E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pregestational diabetes represents a high-risk for evolution of preeclampsia (PET), with rates of PET within this group at approximately 20%. The combination of diabetes and preeclampsia places the pregnancy at heightened risk for hypoxia and stillbirth. Placental dysfunction, due to disordered early placental development, is central to the disease process. |
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E.1.1.1 | Medical condition in easily understood language |
Pre-eclampsia can lead to serious complications for mother and baby and patients with pre-exisiting diabetes are at a higher risk of developing PET. Aspirin treatment can help reduce this risk. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | 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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E.2.2 | Secondary objectives of the trial |
Examination, through dynamic platelet function assay, of antiplatelet effect among women with pregestational diabetes when compared with platelet function in diabetic women not taking antiplatelet therapy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria People who satisfy all of the following may be included in the study: 1. All women with type I or type II diabetes of at least 6 months duration prior to conception. 2. Ability to speak and read English 3. Singleton pregnancy at <12 weeks’ gestational age with documented fetal cardiac activity 4. Those willing to sign voluntarily a statement of informed consent to participate in the study. |
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E.4 | Principal exclusion criteria |
Exclusion criteria The following patients will be excluded from participation in the study: 1. Aspirin hypersensitivity (prior bronchospasm/ urticarial/ angioedema with aspirin), 2. Peptic ulcer disease 3. Known bleeding diathesis 4. Multifetal gestation 5. Severe early-onset preeclampsia in a previous pregnancy 6. Patient already on aspirin 7. Age under 18 years 8. Concurrent participation in another clinical trial
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E.5 End points |
E.5.1 | Primary end point(s) |
The pilot phase of IRELAND is expected to be underpowered to assess efficacy of aspirin on perinatal outcome. This pilot will address uptake, compliance drop-out rates and effect of low-dose aspirin on platelet function in this group. Antiplatelet effect, compared between study (aspirin) and control (no aspirin) groups will be measured using a novel dynamic platelet assay. The biologic effect of low-dose aspirin on platelet function in this population with respect to variables that may affect bioavailability (maternal body mass index, gestational age, compliance) will also be measured.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The pilot phase of IRELAND is expected to be underpowered to assess efficacy of aspirin on perinatal outcome. This pilot will address uptake, compliance drop-out rates and effect of low-dose aspirin on platelet function in this group. Antiplatelet effect, compared between study (aspirin) and control (no aspirin) groups will be measured using a novel dynamic platelet assay. The biologic effect of low-dose aspirin on platelet function in this population with respect to variables that may affect bioavailability (maternal body mass index, gestational age, compliance) will also be measured.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Delivery of last patient recruited |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |