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Rahbar MH, Dickerson AS, Cai C, et al. Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial. Contemp Clin Trials. 2015;44:139-148doi: 10.1016/j.cct.2015.08.007.
Rahbar, M. H., Dickerson, A. S., Cai, C., Pedroza, C., Hessabi, M., Shen, L., Pandurengan, R., Jacobs, A. N. M., Indupuru, H., Sline, M. R., Delgado, R. I., Macdonald, C., Ford, G. A., Grotta, J. C., & Barreto, A. D. (2015). Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial. Contemporary clinical trials, 44139-148. https://doi.org/10.1016/j.cct.2015.08.007
Rahbar, Mohammad H, et al. "Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial." Contemporary clinical trials vol. 44 (2015): 139-148. doi: https://doi.org/10.1016/j.cct.2015.08.007
Rahbar MH, Dickerson AS, Cai C, Pedroza C, Hessabi M, Shen L, Pandurengan R, Jacobs ANM, Indupuru H, Sline MR, Delgado RI, Macdonald C, Ford GA, Grotta JC, Barreto AD. Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial. Contemp Clin Trials. 2015 Sep;44:139-148. doi: 10.1016/j.cct.2015.08.007. Epub 2015 Aug 13. PMID: 26278031.
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Contemp Clin Trials. 2015 Sep;44:139-148. doi: 10.1016/j.cct.2015.08.007. Epub 2015 Aug 13.

Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial.

Contemporary clinical trials

Mohammad H Rahbar, Aisha S Dickerson, Chunyan Cai, Claudia Pedroza, Manouchehr Hessabi, Loren Shen, Renganayaki Pandurengan, Amber Nicole M Jacobs, Hari Indupuru, Melvin R Sline, Rigoberto I Delgado, Claire Macdonald, Gary A Ford, James C Grotta, Andrew D Barreto

Affiliations

  1. Division of Clinical and Translational Sciences, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA; Division of Epidemiology, Human Genetics, and Environmental Sciences (EHGES), University of Texas School of Public Health at Houston, Houston, TX 77030, USA; Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  2. Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  3. Division of Clinical and Translational Sciences, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA; Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  4. Center for Clinical Research and Evidence-Based Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  5. Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  6. Department of Neurology, Stroke Program, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  7. Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  8. Department of Neurology, Stroke Program, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  9. Department of Neurology, Stroke Program, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  10. Department of Neurology, Stroke Program, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  11. Department of Management, Policy & Community Health, University of Texas School of Public Health at Houston, Houston, TX 77030, USA. Electronic address: [email protected].
  12. Newcastle Clinical Trials Unit (NCTU), Newcastle University, Newcastle upon Tyne NE2 4AE, United Kingdom. Electronic address: [email protected].
  13. Newcastle Clinical Trials Unit (NCTU), Newcastle University, Newcastle upon Tyne NE2 4AE, United Kingdom; Oxford Academic Health Science Network, Magdalen Centre North, Oxford Science Park, OX4 4GA, United Kingdom. Electronic address: [email protected].
  14. Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX 77030, USA. Electronic address: [email protected].
  15. Department of Neurology, Stroke Program, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: [email protected].

PMID: 26278031 DOI: 10.1016/j.cct.2015.08.007

Abstract

BACKGROUND: We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2).

METHODS: ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fisher's exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms.

RESULTS: Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3-5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured.

CONCLUSIONS: We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality.

Copyright © 2015. Published by Elsevier Inc.

Keywords: Acute Stroke; Adaptive design; Argatroban; Bayesian methods; Data quality assurance; Multisite randomized clinical trials

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