Can Atorvastatin Improve Vascular Function in Women With a History of Preeclampsia? (PVS3)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01278459
First received: January 14, 2011
Last updated: November 10, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Pre-Eclampsia
Drug: Atorvastatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
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.

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Alteration in brachial artery flow-mediated dilatation [ Time Frame: After 4 weeks treatment with atorvastatin or placebo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Microvascular endothelial function as measured by laser doppler flowmetry [ Time Frame: After 4 weeks treatment with atorvastatin or placebo ] [ Designated as safety issue: No ]
  • Resistance vessel endothelial function as measured by venous occlusion plethysmography [ Time Frame: After 4 weeks treatment with atorvastatin or placebo ] [ Designated as safety issue: No ]
  • Indices of arterial stiffness as measured by arterial tonometry and carotid artery distensibility [ Time Frame: After 4 weeks treatment with atorvastatin or placebo ] [ Designated as safety issue: No ]
  • Plasma biomarkers of inflammation and endothelial function [ Time Frame: After 4 weeks treatment with atorvastatin or placebo ] [ Designated as safety issue: No ]
  • Endothelial glycocalyx as measured by sublingual Microscan [ Time Frame: After 4 weeks treatment with atorvastatin or placebo ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2011
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin first
Participants receive 4 week treatment with atorvastatin 20mg/day, followed by 4 week washout, followed by 4 week treatment with placebo.
Drug: Atorvastatin
4 week treatment, 20mg/day taken orally in tablet form
Experimental: Placebo first
Participants receive 4 week treatment with placebo, followed by 4 weeks washout, followed by 4 weeks treatment with atorvastatin 20mg/day.
Drug: Atorvastatin
4 week treatment, 20mg/day taken orally in tablet form

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01278459

Locations
United Kingdom
University of Oxford Department of Cardiovascular Medicine
Oxford, United Kingdom, OX3 9DU
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Paul Leeson, PhD MRCP FESC University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01278459     History of Changes
Other Study ID Numbers: 2008-005759-21
Study First Received: January 14, 2011
Last Updated: November 10, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
endothelial function
cardiovascular

Additional relevant MeSH terms:
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014