TY - JOUR
T1 - National Institutes of Health Stroke Scale
T2 - An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke
AU - Chalos, Vicky
AU - van der Ende, Nadinda A. M.
AU - Lingsma, Hester F.
AU - Mulder, Maxim J. H. L.
AU - Venema, Esmee
AU - Dijkland, Simone A.
AU - Berkhemer, Olvert A.
AU - Yoo, Albert J.
AU - Broderick, Joseph P.
AU - Palesch, Yuko Y.
AU - Yeatts, Sharon D.
AU - Roos, Yvo B. W. E. M.
AU - van Oostenbrugge, Robert J.
AU - van Zwam, Wim H.
AU - Majoie, Charles B. L. M.
AU - van der Lugt, Aad
AU - Roozenbeek, Bob
AU - Dippel, Diederik W. J.
AU - Berkhemer, Olvert A.
AU - Fransen, Puck S. S.
AU - Beumer, Debbie
AU - van den Berg, Lucie A.
AU - Lingsma, Hester F.
AU - Yoo, Albert J.
AU - Schonewille, Wouter J.
AU - Vos, Jan Albert
AU - Nederkoorn, Paul J.
AU - Wermer, Marieke J. H.
AU - van Walderveen, Marianne A. A.
AU - Staals, Julie
AU - Hofmeijer, Jeannette
AU - van Oostayen, Jacques A.
AU - Nijeholt, Geert J. Lycklama A.
AU - Boiten, Jelis
AU - Brouwer, Patrick A.
AU - Emmer, Bart J.
AU - de Bruijn, Sebastiaan F.
AU - van Dijk, Lukas C.
AU - Kappelle, L. Jaap
AU - Lo, Rob H.
AU - van Dijk, Ewoud J.
AU - de Vries, Joost
AU - de Kort, Paul L. M.
AU - van Rooij, Willem Jan J.
AU - van den Berg, Jan S. P.
AU - van Hasselt, Boudewijn A. A. M.
AU - Aerden, Leo A. M.
AU - Dallinga, Rene J.
AU - Visser, Marieke C.
AU - Bot, Joseph C. J.
AU - MR CLEAN Investigators
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - endovascular treatment
KW - informed consent
KW - NIHSS
KW - outcome
KW - stroke
KW - thrombectomy
KW - SURROGATE END-POINTS
KW - CLINICAL-TRIALS
KW - PLASMINOGEN-ACTIVATOR
KW - ENDOVASCULAR THERAPY
KW - RANDOMIZED-TRIAL
KW - THROMBECTOMY
KW - ALTEPLASE
KW - SEVERITY
U2 - 10.1161/STROKEAHA.119.026791
DO - 10.1161/STROKEAHA.119.026791
M3 - Article
C2 - 31795895
SN - 0039-2499
VL - 51
SP - 282
EP - 290
JO - Stroke
JF - Stroke
IS - 1
ER -