Clinical Trial Results:
Does metformin improve pregnancy outcomes [ incidence of LGA (≥90% birth weight centile) babies onset of maternal Gestational Diabetes, hypertension, PET, shoulder dystocia, admission to SCBU) in obese non-diabetic women?
Summary
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EudraCT number |
2008-005892-83 |
Trial protocol |
GB |
Global end of trial date |
21 Aug 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Jun 2016
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First version publication date |
11 Jun 2016
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Other versions |
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 |
WCH/2008/001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01273584 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Epsom and St Helier University Hospitals NHS Trust
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Sponsor organisation address |
St Helier Hospital, Wrythe Lane, carshalton, Surrey, Carshalton, Surrey, United Kingdom, SM5 1AA
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Public contact |
Jyoti Balani, Epsom and St Helier University Hospitals NHS Trust, 44 0208296 2140, jyoti.balani@esth.nhs.uk
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Scientific contact |
Jyoti Balani, Epsom and St Helier University Hospitals NHS Trust, 44 0208296 2140, jyoti.balani@esth.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 |
20 Jul 2015
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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 |
21 Aug 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 |
There is substantial evidence that obesity in pregnancy contributes to increased morbidity and mortality for both mother and baby. The purpose of the study is whether management of obese non-diabetic pregnant women with standarised lifestyle intervention (diet and physical activity) and metformin will lead to improve maternal and peri-natal outcomes compared to lifestyle intervention alone. We aim to compare peri-natal outcomes in women randomised to the two home glucose monitoring protocols:
Group 1 - Standardised lifestyle intervention and placebo.
Group 2 - Standardised lifestyle intervnetion and metformin.
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Protection of trial subjects |
The dose of Metformin?placebo given was gradually increased by 1 tablet every week so that the gastric side effects were minimum.
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Background therapy |
Low glycaemic index carbohydrate diet and regular excercise was recommended to all patients | ||
Evidence for comparator |
It was a placebo controlled trial and placebo which matched Metformin were manufactured | ||
Actual start date of recruitment |
12 Oct 2010
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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: 450
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Worldwide total number of subjects |
450
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EEA total number of subjects |
450
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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) |
450
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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 |
October 2010 to June 2015 at 3 NHS Hospitals in the UK Epsom and St Helier Hospitals Kings College Hospital, Medway Maritime Hospital | |||||||||||||||
Pre-assignment
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Screening details |
1071 pregnant women with BMI>35 were screened. 227 women were excluded - 6 were < 18 years of age, 17 had fetus with fetal defect, 66 had history of previous GDM, 18 had medical problems, 6 had gastric bypass, 68 had hyperemesis, 25 were receiving metformin, 8 could not take metformin and 13 had miscarriage | |||||||||||||||
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 |
Investigator, Monitor, Data analyst, Subject | |||||||||||||||
Blinding implementation details |
Central randomisation was used and patients were given consecutive numbered boxes
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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 | |||||||||||||||
Arm description |
Metformin tablets | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Metformin
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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 |
Metfromin 500 mg started as 1 tablet twice a day and gradually increased by 1 tablet every week to acheive a maximum dose of 2 tablets 3 times a day
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Arm title
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Placebo arm | |||||||||||||||
Arm description |
Placebo tablets manufactured to look identical to the active comparator Metformin | |||||||||||||||
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 |
Same as Metformin
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Baseline characteristics reporting groups
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Reporting group title |
Metformin arm
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Reporting group description |
Metformin tablets | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo arm
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Reporting group description |
Placebo tablets manufactured to look identical to the active comparator Metformin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Metformin arm
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Reporting group description |
Metformin tablets | ||
Reporting group title |
Placebo arm
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Reporting group description |
Placebo tablets manufactured to look identical to the active comparator Metformin |
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End point title |
Median birth weight percentile | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
At the time of birth of the baby
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Statistical analysis title |
Intention to treat | |||||||||||||||
Comparison groups |
Metformin arm v Placebo arm
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Number of subjects included in analysis |
400
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.66 | |||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||
Confidence interval |
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End point title |
Median birth weight percentile | |||||||||||||||
End point description |
The birthweight dentile of the baby is calculated for all babies
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End point type |
Primary
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End point timeframe |
End of the trial
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Statistical analysis title |
Intention to treat principle | |||||||||||||||
Statistical analysis description |
Comparisons between groups were perfdormed with the use of Mann-Whitney U test
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Comparison groups |
Metformin arm v Placebo arm
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Number of subjects included in analysis |
400
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | |||||||||||||||
P-value |
= 0.66 [2] | |||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||
Parameter type |
Median difference (final values) | |||||||||||||||
Confidence interval |
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Notes [1] - Intention to treat analysis [2] - Not signifiant |
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Adverse events information
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Timeframe for reporting adverse events |
Throughout the Trial
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Adverse event reporting additional description |
Reporting of adverse events at each visit, reporting immediately in case of hospital admission
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Clinical terms | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
Nil
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Reporting groups
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Reporting group title |
Metformin arm
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Reporting group description |
Metformin tablets | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo arm
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Reporting group description |
Placebo tablets manufactured to look identical to the active comparator Metformin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 4.2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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05 Oct 2009 |
To make the trial a multicentre one
To include blood tests like Fasting Insulin |
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20 Nov 2009 |
Increase in Sample size |
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20 Nov 2009 |
Change in the composition of the placebo |
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15 Jun 2010 |
Addition of Clinical Trial infiormation card
Addition of medicine escalation sheet |
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25 Aug 2011 |
Sample size revised to 400 |
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10 May 2013 |
Change of Principal Investigator at 1 site |
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23 Sep 2013 |
Shipment of blood samples from one hospital site to another for storage |
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20 Oct 2014 |
Addition of 50 more patients- Total 450
Addition of Epworth sleepiness scale |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | ||||||||||
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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. | ||||||||||
Nil |