Abstract | BACKGROUND: PURPOSE: METHODS: Subjects with mild-moderate chronic kidney disease are randomized to paricalcitol or placebo after confirming left ventricular hypertrophy using a cardiac echocardiogram. Cardiac magnetic resonance imaging is then used to assess left ventricular mass index at baseline, 24 and 48 weeks, which is the primary efficacy endpoint of the study. Because of limited prior data to estimate sample size, a maximum information group sequential design with sample size re-estimation is implemented to allow sample size adjustment based on the nuisance parameter estimated using the interim data. An interim efficacy analysis is planned at a pre-specified time point conditioned on the status of enrollment. The decision to increase sample size depends on the observed treatment effect. A repeated measures analysis model, using available data at Week 24 and 48 with a backup model of an ANCOVA analyzing change from baseline to the final nonmissing observation, are pre-specified to evaluate the treatment effect. Gamma-family of spending function is employed to control family-wise Type I error rate as stopping for success is planned in the interim efficacy analysis. LIMITATIONS: If enrollment is slower than anticipated, the smaller sample size used in the interim efficacy analysis and the greater percent of missing week 48 data might decrease the parameter estimation accuracy, either for the nuisance parameter or for the treatment effect, which might in turn affect the interim decision-making. CONCLUSIONS: The application of combining a group sequential design with a sample-size re-estimation in clinical trial design has the potential to improve efficiency and to increase the probability of trial success while ensuring integrity of the study.
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Authors | Yili Pritchett, Yannis Jemiai, Yuchiao Chang, Ishir Bhan, Rajiv Agarwal, Carmine Zoccali, Christoph Wanner, Donald Lloyd-Jones, Jorge B Cannata-Andía, Taylor Thompson, Evan Appelbaum, Paul Audhya, Dennis Andress, Wuyan Zhang, Scott Solomon, Warren J Manning, Ravi Thadhani |
Journal | Clinical trials (London, England)
(Clin Trials)
Vol. 8
Issue 2
Pg. 165-74
(Apr 2011)
ISSN: 1740-7753 [Electronic] England |
PMID | 21478328
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bone Density Conservation Agents
- Ergocalciferols
- Receptors, Calcitriol
- paricalcitol
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Topics |
- Bone Density Conservation Agents
(therapeutic use)
- Data Interpretation, Statistical
- Ergocalciferols
(therapeutic use)
- Female
- Humans
- Hypertrophy, Left Ventricular
(drug therapy)
- Kidney Failure, Chronic
(complications)
- Male
- Receptors, Calcitriol
(agonists)
- Sample Size
- Time Factors
- Treatment Outcome
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