HypertensionPhase 4ALLAYNCT02237339
Does Allopurinol Reduce Thickening of the Left Ventricle of the Heart in Patient With Treated Hypertension?
A Phase 4 study testing Allopurinol in people with Hypertension and Hypertrophy, Left Ventricular, run by University of Dundee at 1 site in United Kingdom.
Trial summary
The presence of Left ventricular hypertrophy (LVH) confers high cardiovascular risk in hypertensive patients. LVH remains highly prevalent even when blood pressure (BP) is controlled. There is increasing evidence that a major non-haemodynamic contributor to LVH is oxidative stress. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension, Hypertrophy, Left Ventricular
- What is being tested?
- Allopurinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2014to Jun 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- are aged over 18 years
- previously diagnosed with essential hypertension
- been on stable antihypertensive therapy for at least 3 months prior to study screening
- have screening ambulatory bloods pressure monitoring (ABPM) or home based BP monitoring if ABPM not tolerated with daytime average systolic <135mmHg
- have screening echocardiography based diagnosis of left ventricular hypertrophy (LVH) based on American society of echocardiography (ASE) criteria (males >115g/m2, females >95g/m2)
Who cannot join
- documented intolerance to allopurinol
- left Ventricular Ejection Fraction <45% on echocardiography screening
- severe aortic stenosis on echocardiography screening
- active gout (i.e. flare within two years) or currently on allopurinol
- severe hepatic disease
- renal disease; chronic kidney disease (CKD) class 3B or worse
Show all 13Show fewer
- on azathioprine, 6 mercaptopurine, or theophylline
- malignancy (receiving active treatment) or other life threatening diseases
- pregnant or lactating women
- any contraindication to magnetic resonance imaging (MRI) (claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention).
- patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days will be excluded.
- patients who are unable to give informed consent
- any other considered by a study physician to be inappropriate for inclusion.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Dundee, Ninewells Hospital
Dundee, Tayside, DD1 9SY
About this study
Official title: Does Allopurinol Regress Left Ventricular Hypertrophy in Patients With Treated Essential Hypertension?
The presence of Left ventricular hypertrophy (LVH) confers high cardiovascular risk in hypertensive patients. LVH remains highly prevalent even when blood pressure (BP) is controlled. There is increasing evidence that a major non-haemodynamic contributor to LVH is oxidative stress. Allopurinol is known to markedly reduce oxidative stress.
This pragmatic randomised double blind placebo controlled trial will examine whether allopurinol (300 mg bd) regresses LV mass as assessed by cardiac magnetic resonance (CMR) in 66 patients with treated hypertension but who have persisting LVH.
Endothelial and vascular function will also be assessed via flow mediated dilatation (FMD) and pulse wave analysis respectively (PWA) and plasma biomarkers of oxidative stress will be measured. The treatment (allopurinol or placebo) will last 12 months.
Read the detailed description
Does Allopurinol regress Left Ventricular Hypertrophy in Patients with Treated Essential Hypertension?
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 less efficient 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 to LVH it can go undetected.
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.
It has previously been shown that a drug allopurinol, which is usually used to treat gout had the remarkable side effect of being able to reduce this thickening of the heart wall in patients who had kidney disease or diabetes. The aim now is 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.
In this study the aim is to recruit 66 patients who have treated and well controlled blood pressure but may still have LVH. They will be screened for LVH by doing an ultrasound scan of the heart and then that will be confirmed with a Magnetic Resonance Imaging (MRI) scan, which is a special scan of the heart using an MRI machine to measure the extent of thickening of the heart muscle before they start on treatment of allopurinol or placebo.
As this is a clinical trial the participants will be randomly allocated to either allopurinol or a dummy medication (placebo) and will receive one year of treatment so that the investigators can compare if there is a difference between normal treatment and addition of allopurinol. All the patients currently prescribed medication for their high blood pressure will continue as normal on that. They will have a further MRI scan when their one year treatment with allopurinol or placebo finishes.
Benefits - You will be monitored closely during the study and will be seen by a doctor with a special interest in cardiology at each of your study visits and your medication will be reviewed on a regular basis. The tests will give us information about the function of your heart, kidneys and blood circulation. If any of these investigations, including information from the MRI scan of your heart reveal any new abnormality we will either discuss this with your hospital consultant or refer you to a specialist clinic (whichever seems most appropriate). The study will not immediately benefit you, but if the results of the study are positive it may change the practice of managing patients with treated high blood pressure but may still have LVH, like you and potentially will have a great impact on other such patients in the future. If so, you may gain eventually from our discovering a new treatment for your condition.
