Plain English Summary
Background and study aims
Aortic stenosis is a serious heart condition with no known means of prevention. It is caused by the build up of calcium (a mineral found in the blood) on the aortic valve (flaps of tissue which regulates blood flow) leading to obstruction of blood flow from the heart. Death follows symptoms of heart failure in most cases unless the valve is surgically replaced. The aim of this study is to determine the effect of the drug sevelamer on blood phosphate levels with a view to using this in the prevention of aortic stenosis.
Who can participate?
Adults aged 18 to 90 with mild to moderate aortic stenosis
What does the study involve?
All participants have two periods taking sevelamer (a different dose in each period) and a period taking a placebo (a dummy pill), each period lasting 6 weeks (18 weeks overall). The sequence of treatments and placebo is allocated at random. Blood and urine phosphate levels are measured at the end of each period.
What are the possible benefits and risks of participating?
This study is the first step in determining whether the progression of aortic stenosis can be prevented using sevelamer. This will help guide future medical practice both in the management of the aortic stenosis of patients participating in the study and other people with the same condition. Some people may experience side effects which are reversible on stopping treatment. These tend to be symptoms affecting the gut such as abdominal discomfort, belching, bloating, constipation, diarrhea, and feeling of fullness after eating. Major side effects are extremely rare.
Where is the study run from?
The Wolfson Institute of Preventive Medicine in London is the coordinating centre for the study where all study-related activities take place once patients have given their consent to be in the study. Patients are initially identified from two hospitals: St Bartholomew’s Hospital and St Thomas’ Hospital (UK)
When is the study starting and how long is it expected to run for?
June 2017 to September 2018
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Professor David Wald
Trial website
Additional identifiers
EudraCT number
2015-000704-25
ClinicalTrials.gov number
Protocol/serial number
PAS01
Study information
Scientific title
Prevention of Aortic Stenosis pilot trial: a randomised cross-over trial
Acronym
PAS Pilot Trial
Study hypothesis
The aim of this study is to assess the efficacy of sevelamer in lowering serum phosphate in patients with aortic stenosis.
Ethics approval
Westminster Research Ethics Committee, 24/02/2017, ref: 17/LO/0120
Study design
Randomised placebo-controlled double blind cross-over trial
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Aortic stenosis
Intervention
All participants in the study will have two periods taking sevelamer (a different dose in each period) and a period taking a placebo (a dummy pill), each period lasting six weeks (18 weeks overall). The sequence of treatments and placebo will be allocated at random. There are no off-treatment washout periods because the treatment period (6 weeks) is long enough for the effect of the previous treatment to have washed out by the end of each treatment period.
1. 800mg sevelamer three times a day (low dose)
2. 2.4g sevelamer three times a day (standard dose)
3. Placebo three times a day
Intervention type
Drug
Phase
Phase II
Drug names
Sevelamer
Primary outcome measure
Serum phosphate, measured using standard methods for lab analysis at baseline, 6, 12 and 18 weeks
Secondary outcome measures
Urine phosphate, measured using standard methods for lab analysis at 6, 12 and 18 weeks
Overall trial start date
15/06/2017
Overall trial end date
15/09/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aortic stenosis (Vmax 2.0-4.0 m/s)
2. Age 18-90
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
54-72
Total final enrolment
72
Participant exclusion criteria
1. Contraindications, including a history of allergy to sevelamer, a history of hypophosphataemia or a history of bowel obstruction
2. A requirement for phosphate binding drugs for other reasons
3. A requirement for drugs that interact with phosphate binding drugs
4. A history of lactose intolerance
5. Any illness judged to contra-indicate participation in the trial
6. Pregnant or breastfeeding women
Recruitment start date
15/06/2017
Recruitment end date
15/06/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Wolfson Institute of Preventive Medicine
Charterhouse Square
London
EC1M 6BQ
United Kingdom
Trial participating centre
St Bartholomew's Hospital
West Smithfield
London
EC1A 7BE
United Kingdom
Trial participating centre
St Thomas' Hospital
Westminster Bridge Road
Lambeth
London
SE1 7EH
United Kingdom
Funders
Funder type
Research council
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Plan is to publish in a peer-reviewed journal around one year from end of trial.
IPD sharing statement
Pseudoanonymised trial data stored in secure Safe Haven repository at Centre for Environmental and Preventive Medicine. Data requests to Prof. David Wald (custodian).
Intention to publish date
15/09/2019
Participant level data
Stored in repository
Basic results (scientific)
Publication list
2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/31500854 (added 12/09/2019)