Dataset Information

Number and frequency of albuminuria measurements in clinical trials in diabetic nephropathy.

ABSTRACT:

Background and objectives

Albuminuria change is often used to assess drug efficacy in intervention trials in nephrology. The change is often calculated using a variable number of urine samples collected at baseline and end of treatment. Yet more albuminuria measurements usually occur. Because albuminuria shows a large day-to-day variability, this study assessed to what extent the average and the precision of the antialbuminuric drug effect varies with the number of urine collections at each visit and the number of follow-up visits.

Design, setting, participants, & measurements

This study used data from three randomized intervention trials (Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist Atrasentan) including patients with type 2 diabetes and macroalbuminuria. Albuminuria-lowering drug effects were estimated from one, two, or three urine collections at consecutive days before each study visit and reported as albuminuria change from baseline to end of treatment or the change over time considering an average of all follow-up albuminuria measurements.

Results

Increasing the number of urine collections for an albuminuria measurement at baseline and end of treatment or using all study visits during follow-up did not alter the average drug effect. The precision of the drug effect increased (decreased SEM) when the number of study visits and the number of urine collections per visit were increased. Using all albuminuria measurements at all study visits led to a 4- to 6-fold reduction in sample size to detect a 30% albuminuria-lowering treatment effect with 80% power compared with using baseline and end-of-treatment albuminuria measurements alone.

Conclusions

Increasing the number of urine collections per study visit and the number of visits over time does not change the average drug effect estimate but markedly increases the precision, thereby enhancing statistical power. Thus, clinical trial designs in diabetic nephropathy using albuminuria as an end point can be significantly improved, leading to smaller sample sizes and less complex trials.

SUBMITTER: Kropelin TF

PROVIDER: S-EPMC4348688 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Publications

Number and frequency of albuminuria measurements in clinical trials in diabetic nephropathy.

Kröpelin Tobias F TF de Zeeuw Dick D Andress Dennis L DL Bijlsma Maarten J MJ Persson Frederik F Parving Hans-Henrik HH Heerspink Hiddo J Lambers HJ

Clinical journal of the American Society of Nephrology : CJASN 20150107 3

<h4>Background and objectives</h4>Albuminuria change is often used to assess drug efficacy in intervention trials in nephrology. The change is often calculated using a variable number of urine samples collected at baseline and end of treatment. Yet more albuminuria measurements usually occur. Because albuminuria shows a large day-to-day variability, this study assessed to what extent the average and the precision of the antialbuminuric drug effect varies with the number of urine collections at e ...[more]

PMID: 25568217

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Project description:IntroductionTreatment options and decisions are often based on the results of clinical trials. We have evaluated the public availability of results from completed, registered phase III clinical trials on diabetic nephropathy and current treatment options.MethodsThis was a cross-sectional analysis in which STrengthening the Reporting of OBservational studies in Epidemiology criteria were applied for design and analysis. In June 2017, 34 completed phase III clinical trials on diabetic nephropathy in the ClinicalTrials. gov registry were identified and matched to publications in the ClinicalTrials.gov registry and to those in the PubMed and Google Scholar databases. If no publication was identified, the principal investigator was contacted. The ratio of published and non-published studies was calculated. Various parameters, including study design, drugs, and comparators provided, were analyzed.ResultsDrugs/supplements belonged to 26 different categories of medications, with the main ones being angiotensin-converting enzyme inhibitors, angiotensin-II receptors blockers, and dipeptidyl-peptidase-4-inhibitors. Among the trials completed before 2016 (n = 32), 22 (69%) were published, and ten (31%) remained unpublished. Thus, data on 11 different interventions and more than 1000 patients remained undisclosed. Mean time to publication was 26.5 months, which is longer than the time constrictions imposed by the U.S. Food and Drug Administration Amendments Act. Most trials only showed weak effects on micro- and macroalbuminuria, with an absolute risk reduction of 1.0 and 0.3%, respectively, and the number needed to treat varied between 91 and 333, without any relevant effect on end-stage-renal disease by intensive glucose-lowering treatment. Comparison of the results, however, was difficult since study design, interventions, and the renal outcome parameters vary greatly between the studies.ConclusionDespite the financial and human resources involved and the relevance for therapeutic guidelines and clinical decisions, about one-third of phase III clinical trials on diabetic nephropathy remain unpublished. Interventions used in published trials showed a low efficacy on renal outcome.FundingDeutsche Forschungsgemeinschaft (DFG): SFB 1118.

Dataset Information

Number and frequency of albuminuria measurements in clinical trials in diabetic nephropathy.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

Number and frequency of albuminuria measurements in clinical trials in diabetic nephropathy.

Similar Datasets

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