Risks - The side effects of the allopurinol are very rare (less than 1 in 10,000 people) and 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 you will be given ear protection which also plays music. Your kidney function will be assessed before the scan to ensure it is safe to give you the contrast agent described above.
- Conditions
- Hypertension, Hypertrophy, Left Ventricular
- Being tested
- Allopurinol, Placebo
- Keywords
- Allopurinol, Cardiac MRI (CMR), Flow mediated dilatation (FMD), Pulse wave analysis (PWA), Endothelial function, Scar, Hypertrophy, Hypertension
- Medical subject headings
- Hypertension, Hypertrophy, Left Ventricular, Cicatrix, Hypertrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopurinolDrug
Also called Zyloric
Uric acid lowering medication.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Allopurinol | Active comparator | Patients treated with Allopurinol 300mg daily for first month then 300mg twice daily for remainder trial. Receives: Drug: Allopurinol |
| Placebo tablet | Placebo comparator | Microcrystalline cellulose one tablet daily for first month then twice daily for remainder of trial. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change LV mass index with allopurinol versus placebo.
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. This single observer will analyze 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.
Measured: 12 months
Secondary outcomes (5)
% change in brachial artery diameter and change in augmentation index with allopurinol versus placebo.
Flow mediated dilatation (FMD) of the brachial artery will be performed on two visits (baseline 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.
Measured: 12 months
Change in average 24 hour BP control with allopurinol versus placebo.
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.
Measured: 12 months
The change in C reactive protein (CRP), brain natriuretic peptide (BNP), troponin I (TnI), oxidized lactate dehydrogenase (oxidized LDH) and Procollagen carboxyl end peptide (PICP) with allopurinol versus placebo.
Research bloods will be taken at vist 2 (day 0) and visit 7 (12months) and will compare changes between groups.
Measured: 12 months
Measure a change in left ventricular (LV) mass, LV end systolic volume, LV end diastolic volume or LV ejection fraction.
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 analyze 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.
Measured: Twelve months
The change in LV mass after subtracting the volume of scar with allopurinol versus placebo.
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Sponsor
- Investigators
- Christopher Gingles, MBChB, Principal investigator, University of DundeeJacob George, MBChB, Study director, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02237339
- Sponsor's protocol ID
- 2012CV15
- Other IDs
- 2014-002083-33, 2014
- Acronym
- ALLAY
- Status last verified
- Sep 2019
- First submitted
- 18 Aug 2014
- Last updated
- 17 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gingles CR, Symon R, Gandy SJ, Struthers AD, Houston G, MacDonald TM, Lang CC, Donnan PT, George J. Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension. J Hypertens. 2019 Dec;37(12):2481-2489. doi: 10.1097/HJH.0000000000002189.
PubMed 31268872
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Allopurinol Regress Left Ventricular Hypertrophy in Patients With Treated Essential Hypertension?
- ClinicalTrials.gov ID
- NCT02237339
- Acronym / sponsor ID
- ALLAY / 2012CV15
- Conditions
- Hypertension, Hypertrophy, Left Ventricular
- Keywords
- Allopurinol, Cardiac MRI (CMR), Flow mediated dilatation (FMD), Pulse wave analysis (PWA), Endothelial function, Scar, Hypertrophy, Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- Sep 2014 (actual)
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 11 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The presence of Left ventricular hypertrophy (LVH) confers high cardiovascular risk in hypertensive patients. LVH remains highly prevalent even when blood pressure (BP) is controlled. There is increasing evidence that a major non-haemodynamic contributor to LVH is oxidative stress. Allopurinol is known to markedly reduce oxidative stress.
This pragmatic randomised double blind placebo controlled trial will examine whether allopurinol (300 mg bd) regresses LV mass as assessed by cardiac magnetic resonance (CMR) in 66 patients with treated hypertension but who have persisting LVH.
Endothelial and vascular function will also be assessed via flow mediated dilatation (FMD) and pulse wave analysis respectively (PWA) and plasma biomarkers of oxidative stress will be measured. The treatment (allopurinol or placebo) will last 12 months.
Detailed description
Does Allopurinol regress Left Ventricular Hypertrophy in Patients with Treated Essential Hypertension?
