Clinical Trial Results:
An Open Label, Non-Randomised, Phase IV Clinical Trial to Determine the Transfer of Apixaban and Rivaroxaban in Breast Milk Following Oral Administration
Summary
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EudraCT number |
2018-003852-19 |
Trial protocol |
GB |
Global end of trial date |
07 Mar 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Mar 2021
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First version publication date |
28 Mar 2021
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Other versions |
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Summary report(s) |
Clinical Study report |
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 |
DOAC
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Roopen Arya, King's College London, +44 02032993570, roopen.arya@nhs.net
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Scientific contact |
Roopen Arya, King's College London, +44 02032993570, roopen.arya@nhs.net
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Sponsor organisation name |
King's College Hospital NHS Foundation Trust
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Sponsor organisation address |
Denmark Hill, London, United Kingdom, SE5 9RS
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Public contact |
Roopen Arya, King's college Hospital NHS Foundation Trust, +44 02032993570, roopen.arya@nhs.net
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Scientific contact |
Roopen Arya, King's college Hospital NHS Foundation Trust, +44 02032993570, roopen.arya@nhs.net
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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 |
15 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Mar 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Mar 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine if apixaban and rivaroxaban are excreted in breastmilk following single dose oral administration to breastfeeding mothers.
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Protection of trial subjects |
Subjects had the right to withdraw from the study at any time for any reason.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jan 2020
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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 |
United Kingdom: 3
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Worldwide total number of subjects |
3
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EEA total number of subjects |
3
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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) |
3
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Potential study subjects were invited to participate in this trial via multiple routes, such as advertisements post on websites, and invitation letters enclosed with PIS sent to those women who had delivered their babies at King’s College Hospital NHS Foundation Trust in the preceding year, and had been administrated LMWH during pregnancy. | |||||||||
Pre-assignment
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Screening details |
The assessment included participant’s age, duration of gestation, date of delivery, feeding regimen (exclusive breastfeeding or mixed feeding), smoking history, alcohol history, medical history, ongoing medication, blood pressure, and pulse. Laboratory tests were performed,including haematology tests,biochemistry tests,pregnancy test, and serology. | |||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
Open label
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Apixaban | |||||||||
Arm description |
5 mg of Apixaban (Eliquis®)(twice daily) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Apixaban
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Investigational medicinal product code |
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Other name |
Eliquis
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Single dose of 5 mg (twice daily).
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Arm title
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Rivaroxaban | |||||||||
Arm description |
Rivaroxaban 20mg (once daily) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Rivaroxaban
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Investigational medicinal product code |
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Other name |
Xarelto
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Single dose of 20mg (once daily)
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Baseline characteristics reporting groups
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Reporting group title |
Apixaban
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Reporting group description |
5 mg of Apixaban (Eliquis®)(twice daily) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rivaroxaban
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Reporting group description |
Rivaroxaban 20mg (once daily) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Apixaban
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Reporting group description |
5 mg of Apixaban (Eliquis®)(twice daily) | ||
Reporting group title |
Rivaroxaban
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Reporting group description |
Rivaroxaban 20mg (once daily) |
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End point title |
Concentration in milk [1] [2] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0 to 24 hours
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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: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. |
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No statistical analyses for this end point |
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End point title |
Concentration in milk [3] [4] | ||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0 to 24 hours
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Notes [3] - 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: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. |
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No statistical analyses for this end point |
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End point title |
Concentration in plasma [5] [6] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0 to 24 hours
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Notes [5] - 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: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. |
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No statistical analyses for this end point |
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End point title |
Concentration in plasma [7] [8] | ||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0 to 24 hours
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Notes [7] - 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: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Due to the nature of the study, descriptive statistics will be used to analyse the data and describe the study population. |
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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 |
AEs and SAEs will be reported from first dose until 24 hours following first dose.
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Adverse event reporting additional description |
AEs listed in the SmPC do not need to be reported.
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Assessment type |
Non-systematic | |||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
Apixaban
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Reporting group description |
5 mg of Apixaban (Eliquis®)(twice daily) | |||||||||||||||||||||
Reporting group title |
Rivaroxaban
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Reporting group description |
Rivaroxaban 20mg (once daily) | |||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||
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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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12 Jun 2019 |
IMP change: Dabigatran changed to Apixaban.
Change occurred prior to recruitment start. |
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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. | |||
The final subject was unable to be recruited due to the COVID-19 pandemic. |