Does allopurinol reduce thickening of the left ventricle of the heart in patients with treated hypertension?
| ISRCTN | ISRCTN40476871 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN40476871 |
| EudraCT/CTIS number | 2014-002083-33 |
| ClinicalTrials.gov number | NCT02237339 |
| Secondary identifying numbers | 2012CV15 |
- Submission date
- 10/09/2014
- Registration date
- 03/10/2014
- Last edited
- 22/07/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
People with high blood pressure are at increased risk of heart complications. One of the biggest problems is that the muscle wall of the heart thickens. The medical term for this is left ventricular hypertrophy (LVH). LVH makes the heart work less well less well and patients with LVH are at a 10 times greater risk of heart complications than those without it. A goal of treating high blood pressure is to reduce the strain on the heart and to try to decrease this thickening of the heart wall. However, even when blood pressure is treated and is under control, LVH can persist, and as there are no symptoms some people dont know they have it. Currently the only way to reduce LVH would be to lower blood pressure (BP) even further. This can cause side-effects from low BP such as dizziness and nausea. However, a drug, allopurinol used to treat gout, has been shown to reduce this thickening of the heart wall in patients who had kidney disease or diabetes. We now want to see if patients with high blood pressure and LVH may also benefit from treatment with allopurinol. If LVH can be reduced using allopurinol, this might be a new way to reduce cardiac risk in these patients without needing to lower BP even further.
Who can participate?
People over 18 with high blood pressure and LVH.
What does the study involve?
Participants are first screened for LVH by doing an ultrasound scan of the heart. This diagnosis is confirmed with a Magnetic Resonance Imaging (MRI) scan. This is a special scan of the heart using an MRI machine to measure the extent of thickening of the heart muscle before they start the trial. Participants are then randomly allocated into one of two groups. Those in group 1 are treated with allopurinol for a year. Those in group 2 are given a placebo (dummy pill) for the same time period. All the patients currently prescribed medication for their high blood pressure continue as normal on that. After the years treatment is complete, a second MRI scan of the heart is then done to compare the effects of the allopurinol with that of the placebo.
What are the possible benefits and risks of participating?
Participants are monitored closely during the study and seen by a doctor with a special interest in cardiology at each study visit and their medication will be reviewed on a regular basis. The tests provide information about the function of the heart, kidneys and blood circulation. If any of these investigations, including information from the MRI scan of the heart reveal any new abnormality, this is discussed with the participants hospital consultant to refer them specialist clinic. If the results of the study are positive, it may change how patients with controlled high blood pressure and LVH are managed and it potentially will have a great impact on other such patients in the future. Side effects from taking allopurinol are very rare (less than 1 in 10,000 people) but include headache, stomach upset, drowsiness and anaemia. Having blood tests taken can cause some mild bruising. The flow mediated dilatation may cause temporary numbness. MRI scanning is very safe and does not use radiation but some may feel a bit closed in. The scanner is a bit noisy but participants are given ear protection which also plays music.
Where is the study run from?
Ninewells Hospital & Medical School, Dundee (UK)
When is the study starting and how long is it expected to run for?
September 2014 to July 2017
Who is funding the study?
British Heart Foundation (UK)
Who is the main contact?
Dr Christopher Gingles
c.r.gingles@dundee.ac.uk
Contact information
Scientific
Department of Clinical Pharmacology
Division of Medicine and Therapeutics
Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom
Study information
| Study design | Randomised double-blinded placebo-controlled single-centre study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet: c.r.gingles@dundee.ac.uk |
| Scientific title | Does allopurinol regress left ventricular hypertrophy in patients with treated essential hypertension? |
| Study acronym | ALLAY |
| Study objectives | Does allpourinol causes regression of left ventricular hypertrophy in patients with essential hypertension? |
| Ethics approval(s) | East of Scotland Research Ethics Service, 27/06/2014, ref. 14/ES/0073 |
| Health condition(s) or problem(s) studied | Essential hypertensives with left ventricular hypertrophy |
| Intervention | Treatment arm: Allopurinol 300mg daily for one month then 300mg twice daily for eleven months. Placebo arm: Microcrystalline cellulose one tablet daily for one month then twice daily for eleven months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Allopurinol |
| Primary outcome measure | The change LV mass index with allopurinol versus placebo Timescale: 12 months Description: Baseline and repeat CMRI examinations at baseline (day 0) and after the final (12 month visit) on a 3T Magnetom scanners (Siemens, Erlangen, Germany) using dedicated phase array cardiac coils. Analysis will be performed offline (Argus Software, Siemens) by a single blinded observer for the assessment of left ventricular mass. This single observer will analyse all the scans. The reproducibility of the left ventricular mass assessment using MRI will be derived for this observer. The change LV mass index in participants treated with allopurinol will be compared with placebo. |
