Zonneveld T P, Algra A, Dippel D W J, Kappelle L J, van Oostenbrugge R J, Roos Y B W E M, Wermer M J, van der Worp H B, Nederkoorn P J, Kruyt N D
Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
BMC Neurol. 2015 Nov 23;15:241. doi: 10.1186/s12883-015-0493-z.
Intravenous thrombolysis (IVT) with (recombinant) tissue plasminogen activator is an effective treatment in acute ischemic stroke. However, IVT is contraindicated when blood pressure is above 185/110 mmHg, because of an increased risk on symptomatic intracranial hemorrhage. In current Dutch clinical practice, two distinct strategies are used in this situation. The active strategy comprises lowering blood pressure with antihypertensive agents below these thresholds to allow start of IVT. In the conservative strategy, IVT is administered only when blood pressure drops spontaneously below protocolled thresholds. A retrospective analysis in two recent stroke trials showed a non-significant signal towards better functional outcome in the active group; robust evidence for either strategy, however, is lacking. We hypothesize that (I) the active strategy leads to a better functional outcome three months after acute ischemic stroke. Secondary hypotheses are that this effect occurs despite (II) increasing the number of symptomatic intracranial hemorrhages, and could be attributable to (III) a higher rate of IVT treatments and (IV) a shorter door-to-needle time.
The TRUTH is a prospective, observational, cluster-based, parallel group follow-up study; in which participating centers continue their current local treatment guidelines. Outcomes of patients admitted to centers with an active will be compared to those admitted to centers with a conservative strategy. The primary outcome is functional outcome on the modified Rankin Scale at three months. Secondary outcomes are symptomatic intracranial hemorrhage, IVT treatment and door-to-needle time. We based our sample size estimate on an ordinal analysis of the mRS with the "proportional odds" model. With the aforementioned signal observed in a recent retrospective study in these patients as an estimate of the effect size and with alpha 0 · 05, this analysis would have an 80 % power with a total number of 600 patients. Corrections for expected imbalance in group size and clustering effects resulted in a sample size of 1235 patients.
The TRUTH is the first large prospective study specifically studying IVT-candidates with elevated blood pressure, and has the potential to change clinical practice and optimize acute stroke care in these patients.
使用（重组）组织纤溶酶原激活剂进行静脉溶栓是急性缺血性卒中的一种有效治疗方法。然而，当血压高于185/110 mmHg时，静脉溶栓是禁忌的，因为有症状性颅内出血的风险增加。在荷兰目前的临床实践中，在这种情况下使用两种不同的策略。积极策略包括使用抗高血压药物将血压降至这些阈值以下，以便开始静脉溶栓。在保守策略中，仅当血压自发降至预定阈值以下时才进行静脉溶栓。最近两项卒中试验的回顾性分析显示，积极治疗组在功能结局方面有一个不显著的改善信号；然而，对于这两种策略都缺乏有力的证据。我们假设：（I）积极策略会使急性缺血性卒中三个月后的功能结局更好。次要假设是，尽管（II）有症状性颅内出血的数量增加，但这种效果仍然会出现，并且可能归因于（III）更高的静脉溶栓治疗率和（IV）更短的门到针时间。
TRUTH研究是一项前瞻性、观察性、基于群组的平行组随访研究；参与研究的中心继续遵循其当前的当地治疗指南。将积极治疗策略中心收治的患者结局与保守策略中心收治的患者结局进行比较。主要结局是三个月时改良Rankin量表的功能结局。次要结局是症状性颅内出血、静脉溶栓治疗和门到针时间。我们基于使用“比例优势”模型对改良Rankin量表进行的有序分析来估计样本量。以最近对这些患者的回顾性研究中观察到的上述信号作为效应大小的估计值，且α = 0.05，该分析在总共600名患者时将具有80%的检验效能。对预期的组间大小不平衡和聚类效应进行校正后，样本量为1235名患者。
TRUTH研究是第一项专门针对血压升高的静脉溶栓候选患者的大型前瞻性研究，有可能改变临床实践并优化这些患者的急性卒中治疗。
