Medical management of severe aortic regurgitation in asymptomatic patients with normal left ventricular function with valsartan -a study to assess disease progression
| ISRCTN | ISRCTN96078487 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN96078487 |
| Secondary identifying numbers | N0265170217 |
- Submission date
- 29/09/2006
- Registration date
- 29/09/2006
- Last edited
- 06/03/2015
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr R Steeds
Scientific
Scientific
Cardiology
Selly Oak Hospital
Birmingham
B29 6JD
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Medical management of severe aortic regurgitation in asymptomatic patients with normal left ventricular function with valsartan -a study to assess disease progression |
| Study objectives | 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(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Valsartan, nifedipine |
| Primary outcome measure | 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 study start date | 10/04/2005 |
| Completion date | 10/04/2008 |
| Reason abandoned (if study stopped) | Participant recruitment issue |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Not Specified |
| Target number of participants | Not provided at time of registration |
| Key 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) |
| Key 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 |
| Date of first enrolment | 10/04/2005 |
| Date of final enrolment | 10/04/2008 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Selly Oak Hospital
Birmingham
B29 6JD
United Kingdom
B29 6JD
United Kingdom
Sponsor information
Record Provided by the NHSTCT Register - 2006 Update - Department of Health
Government
Government
The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
| Phone | +44 (0)207 307 2622 |
|---|---|
| dhmail@doh.gsi.org.uk | |
| Website | http://www.dh.gov.uk/Home/fs/en |
Funders
Funder type
Hospital/treatment centre
University Hospital Birmingham NHS Trust
No information available
NHS R&D Support Funding
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
