Monitoring disease progression with plasma creatinine in amyotrophic lateral sclerosis clinical trials
Van Eijk, Ruben P.A.; Eijkemans, Marinus J.C.; Ferguson, Toby A.; Nikolakopoulos, Stavros; Veldink, Jan H.; Van Den Berg, Leonard H.
(2018) Journal of Neurology, Neurosurgery and Psychiatry, volume 89, issue 2, pp. 156 - 161
(Article)
Abstract
OBJECTIVES: Plasma creatinine is a predictor of survival in amyotrophic lateral sclerosis (ALS). It remains, however, to be established whether it can monitor disease progression and serve as surrogate endpoint in clinical trials. METHODS: We used clinical trial data from three cohorts of clinical trial participants in the LITRA, EMPOWER
... read more
and PROACT studies. Longitudinal associations between functional decline, muscle strength and survival with plasma creatinine were assessed. Results were translated to trial design in terms of sample size and power. RESULTS: A total of 13 564 measurements were obtained for 1241 patients. The variability between patients in rate of decline was lower in plasma creatinine than in ALS functional rating scale-Revised (ALSFRS-R; p<0.001). The average rate of decline was faster in the ALSFRS-R, with less between-patient variability at baseline (p<0.001). Plasma creatinine had strong longitudinal correlations with the ALSFRS-R (0.43 (0.39-0.46), p<0.001), muscle strength (0.55 (0.51-0.58), p<0.001) and overall mortality (HR 0.88 (0.86-0.91, p<0.001)). Using plasma creatinine as outcome could reduce the sample size in trials by 21.5% at 18 months. For trials up to 10 months, the ALSFRS-R required a lower sample size. CONCLUSIONS: Plasma creatinine is an inexpensive and easily accessible biomarker that exhibits less variability between patients with ALS over time and is predictive for the patient's functional status, muscle strength and mortality risk. Plasma creatinine may, therefore, increase the power to detect treatment effects and could be incorporated in future ALS clinical trials as potential surrogate outcome.
show less
Download/Full Text
The full text of this publication is not available.
Keywords: amyotrophic lateral sclerosis, clinical trials, disease progression, plasma creatinine, Amyotrophic Lateral Sclerosis/blood, Humans, Middle Aged, Male, Survival Rate, Clinical Trials as Topic, Creatinine/blood, Disease Progression, Female, Aged, Longitudinal Studies, Muscle Strength, Clinical Neurology, Psychiatry and Mental health, Surgery, Journal Article
ISSN: 0022-3050
Publisher: BMJ Publishing Group
Note: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
(Peer reviewed)