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

NCT02237339 | Completed Phase 4 DMC

• 2 other identifiers: 2012CV152014-002083-33
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension; Hypertrophy, Left Ventricular

Keywords

Allopurinol; Cardiac MRI (CMR); Flow mediated dilatation (FMD); Pulse wave analysis (PWA); Endothelial function; Scar; Hypertrophy; Hypertension

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (5)

• % change in brachial artery diameter and change in augmentation index with allopurinol versus placebo.

  12 months

• Change in average 24 hour BP control with allopurinol versus placebo.

  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.

  12 months

• Measure a change in left ventricular (LV) mass, LV end systolic volume, LV end diastolic volume or LV ejection fraction.

  Twelve months

• The change in LV mass after subtracting the volume of scar with allopurinol versus placebo.

  12 months

Study Arms (2)

Allopurinol

ACTIVE COMPARATOR

Patients treated with Allopurinol 300mg daily for first month then 300mg twice daily for remainder trial.

Drug: Allopurinol

Placebo tablet

PLACEBO COMPARATOR

Microcrystalline cellulose one tablet daily for first month then twice daily for remainder of trial.

Drug: Placebo

Interventions

Allopurinol DRUG

Uric acid lowering medication.

Also known as: Zyloric

Allopurinol

Placebo DRUG

Placebo tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Dundee: lead
• British Heart Foundation: collaborator

Study Sites (1)

University of Dundee, Ninewells Hospital

Dundee, Tayside, DD1 9SY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31268872 DERIVED

MeSH Terms

Conditions

Hypertension; Hypertrophy, Left Ventricular; Cicatrix; Hypertrophy

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cardiomegaly; Heart Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Fibrosis; Pathologic Processes

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Christopher Gingles, MBChB

  University of Dundee

  PRINCIPAL INVESTIGATOR

• Jacob George, MBChB

  University of Dundee

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2014
• First Posted: September 11, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: September 17, 2019

Record last verified: 2019-09

Locations

GB (1)