Clinical Trial Results:
A Feasibility study looking at the use of Glibenclamide and metfoRmin versus stAndard Care in gEstational diabeteS
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Summary
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EudraCT number |
2013-004706-25 |
Trial protocol |
GB |
Global end of trial date |
01 Nov 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) |
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 |
V1290413
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02080377 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
ETHICS: 13/SS/0223 , CSO Funder: CZH/4/10 | ||
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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
Head of Research Governance, University of Edinburgh, +44 131 242 6623, marise.bucukoglu@ed.ac.uk
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Scientific contact |
Marise Bucukoglu
Head of Research Governance, University of Edinburgh, +44 131 242 6623, 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 |
Dr. Heather Charles
Head of Research Governance, Professor Jane Norman
University of Edinburgh, +44 1312423325, ACCORD@nhslothian.scot.nhs.uk
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Scientific contact |
Dr. Heather Charles
Head of Research Governance, Professor Jane Norman
University of Edinburgh, +44 1312423325, ACCORD@nhslothian.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 Oct 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Oct 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Nov 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 feasibility study is to determine recruitment rates to a randomised trial of glibenclamide compared with insulin (both in addition to maximum tolerated metformin) for the treatment of gestational diabetes. Additionally, we will compare glycaemic control in the two groups, and evaluate acceptability. Finally, we will collect information on a range of clinical and biochemical outcomes to inform the design of a large definitive randomised trial.
Primary outcome: The number of women who agree to be randomised.
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Protection of trial subjects |
The trial steering committee will monitor participants’ glucose readings, paying particular attention to number and frequency of episodes of hypoglycaemia. If it is deemed that there are too many incidences of hypoglycaemia in the intervention arm then the intervention could be withdrawn and the trial stopped prematurely.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2014
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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: 23
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Worldwide total number of subjects |
23
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EEA total number of subjects |
23
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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) |
23
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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 |
Participants were given verbal and written information about the study at the time of diagnosis of GDM. Prior to recruitment, treatment with metformin was commenced if women were failing to achieve adequate glycaemic control with lifestyle measures alone, according to standard practice. | |||||||||
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Pre-assignment
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Screening details |
All women with GDM attending the selected sites who fail monotherapy and do not meet any of the exclusion criteria will be considered to be eligible | |||||||||
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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 |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Glibenclamide | |||||||||
Arm description |
The primary aim of this feasibility study is to determine recruitment rates to a randomised trial of glibenclamide compared with insulin (both in addition to maximum tolerated metformin) for the treatment of gestational diabetes mellitus. Secondary aims will be to compare glycaemic control in the two groups, evaluate acceptability and to collect information on a range of clinical outcomes to inform the design of a large definitive randomised trial. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Glibenclamide
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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 |
glibenclamide in either a 2.5 mg or 5 mg tablet. The usual dosage of glyburide is 2.5–20 mg daily in divided doses, although pharmacokinetic studies during pregnancy indicate daily doses up to 30 mg may be necessary to achieve adequate control” [15,16]. Of note, none of the six referees of the grant application related to this protocol have commented adversely on the dose of glibenclamide (reports available on request).
The dose will alter according to the clinician’s recommendations, following a strict dosing algorithm drawn up prior to the study commencing
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Arm title
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Insulin | |||||||||
Arm description |
- | |||||||||
Arm type |
Standard Care | |||||||||
Investigational medicinal product name |
Insulin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
AS required
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Baseline characteristics reporting groups
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Reporting group title |
Glibenclamide
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Reporting group description |
The primary aim of this feasibility study is to determine recruitment rates to a randomised trial of glibenclamide compared with insulin (both in addition to maximum tolerated metformin) for the treatment of gestational diabetes mellitus. Secondary aims will be to compare glycaemic control in the two groups, evaluate acceptability and to collect information on a range of clinical outcomes to inform the design of a large definitive randomised trial. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Insulin
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Reporting group description |
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End points reporting groups
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Reporting group title |
Glibenclamide
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Reporting group description |
The primary aim of this feasibility study is to determine recruitment rates to a randomised trial of glibenclamide compared with insulin (both in addition to maximum tolerated metformin) for the treatment of gestational diabetes mellitus. Secondary aims will be to compare glycaemic control in the two groups, evaluate acceptability and to collect information on a range of clinical outcomes to inform the design of a large definitive randomised trial. | ||
Reporting group title |
Insulin
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Reporting group description |
- | ||
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End point title |
Number of women Randomised | |||||||||
End point description |
The primary endpoint is the number (and corresponding throughput) of women who agree to be randomised
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End point type |
Primary
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End point timeframe |
Randomisation
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Statistical analysis title |
Number of women agreed to randomisation | |||||||||
Comparison groups |
Glibenclamide v Insulin
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Number of subjects included in analysis |
23
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
< 0.05 [2] | |||||||||
Method |
Poisson distribution | |||||||||
Confidence interval |
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| Notes [1] - Feasability [2] - As this was a feasibility study a formal power calculation was not considered appropriate |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All AEs and SAEs will be recorded from the time a participant signs the consent form to take part in the study until stopping the IMP or discharge following delivery of the baby, whichever is later
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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: All adverse medical events reported by the participant were noted in the participant’s hospital notes, together with a note of the date of starting, the duration, and any medical treatment received. The clinician will assess ALL reported AEs. |
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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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24 Apr 2014 |
Increased detail, changes to flow chart, change in secondary outcomes, NIMP and Imp supply, clarification on rand process, stats analysis and TSC/DMC details |
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17 Dec 2014 |
Lower limit of gestation (weeks) from 20+0 weeks gestation to 16+0 weeks gestation. It also includes some minor clarifications in the protocol, consent form and PIL, as well as the opening of recruitment in another hospital |
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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 limitations of the study include the small sample size, which could have contributed to a chance imbalance on prognostic factors including weight and time of diagnosis. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28938877 |
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