High Dose (mg) (verinurad/allopurinol) Step 1 - titration_ 3/100 Step 2 - titration_ 7.5/200 Step 3 - target dose_ 12/300

Intermediate Dose (mg) verinurad/allopurinol Step 1 - titration_ 3/100 Step 2 - titration_ 7.5/200 Step 3 - target dose_ 7.5/300

Low Dose (mg) verinurad/allopurinol Step 1 - titration_3/100 Step 2 - titration_3/200 Step 3 - target dose_3/300

Step 1 - titration_0/100 Step 2 - titration_0/200 Step 3 - target dose_0/300

Chronic Kidney Disease

Study treatments will be titrated in 3 steps for target low dose (3 mg), intermediate dose ( 7.5 mg) and High Dose (12 mg) Verinurad.

Verinurad

Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol

Allopurinol

Placebo for Verinurad

Placebo for Allopurinol

Research Site

A Study of Verinurad and Allopurinol in Patients With Chronic Kidney Disease and Hyperuricaemia

A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled Study of Verinurad and Allopurinol in Patients With Chronic KIdney Disease and Hyperuricaemia

urinary albumin to creatinine ratio (UACR).

Change from baseline in estimated glomerular filtration rate

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca

Individuals will receive a once daily dose of dietary nitrate in the form of a beetroot juice concentrate (70mL) containing ~5-6mmol inorganic nitrate (James White Drinks, UK) for 12 +/- 2 weeks. This dose has been chosen due to several reports demonstrating efficacy in patients with cardiovascular disease.

The placebo control is an identical juice from which the nitrate anion has been removed using a standard anion exchange resin. Visually there is no detectable difference between the juices and previous spectral, ion concentration, sugar levels, ascorbate analysis and taste testing has confirmed no differences in colour and constituents. The process to extract nitrate from the juice is the same technique used to remove inorganic nitrate from general drinking water supplies, and has been approved for use by Ethics Committees. The nitrate-free juice is not considered a drug or medicine, and is classified as a foodstuff.

Heart Failure

Heart Failure, Systolic

The beetroot juice contains approximately 100kcal per 100mL of juice, equivalent to a glass of orange juice; the volume of juice per day for the study is 70mL. Volunteers will be informed that an average woman weighing 65kg should not consume more than 2000kcal per day, and an average man of 75kg not more than 2500kcal per day.

Nitrate-rich Beetroot Juice

Nitrate-deplete Beetroot Juice

Queen Mary University of London

Effect of Dietary Nitrate Ingestion in Heart Failure

Investigation of Dietary Nitrate Optimisation by Hyperuricaemia Stratification in Heart Failure

Uric acid is a prognostic marker in patients with heart failure. The intervention proposed acts on the enzyme, xanthine oxidoreductase (XOR), that produces uric acid. We will therefore measure the change in serum uric acid level from baseline to assess whether dietary nitrate treatment decreases hyperuricaemia. We will stratify uric acid levels and undertake analysis between strata.

We will measure the change in nitrate levels in plasma using ozone chemiluminescence, which measures the consumed dose of inorganic nitrate consumed, as the first step in the enterosalivary circuit.

We will measure the change in nitrite levels in plasma using ozone chemiluminescence, measuring the conversion of nitrate to nitrite which the enzyme XOR uses to form the biologically active metabolite, nitric oxide.

We will measure the change in cGMP levels using an ELISA assay, as a stable and measurable surrogate of the biologically active product, nitric oxide.

Using cardiac magnetic resonance imaging (cardiac MRI), we will measure the change in left ventricular ejection fraction from baseline following intervention.

Measured using ELISA and used collectively with oxidised LDL and TBAR assays to determine oxidative stress

Measured using ELISA and used collectively with MDA and TBAR assays to determine oxidative stress

Measured using ELISA and used collectively with oxidised LDL and MDA assays to determine oxidative stress

We will measure expression and activity of XOR by red blood cells, as a marker of both nitrite reductase capacity as well as hyperuricaemia.

Analysis of 24-hour blood pressure monitoring

Analysis of this important natriuretic peptide

Analysis of the highly sensitive marker of inflammation

Measurement of cardiac ventricular function using cardiac MRI (ejection fraction)

Measurement of cardiac ventricular volumes using cardiac MRI

Assessment of heart failure aetiology as measured by late gadolinium enhancement on cardiac MRI

As determined by electrocardiogram analysis

Functional assessment of exercise capacity

All results will be stratified by the pre-existing diagnosis of Type II Diabetes Mellitus to determine whether this additional cause of oxidative stress impacts on the ability of inorganic nitrate to recover function in patients with heart failure

Pre-specified sub-group analyses by dental disease

Randomised double-blind placebo-controlled parallel two-limb study

Double-blind study, with randomisation undertaken by Barts Cardiovascular Clinical Trials Unit

Patients with severe Mitral Regurgitation without evidence of ischemia are tested prior to surgery and after valve repair.

Mitral Regurgitation

University of Alabama at Birmingham

Molecular Mechanisms of Mitral Regurgitation-Aim 2

The Study to Define the Unique Molecular Mechanisms of Mitral Regurgitation in Order to Find New Targeted Therapy to Attenuate the Remodeling and Delay the Need for Surgery and Improve Surgical Outcomes.

xanthine/ניוון ביולוגיה

A Study of Verinurad and Allopurinol in Patients With Chronic Kidney Disease and Hyperuricaemia

Effect of Dietary Nitrate Ingestion in Heart Failure

Molecular Mechanisms of Mitral Regurgitation-Aim 2

המאגר השלם ביותר של צמחי מרפא המגובה על ידי המדע