National Institutes of Health Stroke Scale: An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke

Vicky Chalos*, Nadinda A. M. van der Ende, Hester F. Lingsma, Maxim J. H. L. Mulder, Esmee Venema, Simone A. Dijkland, Olvert A. Berkhemer, Albert J. Yoo, Joseph P. Broderick, Yuko Y. Palesch, Sharon D. Yeatts, Yvo B. W. E. M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Charles B. L. M. Majoie, Aad van der Lugt, Bob Roozenbeek, Diederik W. J. Dippel, Olvert A. Berkhemer, Puck S. S. FransenDebbie Beumer, Lucie A. van den Berg, Hester F. Lingsma, Albert J. Yoo, Wouter J. Schonewille, Jan Albert Vos, Paul J. Nederkoorn, Marieke J. H. Wermer, Marianne A. A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama A. Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, L. Jaap Kappelle, Rob H. Lo, Ewoud J. van Dijk, Joost de Vries, Paul L. M. de Kort, Willem Jan J. van Rooij, Jan S. P. van den Berg, Boudewijn A. A. M. van Hasselt, Leo A. M. Aerden, Rene J. Dallinga, Marieke C. Visser, Joseph C. J. Bot, MR CLEAN Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

38 Citations (Web of Science)

Abstract

Background and Purpose- The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods- We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results- In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22-2.32) to respectively 1.36 (95% CI, 0.97-1.91) and 1.24 (95% CI, 0.87-1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions- The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties.

Original languageEnglish
Pages (from-to)282-290
Number of pages9
JournalStroke
Volume51
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • endovascular treatment
  • informed consent
  • NIHSS
  • outcome
  • stroke
  • thrombectomy
  • SURROGATE END-POINTS
  • CLINICAL-TRIALS
  • PLASMINOGEN-ACTIVATOR
  • ENDOVASCULAR THERAPY
  • RANDOMIZED-TRIAL
  • THROMBECTOMY
  • ALTEPLASE
  • SEVERITY

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