| Secondary outcome measures | 1. % change in brachial artery diameter and change in augmentation index with allopurinol versus placebo. Timescale: 12 months. Description: Flow mediated dilatation (FMD) of the brachial artery will be performed on two visits (baseline(day 0 and month 12) according to the guide-lines set by the International Brachial Artery Reactivity Task Force. FMD will be expressed as percent change in diameter relative to the baseline diameter at rest. Analysis of all FMDs will be performed on Brachial Analyser software by a single trained investigator. This investigator will be blind to allocated treatments. PWA and PWV will be determined in the arm by recording the radial waveforms and radial-carotid waveforms, respectively, at two visits (baseline and month 12) using the Sphygmocor system. The central augmentation index (AIx) will be corrected to a heart rate of 75 beats/min. A single trained investigator who is blind to the allocated treatment will perform the PWA and PWV. 2. Change in average 24 hour BP control with allopurinol versus placebo. Timescale: 12 months. Description: Patient will undergo 24 hour ambulatory BP monitoring after the screening and final visit (12 months) to assess the difference in blood pressure control with allopurinol versus placebo. 3. The change in C reactive protein (CRP), brain naturetic peptide (BNP), troponin I (TnI), oxidized lactate dehydrogenase (oxidized LDH) and Procollagen carboxyl end peptide (PICP) with allopurinol versus placebo. Timescale: 12 months. Description: Research bloods will be taken at vist 2 (day 0) and visit 7 (12months) and will compare changes between groups. 4. Measure a change in left ventricular (LV) mass, LV end systolic volume, LV end diastolic volume or LV ejection fraction. Timescale: 12 months. Description: Baseline and repeat CMRI examinations at baseline (+/- 2 weeks) and after the final 12 month (+/- 2 weeks) visit will be performed on a 3T Magnetom scanners (Siemens, Erlangen, Germany) using dedicated phase array cardiac coils. Analysis will be performed offline (Argus Software, Siemens) by a single blinded observer for the assessment of ventricular volumes (EDV, ESV, stroke volume), EF, and left ventricular mass. This single observer will analyse all the scans. The reproducibility of the left ventricular mass assessment using MRI will be derived for this observer. We will assess left ventricular (LV) mass, LV end systolic volume, LV end diastolic volume and LV ejection fraction in participants treated with allopurinol versus placebo. 5. The change in LV mass after subtracting the volume of scar with allopurinol versus placebo. Timescale: 12 months Description: Baseline and repeat CMRI examinations at baseline (+/- 2 weeks) and after the final 12 month (+/- 2 weeks) visit will be performed on a 3T Magnetom scanners (Siemens, Erlangen, Germany) using dedicated phase array cardiac coils. Analysis will be performed offline (Argus Software, Siemens) by a single blinded observer for the assessment of left ventricular mass and scar volume |
| Overall study start date | 09/09/2014 |
| Completion date | 31/07/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 66 |
| Total final enrolment | 72 |
| Key inclusion criteria | 1. Aged over 18 years 2. Previously diagnosed with essential hypertension 3. Been on stable antihypertensive therapy for at least 3 months prior to study screening 4. Have screening ABPM (or home based BP monitoring if ABPM not tolerated) with daytime average systolic <135mmHg or 24-hour average systolic ≤ 130mmHg 5. Have screening echocardiography based diagnosis of LVH based on ASE criteria (males >115g/m2, females >95g/m2) |
| Key exclusion criteria | 1. Documented intolerance to allopurinol 2. Left ventricular ejection fraction <45% on echocardiography screening 3. Severe aortic stenosis on echocardiography screening 4. Already had gout or currently on allopurinol 5. Severe hepatic disease 6. Renal disease; CKD class 3B or worse 7. On azathioprine, 6 mercaptopurine, or theophylline 8. Malignancy (receiving active treatment) or other life threatening diseases 9. Pregnant or lactating women 10. Any contraindication to MRI (claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention) 11. Patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days will be excluded 12. Patients who are unable to give informed consent 13. Any other considered by a study physician to be inappropriate for inclusion |
| Date of first enrolment | 30/09/2014 |
| Date of final enrolment | 31/07/2017 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
DD1 9SY
United Kingdom
Sponsor information
Hospital/treatment centre
c/o Catrina Forde
Tayside Medical Sciences Manager
Ninewells Hospital & Medical School
TASC Research & Development Office
Residency Block, Level 3
George Pirrie Way
Dundee
DD1 9SY
Scotland
United Kingdom
"ROR" |
https://ror.org/03h2bxq36 |
|---|
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Jacob George. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/12/2019 | 22/07/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
22/07/2019: The following changes were made:
1. Publication reference added.
2. The final enrolment number has been added.
27/06/2019: IPD sharing statement added.
25/06/2019: No publications found. Verifying results with principal investigator.
04/01/2019: The NCT number has been added.
06/10/2014: The trial is currently recruiting.