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 less efficient 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 to LVH it can go undetected.
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.
It has previously been shown that a drug allopurinol, which is usually used to treat gout had the remarkable side effect of being able to reduce this thickening of the heart wall in patients who had kidney disease or diabetes. The aim now is 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.
In this study the aim is to recruit 66 patients who have treated and well controlled blood pressure but may still have LVH. They will be screened for LVH by doing an ultrasound scan of the heart and then that will be confirmed with a Magnetic Resonance Imaging (MRI) scan, which is a special scan of the heart using an MRI machine to measure the extent of thickening of the heart muscle before they start on treatment of allopurinol or placebo.
As this is a clinical trial the participants will be randomly allocated to either allopurinol or a dummy medication (placebo) and will receive one year of treatment so that the investigators can compare if there is a difference between normal treatment and addition of allopurinol. All the patients currently prescribed medication for their high blood pressure will continue as normal on that. They will have a further MRI scan when their one year treatment with allopurinol or placebo finishes.
Benefits - You will be monitored closely during the study and will be seen by a doctor with a special interest in cardiology at each of your study visits and your medication will be reviewed on a regular basis. The tests will give us information about the function of your heart, kidneys and blood circulation. If any of these investigations, including information from the MRI scan of your heart reveal any new abnormality we will either discuss this with your hospital consultant or refer you to a specialist clinic (whichever seems most appropriate). The study will not immediately benefit you, but if the results of the study are positive it may change the practice of managing patients with treated high blood pressure but may still have LVH, like you and potentially will have a great impact on other such patients in the future. If so, you may gain eventually from our discovering a new treatment for your condition.
Risks - The side effects of the allopurinol are very rare (less than 1 in 10,000 people) and 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 you will be given ear protection which also plays music. Your kidney function will be assessed before the scan to ensure it is safe to give you the contrast agent described above.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allopurinol | Active comparator | Drug: AllopurinolPatients treated with Allopurinol 300mg daily for first month then 300mg twice daily for remainder trial. |
| Placebo tablet | Placebo comparator | Drug: PlaceboMicrocrystalline cellulose one tablet daily for first month then twice daily for remainder of trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- are aged over 18 years
- previously diagnosed with essential hypertension
- been on stable antihypertensive therapy for at least 3 months prior to study screening
- have screening ambulatory bloods pressure monitoring (ABPM) or home based BP monitoring if ABPM not tolerated with daytime average systolic <135mmHg
- have screening echocardiography based diagnosis of left ventricular hypertrophy (LVH) based on American society of echocardiography (ASE) criteria (males >115g/m2, females >95g/m2)
Key exclusion criteria (13 listed)
- documented intolerance to allopurinol
- left Ventricular Ejection Fraction <45% on echocardiography screening
- severe aortic stenosis on echocardiography screening
- active gout (i.e. flare within two years) or currently on allopurinol
- severe hepatic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AllopurinolAlso: ZyloricUric acid lowering medication. | Drug | Allopurinol |
| Placebo | Drug | Placebo tablet |
Primary outcome
The change LV mass index with allopurinol versus placebo.
Time frame: 12 months
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. This single observer will analyze 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.
5 secondary outcomes
% change in brachial artery diameter and change in augmentation index with allopurinol versus placebo.
Time frame: 12 months
Change in average 24 hour BP control with allopurinol versus placebo.
Time frame: 12 months
The change in C reactive protein (CRP), brain natriuretic peptide (BNP), troponin I (TnI), oxidized lactate dehydrogenase (oxidized LDH) and Procollagen carboxyl end peptide (PICP) with allopurinol versus placebo.
Time frame: 12 months
Measure a change in left ventricular (LV) mass, LV end systolic volume, LV end diastolic volume or LV ejection fraction.
Time frame: Twelve months
The change in LV mass after subtracting the volume of scar with allopurinol versus placebo.
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Derived from this study: PubMed 31268872Gingles CR, Symon R, Gandy SJ, Struthers AD, Houston G, MacDonald TM, Lang CC, Donnan PT, George J. Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension. J Hypertens. 2019 Dec;37(12):2481-2489. doi: 10.1097/HJH.0000000000002189.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Gingles, MBChB principal investigator
University of Dundee
Jacob George, MBChB study director
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Allopurinol in people with Hypertension and Hypertrophy, Left Ventricular, run by University of Dundee at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change LV mass index with allopurinol versus placebo. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02237339, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.