Intensive serum urate lowering with oral urate‐lowering therapy for erosive gout: A randomized double‐blind controlled trial

Objective.Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate (sUA) levels in gouty patients who were either overproducers or underexcretors.Methods.Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2, 28-day, multicenter, randomized, double-blind, placebo-controlled trial and randomized to receive febuxostat 40 mg, 80 mg, or 120 mg daily, or placebo. The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28. Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid (uUA) from baseline to Day 28.Results.Of the 153 subjects, 118 (77%) were underexcretors (uUA ≤ 800 mg/24 h) and 32 (21%) were overproducers (uUA > 800 mg/24 h); baseline uUA data were missing for 3 subjects. Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28. Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group, for both underexcretors and overproducers.Conclusion.Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status.

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Lipid Lowering Therapy with Combination of Niacin and Statin in Women: Age-Related Endothelial Effects

ISRN Vascular Medicine ◽

10.1155/2013/168504 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7

Author(s):

Beth Parker ◽

Kamlesh Kothawade ◽

Namee Kim ◽

Maura Paul-Labrador ◽

Noel Bairey Merz ◽

...

Keyword(s):

Endothelial Function ◽

Vascular Function ◽

Controlled Trial ◽

Pearson Correlation ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Cardiac Events ◽

Double Blind ◽

Lowering Therapy ◽

Age Related

Background. Many women remain at risk for cardiac events despite treatment to reduce low-density lipoprotein cholesterol (LDL-C). We hypothesized that for postmenopausal women treated with niacin in addition to statin vascular function will improve. Methods. We conducted a randomized, double-blind, placebo-controlled trial of 16 weeks of niacin (N) versus placebo (PL) in 43 women (mean age, 67±9 years) previously on statin therapy. Study outcomes included lipoprotein levels, vascular inflammation assessed by high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and endothelial function, assessed as brachial artery flow mediated dilation (FMD). Results. The N group significantly increased HDL-C and decreased LDL-C cholesterol relative to PL (both P<0.01). FMD improved in both groups (P=0.02) irrespective of niacin (P=0.21). Age influenced change in FMD (P=0.01) such that improved FMD (before to after) with lipid lowering therapy was greater with older age (P=0.03 Pearson correlation = 0.34), independent of treatment group. Conclusions. Lipid lowering therapy with combination of niacin and statin does not improve inflammation or endothelial function compared to statin alone. However, older women demonstrate relatively greater endothelial benefit of lipid lowering therapy over 4 months. This trial is registered with Clinicaltrials.gov NCT00590629.

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A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease

ACC Current Journal Review ◽

10.1016/s1062-1458(01)00465-2 ◽

2001 ◽

Vol 10 (6) ◽

pp. 31-32

Author(s):

J Thambyrajah ◽

M.J Landray ◽

H.J Jones ◽

F.J McGlynn ◽

D.C Wheeler ◽

...

Keyword(s):

Coronary Artery Disease ◽

Folic Acid ◽

Coronary Artery ◽

Endothelial Function ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Lowering Therapy ◽

Artery Disease

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A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(01)01235-9 ◽

2001 ◽

Vol 37 (7) ◽

pp. 1858-1863 ◽

Cited By ~ 46

Author(s):

Jeetendra Thambyrajah ◽

Martin J Landray ◽

Heather J Jones ◽

Fiona J McGlynn ◽

David C Wheeler ◽

...

Keyword(s):

Coronary Artery Disease ◽

Folic Acid ◽

Coronary Artery ◽

Endothelial Function ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Lowering Therapy ◽

Artery Disease

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Variation in Serum Urate Levels in the Absence of Gout and Urate Lowering Therapy: An Analysis Using Data from a Randomized Controlled Trial

10.21203/rs.3.rs-115418/v1 ◽

2020 ◽

Author(s):

Andrew Shaffer ◽

Elizabeth Rahn ◽

Kenneth Saag ◽

Amy Mudano ◽

Angelo Gaffo

Keyword(s):

