Clinical Trial Results:
NIRTURE - A Randomised Trial of Early Insulin Therapy in Very Low Birth Weight Infants
Summary
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EudraCT number |
2004-002170-34 |
Trial protocol |
ES |
Global end of trial date |
15 Feb 2010
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jul 2016
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First version publication date |
31 Jul 2015
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Other versions |
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Summary report(s) |
SAE and AE Listing |
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 |
15/1/04
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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 |
Cambridge Univeristy Hospitals NHS foundation Trust
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Sponsor organisation address |
R&D office Box 146, Addenbrookes NHS Trust, Cambridge, United Kingdom, CB0 0QQ
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Public contact |
Diane Picton
, Cambridge University Hospitals NHS Foundation Trust
, 44 1223762944, dp223@medschl.cam.ac.uk
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Scientific contact |
Dr Kathy Bearsdall
, Cambridge University Hospitals NHS Foundation Trust
, 44 1223746791, kb274@medschl.cam.ac.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 2008
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Nov 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Feb 2010
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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 evaluate the effect of early fixed dose insulin on mortality in very low birth weight babies
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Protection of trial subjects |
Regular reporting of SAE’s and meetings held yearly
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Background therapy |
Insulin aspart with variable rate 20% dextrose support, Dose 0.05 units/kg/hour, Route of administration Continuous intravenous infusion in the first week of life | ||
Evidence for comparator |
Standard care | ||
Actual start date of recruitment |
04 Feb 2005
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
24 Months | ||
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 |
Spain: 25
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Country: Number of subjects enrolled |
United Kingdom: 108
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Country: Number of subjects enrolled |
Belgium: 211
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Country: Number of subjects enrolled |
Netherlands: 45
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Worldwide total number of subjects |
389
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EEA total number of subjects |
389
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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 |
389
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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) |
0
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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 |
Very low birth weight infants (<1500g) were recruited from neonatal intensive care units and randomised to receive either a continuous infusion of insulin (0.05 u/kg/hr) from within 24 hours of birth and for the first 7 days of life, or to act as controls and receive standard neonatal care. Recuitment opened in Feb 2005 & closed June/July 2007. | ||||||||||||||||||
Pre-assignment
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Screening details |
Screening for eligibility was performed in conjunction with the clinical team | ||||||||||||||||||
Period 1
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Period 1 title |
Start-end of study intervention (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention | ||||||||||||||||||
Arm description |
Early fixed dose insulin replacement | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Insulin Aspart
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Investigational medicinal product code |
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Other name |
Novorapid
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
0.05u/kg/hr
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Arm title
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Control | ||||||||||||||||||
Arm description |
Standard care | ||||||||||||||||||
Arm type |
Standard Care | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Intervention
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Reporting group description |
Early fixed dose insulin replacement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
Standard care | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention
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Reporting group description |
Early fixed dose insulin replacement | ||
Reporting group title |
Control
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Reporting group description |
Standard care |
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End point title |
Death on or before expected date of delivery (taken as date considered to be the most accurate estimate of delivery date). | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Death on or before expected date of delivery (taken as date considered to be the most accurate estimate of delivery date).
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Statistical analysis title |
Death before expected delivery date | ||||||||||||||||||
Statistical analysis description |
Fisher's exact test applied to the frequency table cross-classifying the binary endpoint (death before expected deliver date) against treatment arm
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Comparison groups |
Intervention v Control
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Number of subjects included in analysis |
389
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.2 | ||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||
Point estimate |
0.61
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
0.33 | ||||||||||||||||||
upper limit |
1.15 |
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Adverse events information [1]
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Timeframe for reporting adverse events |
24 hours
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Assessment type |
Non-systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
Protocol Based | ||
Dictionary version |
1
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Frequency threshold for reporting non-serious adverse events: 0% | |||
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: A listing of serious adverse events are given in an attachment |
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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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15 Oct 2004 |
Protocol changes post original submission
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25 Nov 2004 |
Change in Trial stastistician ,Secondary Endpoints and randomsiation procedure.
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17 Jun 2005 |
Change of Trial Statistician and DMC Statistician to ensure independence. Revised study documentation
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11 Jan 2006 |
Justification to allow recruitment to multiple trial
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19 Apr 2006 |
Follow up plans - Appendix 3 (follow-up protocol). Patient information sheets and consent forms V2 ( April 2006) |
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25 Jun 2006 |
Change of PI
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03 Apr 2007 |
Plans to follow-up participants through Office of National Stastistic (ONS)
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15 Aug 2007 |
Recruitment suspended
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13 Sep 2007 |
Recruitment stopped on ground of futility
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20 Jun 2008 |
Specifically requesting cause of death
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06 Sep 2009 |
Change of Sponsor. Sent in for notification only but reviewed formally by ethic committee |
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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/18971490 |