Clinical Trial Results:
Efficacy of Metformin in Pregnant Obese Women, a Randomised Controlled Trial.
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Summary
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EudraCT number |
2009-017134-47 |
Trial protocol |
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Global end of trial date |
30 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Jul 2020
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First version publication date |
04 Jul 2020
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Other versions |
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Summary report(s) |
SAP PUBLICATION |
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 |
EMPOWaR
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Additional study identifiers
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ISRCTN number |
ISRCTN51279843 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
CTA Number: 01384/0217/001-0001, UKCRN Ref: 8851, NIHR FUNDER REF: 8/246/09, Scotland A Research Ethics Committee: 10/MRE00/12 | ||
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Sponsors
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Sponsor organisation name |
University of Edinburgh
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Sponsor organisation address |
47 Little France Crescent, Edinburgh, United Kingdom, EH16 4TJ
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Public contact |
Marise Bucukoglu, University of Edinburgh, marise.bucukoglu@ed.ac.uk
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Scientific contact |
Marise Bucukoglu, University of Edinburgh, marise.bucukoglu@ed.ac.uk
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Sponsor organisation name |
NHS Lothian
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Sponsor organisation address |
47 Little France Crescent, Edinburgh, United Kingdom, EH16 4TJ
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Public contact |
Dougla Young, NHS Lothian, douglas.young@luht.scot.nhs.uk
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Scientific contact |
Dougla Young, NHS Lothian, douglas.young@luht.scot.nhs.uk
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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 |
30 Apr 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Apr 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Apr 2015
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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 |
The aim of this study is to determine if metformin, administered to obese women during pregnancy, reduces the future life risk of obesity and metabolic syndrome in their babies.
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Protection of trial subjects |
Participants who fulfilled all the potential eligibility criteria and who express an interest in the study had a blood test for renal and liver function and a formal glucose tolerance tests. These tests were performed after consent for the study is signed but before randomisation and women excluded where appropriate.
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Background therapy |
None | ||
Evidence for comparator |
An intervention with the drug metformin (an insulin sensitizing agent) using a comparator placebo to measure the outcome birthweight centile, a surrogate marker of future life risk of obesity and metabolic syndrome. Obesity causes adverse pregnancy outcomes, with a particular focus on insulin resistance (IR). Metformin reduces insulin resistance and is widely used to treat type II diabetes. Metformin has been shown to be safe during pregnancy and the National Institute for Health and Clinical Excellence (NICE) in the UK now recommends metformin as an alternative to insulin in women with established diabetes in pregnancy. Birthweight centile is an appropriate surrogate marker for the lifetime risk of obesity and metabolic syndrome. Increasing evidence suggests that adult obesity has its origins at or prior to birth, and that intrauterine events leading to high birthweight cause later life obesity. | ||
Actual start date of recruitment |
01 Feb 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 449
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Worldwide total number of subjects |
449
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EEA total number of subjects |
449
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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) |
449
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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 |
449 obese pregnant women in the UK were recruited between 01st Feb 2011 and 16th Jan 2014 | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants who fulfilled the intial eligibility criteria were sent an invitation letter and if women agreed they were consented to have a blood test. The results of which confirmed eligibiltiy prior to randomisation. Women were excluded, if they were identified with Gestational Diabetes, liver or Kidney disease. | |||||||||||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||||
Blinding implementation details |
Blinding was conducted externally by Merck Sante who supplied both the treatments. Unblinding envelopes (emergency or otherwise) were supplied to the local pharmacist. The pharmasist collected the name of the clinician requesting the unblinding, the reasons for it and sent notification of any unblinding to the sponsors.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Metformin | |||||||||||||||||||||||||||
Arm description |
Metformin (Glucophage) 500mg film-coated tablet (500- 2500mg) maximum tolerated dose. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
PL 03759/0012-0013
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Other name |
Glucophage
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Women prescribed metformin tablets up to 2500mg from 12-16 weeks gestation and will stop once they have delivered their baby.
Women will be asked to start with 500mg metformin (1 tablet, Once Daily) taken with food, increasing in week 2 by an increment of 500mg per day (in other words to 1 tablet, twice daily). Week 3: a further increment of 500mg per day (in other words to 1 tablet, three times daily). In the fourth week the women will increase the evening dose of metformin by a further 500mg and in the fifth week the morning dose will also be increased by a further 500mg.
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Matching Placebo | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
500mg up to 2500mg
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Metformin
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Reporting group description |
Metformin (Glucophage) 500mg film-coated tablet (500- 2500mg) maximum tolerated dose. | ||
Reporting group title |
Placebo
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Reporting group description |
Matching Placebo | ||
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End point title |
Z score of birthweight percentile | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Birth
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Statistical analysis title |
BirthWeight Centile | ||||||||||||
Comparison groups |
Metformin v Placebo
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Number of subjects included in analysis |
434
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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| Notes [1] - Intention to Treat |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All AEs and SAEs were recorded from the time a participant was randomised until after the last baby is born and discharged from hospital or the end of the postnatal period (28 days after the birth), which ever is sooner.
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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 |
0
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Not collected. AEs recorded in participant notes only. |
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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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04 Mar 2010 |
Additional information provided to the MHRA who considered this an amended request for CTA.
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20 Sep 2010 |
Protocol modified Version 2 Expanded details about the substudies PIL and consent forms amended |
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13 Apr 2011 |
Table of study assessments - errors corrected 1 hour GTT blood sample removed from visits Para 6.1 additional text added |
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30 Sep 2011 |
Change to reference range for entry liver function test clarification re exclusion criteria for GDM - in future
relate just to WHO and not SIGN guidelines |
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01 Sep 2012 |
Revision to the protocol for clarifications and addition of new sub study. |
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30 Sep 2013 |
Para 6.4 amendment and additional documents created for Qualitative interviews |
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10 Mar 2014 |
Para 6.4 and 9.11 updated to include payment for participants and inclusion of women as controls for a
vascular function, sub study. |
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24 Sep 2014 |
Updated protocol for clarification of outcomes to harmonise with statistical analysis plan Removal of sub-studies to which subjects were not recruited |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/26165398 http://www.ncbi.nlm.nih.gov/pubmed/27606384 http://www.ncbi.nlm.nih.gov/pubmed/25588785 |
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