title: The ThRombolysis in UnconTrolled Hypertension (TRUTH) protocol: an observational study on treatment strategy of elevated blood pressure in stroke patients eligible for IVT.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands. t.p.zonneveld@amc.uva.nl.
authors.forename: T P
authors.initials: TP
authors.lastname: Zonneveld
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. a.algra@umcutrecht.nl.|The Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands. a.algra@umcutrecht.nl.
authors.forename: A
authors.initials: A
authors.lastname: Algra
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. d.dippel@erasmusmc.nl.
authors.forename: D W J
authors.initials: DW
authors.lastname: Dippel
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. l.kappelle@umcutrecht.nl.
authors.forename: L J
authors.initials: LJ
authors.lastname: Kappelle
authors.affiliation: Department of Neurology, Maastricht UMC+, Maastricht, The Netherlands. r.van.oostenbrugge@mumc.nl.
authors.forename: R J
authors.initials: RJ
authors.lastname: van Oostenbrugge
authors.affiliation: Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands. y.b.roos@amc.uva.nl.
authors.forename: Y B W E M
authors.initials: YB
authors.lastname: Roos
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. m.j.h.wermer@lumc.nl.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wermer
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. h.b.vanderworp@umcutrecht.nl.
authors.forename: H B
authors.initials: HB
authors.lastname: van der Worp
authors.affiliation: Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands. p.j.nederkoorn@amc.uva.nl.
authors.forename: P J
authors.initials: PJ
authors.lastname: Nederkoorn
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. ndkruyt@gmail.com.
authors.forename: N D
authors.initials: ND
authors.lastname: Kruyt
mesh_terms: D061605:Administration, Intravenous; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator