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Does Allopurinol Reduce Thickening of the Left Ventricle of the Heart in Patient With Treated Hypertension? (ALLAY)

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ClinicalTrials.gov Identifier: NCT02237339
Recruitment Status : Completed
First Posted : September 11, 2014
Last Update Posted : November 1, 2017
Sponsor:
Collaborator:
British Heart Foundation
Information provided by (Responsible Party):
Dr Christopher Gingles, University of Dundee

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Hypertension Hypertrophy, Left Ventricular Drug: Allopurinol Drug: Placebo Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Allopurinol Regress Left Ventricular Hypertrophy in Patients With Treated Essential Hypertension?
Actual Study Start Date : September 2014
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Allopurinol
Patients treated with Allopurinol 300mg daily for first month then 300mg twice daily for remainder trial.
Drug: Allopurinol
Uric acid lowering medication.
Other Name: Zyloric

Placebo Comparator: Placebo tablet
Microcrystalline cellulose one tablet daily for first month then twice daily for remainder of trial.
Drug: Placebo



Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. % change in brachial artery diameter and change in augmentation index with allopurinol versus placebo. [ Time Frame: 12 months ]

    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.


  2. Change in average 24 hour BP control with allopurinol versus placebo. [ Time Frame: 12 months ]
    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 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 ]
    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. [ Time Frame: Twelve 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 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.


  5. The change in LV mass after subtracting the volume of scar 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 and scar volume.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02237339


Locations
United Kingdom
University of Dundee, Ninewells Hospital
Dundee, Tayside, United Kingdom, DD1 9SY
Sponsors and Collaborators
University of Dundee
British Heart Foundation
Investigators
Principal Investigator: Christopher Gingles, MBChB University of Dundee
Study Director: Jacob George, MBChB University of Dundee

Responsible Party: Dr Christopher Gingles, Research Fellow/Principal investigator., University of Dundee
ClinicalTrials.gov Identifier: NCT02237339     History of Changes
Other Study ID Numbers: 2012CV15
2014-002083-33 ( EudraCT Number )
First Posted: September 11, 2014    Key Record Dates
Last Update Posted: November 1, 2017
Last Verified: October 2017

Keywords provided by Dr Christopher Gingles, University of Dundee:
Allopurinol
Cardiac MRI (CMR)
Flow mediated dilatation (FMD)
Pulse wave analysis (PWA)
Endothelial function
Scar
Hypertrophy
Hypertension

Additional relevant MeSH terms:
Hypertension
Hypertrophy
Hypertrophy, Left Ventricular
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Cardiomegaly
Heart Diseases
Allopurinol
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs