Clinical trial NCT01278459: Can Atorvastatin Improve Vascular Function in Women With a History of Preeclampsia?
Official title: Can Atorvastatin Improve Vascular Function in Women With a History of Preeclampsia? A Randomised, Double-blinded, Placebo-controlled Crossover Trial of Atorvastatin in Women With a History of Preeclampsia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pre-Eclampsia
Keywords: endothelial function
cardiovascular
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2011-01-17
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to test the hypothesis that a short course of atorvastatin can improve vascular function in women with a history of preeclampsia, compared to placebo.

Detailed description: Women with a history of preeclampsia (high blood pressure/protein in the urine during pregnancy) are at increased risk of developing high blood pressure and heart problems in the 10-15 years after their baby is born. At present we do not know how to reduce this risk. Lowering blood pressure and blood lipid (fats) levels are common strategies for primary prevention of cardiovascular problems. However, most women with a history of preeclampsia in the 5-10 years after pregnancy, will have normal blood pressure readings, blood sugar and cholesterol levels.

Atorvastatin, a type of "statin", is widely used in lowering lipids and preventing cardiovascular disease. This drug has beneficial actions other than lipid-lowering, that may also help prevent cardiovascular problems, including improving function in the lining of blood vessels. We know that impairment in blood vessel function is evident in women in the years after a preeclamptic pregnancy and may contribute to the risk of women after preeclampsia going on to develop cardiovascular disease.

We would like to know if giving a short course of atorvastatin to women with a history of preeclampsia improves their blood vessel function. To do this, ex-preeclamptic women will be invited to take either a atorvastatin or placebo ("dummy") tablet daily for 4 weeks, then no tablets for 4 weeks, then "crossover" to receive the alternative tablet (placebo or atorvastatin) daily for 4 weeks. Blood vessel function would be measured using specialised noninvasive scans and taking a blood test at the beginning and end of each treatment period. The study will be jointly run by the Departments of Cardiovascular Medicine and Obstetrics \& Gynaecology at the John Radcliffe Hospital, Oxford.

We anticipate this study will provide valuable data to support larger clinical trials to determine whether improving blood vessel function ultimately reduces the risk of developing early-onset cardiovascular disease after preeclampsia.

Eligibility criteria: Inclusion Criteria:

* Participant is willing and able to give informed consent for participation in the study.
* 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).
* Participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 4 weeks after.
* Participants must be willing to undertake urine pregnancy test at the start of each 4 week phase of the study to exclude unintended pregnancy.
* Participants must have clinically acceptable laboratory markers of renal, thyroid and hepatic function at enrolment.
* Able (in the Investigator's opinion) and willing to comply with all study requirements.
* Willing to allow her General Practitioner and consultant, if appropriate, to be notified of participation in the study and results of clinical laboratory tests.

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
* Planning to undertake donation of blood during the study.

Primary outcomes:
measure: Alteration in brachial artery flow-mediated dilatation
timeFrame: After 4 weeks treatment with atorvastatin or placebo
Secondary outcomes:
measure: Microvascular endothelial function as measured by laser doppler flowmetry
timeFrame: After 4 weeks treatment with atorvastatin or placebo
measure: Resistance vessel endothelial function as measured by venous occlusion plethysmography
timeFrame: After 4 weeks treatment with atorvastatin or placebo
measure: Indices of arterial stiffness as measured by arterial tonometry and carotid artery distensibility
timeFrame: After 4 weeks treatment with atorvastatin or placebo
measure: Plasma biomarkers of inflammation and endothelial function
timeFrame: After 4 weeks treatment with atorvastatin or placebo
measure: Endothelial glycocalyx as measured by sublingual Microscan
timeFrame: After 4 weeks treatment with atorvastatin or placebo
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: University of Oxford Department of Cardiovascular Medicine
Study officials:
affiliation: University of Oxford
name: Paul Leeson, PhD MRCP FESC
role: PRINCIPAL_INVESTIGATOR
References: