Clinical Trial Results:
Aspirin for Optimising Pregnancy Outcome in Pregestational Diabetes: Pilot for The IRELAND Study (Investigating the Role of Early Low-dose Aspirin iN preexisting Diabetes)
Summary
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EudraCT number |
2014-001332-11 |
Trial protocol |
IE |
Global end of trial date |
06 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Apr 2020
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First version publication date |
04 Apr 2020
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Other versions |
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Summary report(s) |
EudraCT 2014-001332-11 Clinical Trial Report Summary |
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 |
IRELANDPILOTV1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Royal College of Surgeons Ireland
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Sponsor organisation address |
111 St Stephens Green, Dublin, Ireland, Dublin 2
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Public contact |
Mandy Jackson, Royal College of Surgeons, 00353 18093863, mandyjackson@rcsi.ie
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Scientific contact |
Mandy Jackson, Royal College of Surgeons, 00353 18093863, mandyjackson@rcsi.ie
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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 |
06 Dec 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Dec 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Dec 2016
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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 definitive IRELAND Study aims to investigate whether low-dose aspirin prescribed routinely to woman with pre-existing diabetes, initiated at 8+0 – 12 weeks’ gestation and continued until 36 weeks gestation may modify the risk of adverse perinatal outcomes related to placental dysfunction. The purpose of the pilot phase of this study is to determine rates of patient participation and compliance with aspirin therapy throughout pregnancy in this high-risk population.
Primary objectives:
1. Proportion of eligible women who agree to participate in the pilot study.
2. Compliance with the study protocol, as judged by platelet function monitoring
3. Proportion of study participants who complete the study, with complete ascertainment of laboratory markers of glycaemic control, renal function and platelet function at all scheduled timepoints
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Protection of trial subjects |
Not applicable
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Background therapy |
Not applicable | ||
Evidence for comparator |
The comparator group was a non treated (no aspirin) control group. The rationale for this control group is based on the lack of evidenced based recommendations (see NICE, RCOG, ACOG, HSE) for the use of aspirin in pregnant women with diabetes. | ||
Actual start date of recruitment |
26 May 2015
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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 |
Ireland: 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 |
24 subjects signed consent with one subject withdrawing consent prior to randomisation so 23 subjects were enrolled. Subjects were recruited from two maternity hospitals in Ireland. The first subject was recruited on 26-May-2015. | ||||||||||||
Pre-assignment
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Screening details |
40 subjects were screened. 16 of these patients screen failed due to reasons including; miscarriage before 12 weeks gestation, difficultly communicating in English, taking Aspirin in the first trimester before the recruitment phase, twin pregnancies, screening after 12 weeks gestation and diagnoses of diabetes < 6 months prior to recruitment. | ||||||||||||
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 | ||||||||||||
Blinding implementation details |
The trial was open label. No blinding of either the research participant or of the investigator occurred. Both the research participant and the investigator were aware of the investigational medicinal product that the research participant was allocated to receive.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Aspirin arm | ||||||||||||
Arm description |
Aspirin therapy 75mg daily commencing after a satisfactory 1st trimester assessment, to include sonographic confirmation of fetal cardiac activity followed by 4-weekly blood draws for platelet function (dynamic platelet assay), serum fructosamine and renal profile, with quantification of microalbuminuria in each trimester(aspirin arm). Prenatal care will be delivered through the Combined Obstetric Endocrine service. Aspirin was provided free of charge to the patient. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Aspirin (Acetylsalicylic acid) 75mg
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Investigational medicinal product code |
ATC code: B01A C06
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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 |
Arm 1: Aspirin Therapy: Aspirin 75mg daily commenced after satisfactory routine first trimester assessments, to include sonographic confirmation of foetal cardiac activity. Monthly blood was drawn during pregnancy up to week 36 for platelet function, serum fructosamine, and renal profile, with quantification of microalbuminuria in first and third trimester. Prenatal care was delivered as standard through the Combined Obstetric Endocrine service. Aspirin was provided free of charge to the participants through the local pharmacy in the hospital
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Arm title
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Control arm | ||||||||||||
Arm description |
Arm 2: Control Group: No aspirin therapy. Monthly blood was drawn during pregnancy up to week 36 for platelet function, serum fructosamine, and renal profile, with quantification of microalbuminuria in first and third trimester. Prenatal care was delivered as standard through the Combined Obstetric Endocrine service. | ||||||||||||
Arm type |
No intervention | ||||||||||||
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 |
Aspirin arm
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Reporting group description |
