BACKGROUND: We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of @entity20806 in Combination with Recombinant @entity1456 for @entity64 (ARTSS-2). METHODS: ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of @entity20806 injection (low, high) in combination with recombinant @entity1456 (rt-PA) in acute @entity385 @entity1 and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as @entity548 ( @entity548 ) score and presence of @entity432 ( @entity432 ). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 @entity1 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 @entity20806 arms. RESULTS: Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), @entity548 score (0-2 vs. 3-5, P =1.0), and @entity432 (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose @entity20806 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.

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

@entity1 :: ('9606', 'Species') :: ['patients'] @entity64 :: ('MESH:D020521', 'Disease') :: ['Acute Stroke'] @entity548 :: ('MESH:D006470', 'Disease') :: ['HAT', 'hemorrhage after thrombolysis'] @entity20806 :: ('MESH:C031942', 'Chemical') :: ['Argatroban'] @entity1456 :: ('100128998', 'Gene') :: ['Tissue Plasminogen Activator', 'tissue plasminogen activator'] @entity432 :: ('MESH:D001157', 'Disease') :: ['distal internal carotid artery occlusion', 'DICAO'] @entity385 :: ('MESH:D002544', 'Disease') :: ['ischemic stroke']
@entity64 :: (MESH:D020521,Disease) :: ['Acute Stroke']