Coefficient Of Variation ◽

Controlled Trial ◽

Study Participant ◽

Serum Urate ◽

Control Group ◽

Lowering Therapy ◽

Significant Difference ◽

Data Points ◽

Single Data ◽

Using Data

Abstract Background: Previous studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA.Methods: Data was analyzed from a cross-over clinical trial of urate-lowering therapy in young adults without a gout diagnosis. In the control phase, sUA levels used for this analysis were collected at 2-4 week intervals. Mean coefficient of variation for sUA was determined, as were rates of conversion between normouricemia (sUA ≤6.8 mg/dL) and hyperuricemia (sUA >6.8 mg/dL). Results: Mean study participant (n = 85) age was 27.8 ± 7.0 years, with 39% female participants and 41% African-American participants. Mean sUA coefficient of variation was 8.5% ± 4.9% (1% to 23%). There was no significant difference in variation between men and women, or between participants initially normouricemic and those who were initially hyperuricemic.Among those initially normouricemic (n=72), 15% converted to hyperuricemia during at least one subsequent measurement. The subgroup with initial sUA <6.0 (n=54) was much less likely to have future values in the range of hyperuricemia compared to the group with screening sUA values between 6.0-6.8 (n=18) (7% vs 39%, p = 0.0037).Of the participants initially hyperuricemic (n=13), 46% were later normouricemic during at least one measurement.Conclusion: Single sUA measurements were unreliable in hyperuricemia classification due to spontaneous variation. Those with an sUA of <6.0 mg/dL were less likely to demonstrate future hyperuricemic measurements and this could be considered a safer threshold to rule out intermittent hyperuricemia based on a single measurement point.Trial registration: Data from parent study ClinicalTrials.gov Identifier: NCT02038179

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Rilonacept (Interleukin-1 Trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: Results of a phase II randomized, double-blind, placebo-controlled trial

Arthritis & Rheumatism ◽

10.1002/art.33412 ◽

2012 ◽

Vol 64 (3) ◽

pp. 876-884 ◽

Cited By ~ 70

Author(s):

H. Ralph Schumacher ◽

John S. Sundy ◽

Robert Terkeltaub ◽

Howard R. Knapp ◽

Scott J. Mellis ◽

...

Keyword(s):

Phase Ii ◽

Controlled Trial ◽

Interleukin 1 ◽

Acute Gout ◽

Double Blind ◽

Double Blind Placebo ◽

Lowering Therapy ◽

Gout Flares

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Effect of tart cherry juice on risk of gout attacks: protocol for a randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2019-035108 ◽

2020 ◽

Vol 10 (3) ◽

pp. e035108

Author(s):

Kirstie Louise Lamb ◽

Anthony Lynn ◽

Jean Russell ◽

Margo E Barker

Keyword(s):

Research Ethics ◽

Outcome Measures ◽

Controlled Trial ◽

Intervention Group ◽

Serum Urate ◽

Secondary Outcome ◽

Primary Study ◽

Tart Cherry ◽

Double Blind ◽

Cherry Juice

IntroductionGout is a painful form of inflammatory arthritis associated with several comorbidities, particularly cardiovascular disease. Cherries, which are rich in anti-inflammatory and antioxidative bioactive compounds, are proposed to be efficacious in preventing and treating gout, but recommendations to patients are conflicting. Cherry consumption has been demonstrated to lower serum urate levels and inflammation in several small studies. One observational case cross-over study reported that cherry consumption was associated with reduced risk of recurrent gout attacks. This preliminary evidence requires substantiation. The proposed randomised clinical trial aims to test the effect of consumption of tart cherry juice on risk of gout attacks.Methods and analysisThis 12-month, parallel, double-blind, randomised, placebo-controlled trial will recruit 120 individuals (aged 18–80 years) with a clinical diagnosis of gout who have self-reported a gout flare in the previous year. Participants will be randomly assigned to an intervention group, which will receive Montmorency tart cherry juice daily for a 12-month period, or a corresponding placebo group, which will receive a cherry-flavoured placebo drink. The primary study outcome is change in frequency of self-reported gout attacks. Secondary outcome measures include attack intensity, serum urate concentration, fractional excretion of uric acid, biomarkers of inflammation, blood lipids and other markers of cardiovascular risk. Other secondary outcome measures will be changes in physical activity and functional status. Statistical analysis will be conducted on an intention-to-treat basis.Ethics and disseminationThis study has been granted ethical approval by the National Research Ethics Service, Yorkshire and The Humber—Leeds West Research Ethics Committee (ref: 18/SW/0262). Results of the trial will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03621215.

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