Aspirin therapy 75mg daily commencing after a satisfactory 1st trimester assessment, to include sonographic confirmation of fetal cardiac activity followed by 4-weekly blood draws for platelet function (dynamic platelet assay), serum fructosamine and renal profile, with quantification of microalbuminuria in each trimester(aspirin arm). Prenatal care will be delivered through the Combined Obstetric Endocrine service. Aspirin was provided free of charge to the patient. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control arm
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Reporting group description |
Arm 2: Control Group: No aspirin therapy. Monthly blood was drawn during pregnancy up to week 36 for platelet function, serum fructosamine, and renal profile, with quantification of microalbuminuria in first and third trimester. Prenatal care was delivered as standard through the Combined Obstetric Endocrine service. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Aspirin arm
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Reporting group description |
Aspirin therapy 75mg daily commencing after a satisfactory 1st trimester assessment, to include sonographic confirmation of fetal cardiac activity followed by 4-weekly blood draws for platelet function (dynamic platelet assay), serum fructosamine and renal profile, with quantification of microalbuminuria in each trimester(aspirin arm). Prenatal care will be delivered through the Combined Obstetric Endocrine service. Aspirin was provided free of charge to the patient. | ||
Reporting group title |
Control arm
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Reporting group description |
Arm 2: Control Group: No aspirin therapy. Monthly blood was drawn during pregnancy up to week 36 for platelet function, serum fructosamine, and renal profile, with quantification of microalbuminuria in first and third trimester. Prenatal care was delivered as standard through the Combined Obstetric Endocrine service. | ||
Subject analysis set title |
Overall
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Overall number of women who agreed to participate in the trial.
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End point title |
proportion of women who agree to participate in the study [1] | ||||||||||||
End point description |
This endpoint was assessed by counting the number of women who were approached to take part in the study, the number who agreed to take part and the number who dropped out or were subsequently included on an intention to treat basis only.
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End point type |
Primary
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End point timeframe |
4 month period
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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: This is a pilot study and so no statistical analysis (e.g. hypothesis tests) were performed. |
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Attachments |
Endpoint 1 supporting extract from final report |
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No statistical analyses for this end point |
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End point title |
compliance with study protocol [2] | ||||||
End point description |
Compliance with the study protocol – assessing the number of patients who
underwent all designated assessments as outlined within the designated time
period for set assessments as specified in the study protocol
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End point type |
Primary
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End point timeframe |
6-8 months
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Notes [2] - 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: This is a pilot study and so no statistical analysis (e.g. hypothesis tests) were performed. |
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Attachments |
Endpoint 2 supporting extract from final report |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All Adverse Events occurring during the study observed by the investigator or reported by the subject were captured from Visit 1 until the post delivery visit.
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Adverse event reporting additional description |
All Adverse Events occurring during the study observed by the investigator or reported by the subject, whether or not attributed to the study medication were recorded on the Case Report Form and all Serious Adverse Events were reported to the Sponsor within 24 hours of the site's knowledge of the event except for the non-reportable events
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Aspirin Group
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Reporting group description |
Subjects exposed to Aspirin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Non-aspirin group
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Reporting group description |
Control group who were not exposed to aspirin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: Non-serious adverse events were not reported by the investigator in the final study report. A summary of the Serious Adverse Events that occurred during the trial have been provided. |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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18 Jul 2016 |
The protocol Version 3, dated 29-Jan-2015 was substantially amended to Version 4, dated 18-Jul-2016 to include a list of non-reportable adverse events.
The protocol safety reporting section 12.1 was amended to list events anticipated in pregnancy as non-reportable events unless deemed by clinicians and/or investigators to occur to a disproportionate degree. These events are considered to be ‘normal and expected’ occurrences for the patient population and in particular were not influenced by the administration of aspirin. Treatment of these symptoms was as per clinical guidelines.
The following events were listed in the protocol as not requiring reporting: Nausea/ vomiting prior to 14 weeks’ gestational age Hospitalisation for labour and delivery Poor glycaemic control Hospitalisation for poor glycaemic control Pelvic girdle dysfunction Indigestion Fatigue Constipation Shortness of breath Urinary frequency/ nocturia
Migraine and tension headache Nosebleeds and bleeding gums Varicose veins Haemorrhoids Back pain Palpitations Carpal tunnel syndrome Fetal normal variants on ultrasound: Pyelectasis, choroid plexus cysts, echogenic intracardiac focus |
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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 |