E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cardiovascular disease in women with a history of preeclampsia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047063 |
E.1.2 | Term | Vascular disorder peripheral |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 |
Preeclampsia is a condition unique to pregnancy characterised by high blood pressure and protein in the urine during pregnancy. It affects 3-5% of pregnancies. There is evidence of persistent abnormalities in the lining of a mother's blood vessels (called the "endothelium") after a preeclamptic pregnancy and women with a history of preeclampsia are at increased risk of developing cardiovascular disease in the 10 to 15 years following an affected pregnancy. Few of these women will have values of lipids, blood pressure or glucose that exceed intervention levels according to current clinical guidelines. There is a need to identify alternative approaches to primary prevention for these women. Our aim is to develop novel strategies to reduce risk of future cardiovascular disease in this important group of mothers. Atorvastatin is a drug that is used widely in the primary prevention of heart attack, stroke or angina in people who have multiple risk factors for cardiovascular diseas |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of our study are: 1. To determine possible effects of atorvastatin 20mg/day on additional markers of cardiovascular risk in women with a history of preeclampsia, specifically assessing: • Endothelial function in small vessels (“microvasculature”) • Endothelial function in resistance-sized arteries • Arterial stiffness • Lipid profile • Blood markers of inflammation and endothelial function 2. To assess the effect of atorvastatin on excretion of protein into urine (microalbinuria) and to assess safety and tolerability of atorvastatin 20mg/day in women with previous preeclampsia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participant must • be willing and able to give informed consent for participation in the study. • female, aged 18 -50 years • have been diagnosed with preeclampsia during index pregnancy: defined as (1) new onset hypertension (>140/90 mmHg) after 20 weeks gestation and (2) proteinuria (>0.3g protein/24 hours) [ISSHP Definition] • be willing, if of child bearing potential, to ensure that they or their partner use effective contraception during the study and for 4 weeks after, as defined in ICH (M3) (i.e. methods of birth control which result in a low failure rate of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner) • be willing to undertake urine pregnancy test at the start of each 4 week phase of the study to exclude unintended pregnancy. • have clinically acceptable laboratory markers of renal, thyroid and hepatic function at enrolment. •be able (in the Investigator’s opinion) and willing to comply with all study requirements. •be willing to allow her General Practitioner and consultant, if appropriate, to be notified of participation in the study and results of clinical laboratory tests. |
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E.4 | Principal exclusion criteria |
Participants must NOT be •Pregnant, lactating during the course of the study. •Planning pregnancy during course of study or in 4 weeks after study completion •Taking other medication, whether prescribed or over-the-counter, in the four weeks before first study dose and during the study other than for example mild analgesia or hormonal contraception. •Taking vitamin medications that may interact with atorvastatin (e.g. niacin, Vitamin D) •Terminally ill or is inappropriate for placebo medication Participants must NOT have •Significant renal or hepatic impairment •Significant cardiovascular disease, diabetes mellitus or would have clinical indication(s) for receiving statin therapy (Framingham Risk Score >20%) •Scheduled elective surgery or other procedures requiring general anaesthesia during the study. •Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be alteration in brachial artery flow-mediated dilatation following atorvastatin treatment compared with placebo in women with a history of preeclampsia. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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Investigators will conduct a telephone contact with the participant 4-6 weeks after the final study visit and last dose of study medication to enquire about overall health and to document any changes or possible adverse effects/reactions. The end of the trial will be when all participants have completed the end of study phone call. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 28 |