment Hb was <100g/L) (with red blood cells transfusion independence), confirmed in two consecutive blood tests separated a minimum of 7 days. A complete response in the Hb lineage was defined as Hb≥ 110 g/L (when pretreatment Hb was <100g/L) confirmed in two consecutive blood tests separated a minimum of 7 days.
Analysis population: All participants to whom study treatment was assigned and pretreatment Hb <100g/L. Only those participants who reached the study week were analyzed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Week 16, 20, 24, 30 and 36
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of participants with hematologic response (partial and complete) at Week 24 and 36 | ||||||||||||
End point description |
Percentage of participants who met the criteria of either CR or PR at 24 weeks and 36 weeks after the initiation of eltrombopag. PR was defined when any of the following: Platelet count ≥20000/microliter (μL) (with platelet transfusion independence), absolute neutrophil count (ANC) ≥1000/μL (when pretreatment ANC was <1000/μL) and/or hemoglobin (Hb) ≥100 gram (g)/ liter (L) (when pretreatment Hb was <100g/L) (with RBC transfusion independence), confirmed in two blood tests separated a minimum of 7 days. CR was defined when all three of the following: platelet count ≥100000/μL, ANC ≥1500/μL (when pretreatment ANC was <1000/μL) and Hb ≥110 g/L (when pretreatment Hb was <100g/L), confirmed in two blood tests separated a minimum of 7 days.
Analysis population: All participants to whom study treatment was assigned. Only those participants who reached the study week were analyzed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Week 24 and 36
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants who were previously platelet transfusion-dependent and did no longer require platelet transfusions after the initiation of eltrombopag | ||||||||||||
End point description |
Percentage of participants who received at least one platelet transfusion before starting treatment and who did no longer require platelet transfusion before and after the first 16 weeks of treatment.
Analysis population: All participants to whom study treatment was assigned and who received at least one platelet transfusion before starting treatment. Only those participants with evaluable data at the specified time points for this outcome measure were analyzed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
From start of treatment to end of treatment, assessed up to 36 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants who were previously red blood cells transfusion-dependent and did no longer require red blood cells transfusions | ||||||||||||
End point description |
Percentage of participants who received at least one red blood cells transfusion before starting treatment and who did no longer require red blood cells transfusion before and after the first 16 weeks of treatment.
Analysis population: All participants to whom study treatment was assigned and who received at least one red blood cells transfusion before starting treatment. Only those participants with evaluable data at the specified time points for this outcome measure were analyzed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
From start of treatment to end of treatment, assessed up to 36 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Duration of transfusion independence | ||||||||
End point description |
Duration of transfusion independence defined as the period of time where participants did not receive any platelet or red blood cells transfusions during the treatment period
Analysis population: All participants to whom study treatment was assigned.
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End point type |
Secondary
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End point timeframe |
From start of treatment to end of treatment, assessed up to 36 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants who discontinued or reduced the use of concomitant erythropoietin (EPO) therapy | ||||||||||||
End point description |
Percentage of participants who discontinued or reduced by ≥50% from baseline the use of concomitant EPO therapy while receiving eltrombopag.
Analysis population: All participants to whom study treatment was assigned with evaluable data for this outcome measure
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End point type |
Secondary
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End point timeframe |
From start of treatment to end of treatment, assessed up to Week 36
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants who discontinued or reduced the use of concomitant granulocyte colony-stimulating factor (G-CSF) therapy | ||||||||||||
End point description |
Percentage of participants who discontinued or reduced by ≥50% from baseline the use of concomitant G-CSF therapy while receiving eltrombopag.
Analysis population: All participants to whom study treatment was assigned with evaluable data for this outcome measure
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End point type |
Secondary
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End point timeframe |
From start of treatment to end of treatment, assessed up to Week 36
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall survival (OS) | ||||||||
End point description |
OS defined as the time from the date of inclusion until the date of death due to any cause was calculated using Kaplan-Meier estimated. All patients who discontinued from the study, regardless the reason of discontinuation, were followed for survival, unless they withdrew their consent, died or were lost-to follow-up, in which case were censored at the last contact.
Note: 9999 indicates that median OS was not reached
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End point type |
Secondary
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End point timeframe |
From start of treatment until the date of death, assessed up to 40 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall survival rate at 24 and 36 weeks | ||||||||||||
End point description |
Overall survival rate defined as the rate estimate of the percentage of participants who were alive at 24 and 36 weeks. All patients who discontinued from the study, regardless the reason of discontinuation, were followed for survival at Week 24 and 36, unless they withdrew their consent, died or were lost-to follow-up, in which case were censored at the last contact.
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End point type |
Secondary
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End point timeframe |
Week 24 and 36
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From day of first dose of study medication to the last dose of study medication plus 30 days, up to 40 weeks
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Adverse event reporting additional description |
Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Eltrombopag
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Reporting group description |
Patients received eltrombopag orally once daily up to 36 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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10 Jul 2019 |
The purpose of this protocol amendment was to update the eligibility criteria for better clarifying the profile of patients to be included, and align with the current eltrombopag program risk language. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
