Condition category
Circulatory System
Date applied
29/09/2006
Date assigned
29/09/2006
Last edited
06/03/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr R Steeds

ORCID ID

Contact details

Cardiology
Selly Oak Hospital
Birmingham
B29 6JD
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0265170217

Study information

Scientific title

Medical management of severe aortic regurgitation in asymptomatic patients with normal left ventricular function with valsartan -a study to assess disease progression

Acronym

Study hypothesis

Treatment with valsartan reduces the adaptive increase in LV mass to chronic moderate-severe AR in asymptomatic patients (NYHA II or less) with normal EF >50% and preserved LV dimensions (LVIDs less than 5.5cm) to a greater extent than short-acting nifedipine.

Updated 06/03/2015: the trial was stopped due to lack of recruitment.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Cardiovascular: Severe Aortic Regurgitation

Intervention

Patients will be randomised in a single blind fashion to Valsartan 80 mg twice daily or modified release nifedipine 20 mg bd continued for one year.

In all patients at entry, a full clinical assessment will be performed and clinical details including cause of AR, presence of vascular disease, risk factors for vascular disease and drug therapy will be recorded. Blood pressure, heart rate and body mass index will be recorded. NYHA and CSA status will be recorded. A 12 lead ECG will be recorded. Routine haematological and biochemical parameters including plasma lipids will be recorded. Renal function will be measured at two weeks following randomisation. If creatinine has risen by more that 10% or >150 micromol/l or potassium >5.9 mmol/l then the study drug will be withdrawn. Exercise capacity will be assessed using the six minute walk test. At baseline, the following measurements will be made:

CMR
LV mass, LV volumes and LV function will be calculated using serial contiguous short axis TrueFISP cine sequences with 7 mm slice thickness and 3 mm gap using a 1.5-Tesla magnet as previously described (Bellenger and Pennell 2002). Analysis will be performed off-line using the semi-automated Siemens ARGOS software. In addition, regurgitant fraction and regurgitant volumes will be calculated from LV and RV volumetric analysis, together with velocity-encoded flow mapping.

ECHOCARDIOGRAPHY
The following parameters will be obtained:
Assessment of AR:
- Regurgitant jet size on CF Doppler (%LVOT)
- Vena contracta
- PISA radius and effective orifice quantification
- Diastolic jet deceleration (pressure half-time)
- Regurgitant fraction by stroke volume (AV / PV)
- Doppler flow reversal aorta
- Subjective assessment
LV mass (ASE): 0.80 . 1.05 . [(IVS+PW+LVID)3 - LVID3]
LV systolic (and diastolic) function:
- LVEF by modified Simpsons rule
- Tei index

REPEATED MEASURES
Clinical, biochemical, echo and CMR assessment will be repeated at 12 months.

Intervention type

Drug

Phase

Not Applicable

Drug names

Valsartan, nifedipine

Primary outcome measures

The primary end-point will be a comparison in the reduction in LV mass assessed with cardiac MR at one year between Valsartan 80mg bd and modified release nifedipine 20mg bd.

Quality of measurement will be enhanced by assessment by two independent assessors at different sittings. Studies will be performed to confirm inter- and intra-observer variability of assessments.

Secondary outcome measures

1. Change in LV ejection fraction
2. Change in LV volume
3. Change in regurgitant fraction
4. Reduction in progression to the combined end-point of symptoms (NYHA >II)
5. LV systolic dysfunction (LVEF<50%)
6. Requirement for AVR
6. Death over the study period

Overall trial start date

10/04/2005

Overall trial end date

10/04/2008

Reason abandoned

Participant recruitment issue

Eligibility

Participant inclusion criteria

Subjects are to be recruited from patients either under active follow-up or active referral as in-patients or out-patients to the Department of Cardiology, University Hospital Birmingham. Inclusion criteria:
1. Asymptomatic or mildly symptomatic patients with moderate - severe AR (NYHA II or less; CSA <2)
2. Normal LVEF >50%
3. Preserved LV dimensions (LVIDs <5.5cm)

Participant type

Patient

Age group

Not Specified

Gender

Not Specified

Target number of participants

Not provided at time of registration

Participant exclusion criteria

1. Acute, severe AR or rapid deterioration of AR (within the preceding six months)
2. Mixed aortic stenosis and regurgitation (valve stenosis > mild defined as peak gradient above 20 mm Hg)
3. Evidence of additional valvular or congenital heart disease on echocardiographic study sufficient to require surgical intervention
4. Abnormal left ventricular ejection fraction (<50 percent)
5. Contra-indications to Angiotensin II receptor antagonist therapy (previous intolerance; known or suspected renovascular hypertension; creatinine >150 umol/L, serum potassium > 5.9 mmol/l) or to treatment with nifedipine
6. Contra-indication to cardiac MRI

Recruitment start date

10/04/2005

Recruitment end date

10/04/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Selly Oak Hospital
Birmingham
B29 6JD
United Kingdom

Sponsor information

Organisation

Record Provided by the NHSTCT Register - 2006 Update - Department of Health

Sponsor details

The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)207 307 2622
dhmail@doh.gsi.org.uk

Sponsor type

Government

Website

http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Hospital/treatment centre

Funder name

University Hospital Birmingham NHS Trust

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

NHS R&D Support Funding

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes