Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke). Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Barreto, Andrew D.; Ford, Gary A.; Shen, Loren; Pedroza, Claudia; Tyson, Jon; Cai, Chunyan; Rahbar, Mohammad H.; Grotta, James C.; Ajani, Zahra; Alexandrov, Andrei V.; Cherches, Igor; Coull, Bruce; Dawson, Jesse; del Junco, Debra; Demchuk, Andrew; Devine, Joseph; Dickerson, Aisha S.; Dixit, Anand; Frey, James L.; James, Martin; Khan, Usman; Levine, Steven; MacDonald, Claire; Malkoff, Marc; McColl, Elaine; Misra, Vivek; Mullen, Michael; Perry, Richard; Piechowski-Jozwiak, Bartlomiej; Roffe, Christine; Sangha, Navi; Sisson, April; Tsivgoulis, Georgios; Volpi, John J.;
• Is Part Of: Stroke. Volume 48:Issue 6(2017)
• Publication Date: 2017-06
• Subjects: acute stroke -- adjunctive therapy -- anticoagulation -- argatroban -- randomized controlled trial -- thrombin inhibitor -- thrombolysis; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.117.016720
• Languages: English
• ISSNs: 0039-2499

Abstract

Abstract : Background and Purpose—: We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to recombinant tissue-type plasminogen activator (r-tPA)–treated ischemic stroke patients. Methods—: Patients treated with standard-dose r-tPA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100 μg/kg bolus) followed by infusion of either 1 (low dose) or 3 μg/kg per minute (high dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage. Probability of clinical benefit (modified Rankin Scale score 0–1 at 90 days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk, 1.0 and 95% prior intervals, 0.33–3.0). Results—: Ninety patients were randomized: 29 to r-tPA alone, 30 to r-tPA+low-dose argatroban, and 31 to r-tPA+high-dose argatroban. Rates of symptomatic intracerebral hemorrhage were similar among control, low-dose, and high-dose arms: 3/29 (10%), 4/30 (13%), and 2/31 (7%), respectively. At 90 days, 6 (21%) r-tPA alone, 9 (30%) low-dose, and 10 (32%) high-dose patients were with modified Rankin Scale score 0 to 1. The relative risks (95% credible interval) for modified Rankin Scale score 0 to 1 with low, high, and either low or high dose argatroban were 1.17 (0.57–2.37), 1.27 (0.63–2.53), and 1.34 (0.68–2.76), respectively. The probability that adjunctive argatroban was superior to r-tPA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively. Conclusions—: In patients treated with r-tPA, adjunctive argatroban was not associated with increased risk of symptomatic intracerebral hemorrhage and provides evidence that a definitive effectiveness trial is indicated. Clinical Trial Registration—: URL:http://www.clinicaltrials.gov . Unique Identifier: NCT01464788. Abstract : Supplemental Digital Content is available in the text.