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

Primary Purpose

Pre-Eclampsia

Status
Completed
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Atorvastatin
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pre-Eclampsia focused on measuring endothelial function, cardiovascular

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Oxford Department of Cardiovascular Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Atorvastatin first

Placebo first

Arm Description

Participants receive 4 week treatment with atorvastatin 20mg/day, followed by 4 week washout, followed by 4 week treatment with placebo.

Participants receive 4 week treatment with placebo, followed by 4 weeks washout, followed by 4 weeks treatment with atorvastatin 20mg/day.

Outcomes

Primary Outcome Measures

Alteration in brachial artery flow-mediated dilatation

Secondary Outcome Measures

Microvascular endothelial function as measured by laser doppler flowmetry
Resistance vessel endothelial function as measured by venous occlusion plethysmography
Indices of arterial stiffness as measured by arterial tonometry and carotid artery distensibility
Plasma biomarkers of inflammation and endothelial function
Endothelial glycocalyx as measured by sublingual Microscan

Full Information

First Posted
January 14, 2011
Last Updated
May 29, 2015
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT01278459
Brief Title
Can Atorvastatin Improve Vascular Function in Women With a History of Preeclampsia?
Acronym
PVS3
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

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pre-Eclampsia
Keywords
endothelial function, cardiovascular

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atorvastatin first
Arm Type
Experimental
Arm Description
Participants receive 4 week treatment with atorvastatin 20mg/day, followed by 4 week washout, followed by 4 week treatment with placebo.
Arm Title
Placebo first
Arm Type
Experimental
Arm Description
Participants receive 4 week treatment with placebo, followed by 4 weeks washout, followed by 4 weeks treatment with atorvastatin 20mg/day.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Intervention Description
4 week treatment, 20mg/day taken orally in tablet form
Primary Outcome Measure Information:
Title
Alteration in brachial artery flow-mediated dilatation
Time Frame
After 4 weeks treatment with atorvastatin or placebo
Secondary Outcome Measure Information:
Title
Microvascular endothelial function as measured by laser doppler flowmetry
Time Frame
After 4 weeks treatment with atorvastatin or placebo
Title
Resistance vessel endothelial function as measured by venous occlusion plethysmography
Time Frame
After 4 weeks treatment with atorvastatin or placebo
Title
Indices of arterial stiffness as measured by arterial tonometry and carotid artery distensibility
Time Frame
After 4 weeks treatment with atorvastatin or placebo
Title
Plasma biomarkers of inflammation and endothelial function
Time Frame
After 4 weeks treatment with atorvastatin or placebo
Title
Endothelial glycocalyx as measured by sublingual Microscan
Time Frame
After 4 weeks treatment with atorvastatin or placebo

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Leeson, PhD MRCP FESC
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oxford Department of Cardiovascular Medicine
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom

12. IPD Sharing Statement

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

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