Chenchen Wei1,2,3, Jeffrey Wang1, Lydia D Foster4, Sharon D Yeatts4, Claudia Moy5, J Mocco6, Magdy Selim1. 1. Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.W., J.W., M.S.). 2. Department of Neurology, The Affiliated Hospital of Qingdao University, China (C.W.). 3. Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (C.W.). 4. Department of Public Health Sciences, Medical University of South Carolina, Charleston (L.D.F., S.D.Y.). 5. National Institute of Neurological Disorders and Stroke, Bethesda, MD (C.M.). 6. Department of Neurosurgery, Mount Sinai Health System, Icahn School of Medicine, New York (J.M.).
Abstract
BACKGROUND: Hematoma volume (HV) is a powerful determinant of outcome after intracerebral hemorrhage. We examined whether the effect of the iron chelator, deferoxamine, on functional outcome varied depending on HV in the i-DEF trial (Intracerebral Hemorrhage Deferoxamine). METHODS: A post hoc analysis of the i-DEF trial; participants were classified according to baseline HV (small <10 mL, moderate 10-30 mL, and large >30 mL). Favorable outcome was defined as a modified Rankin Scale score of 0-2 at day-180; secondarily at day-90. Logistic regression was used to evaluate the differential treatment effect according to HV. RESULTS: Two hundred ninety-one subjects were included in the as-treated analysis; 121 with small, 114 moderate, and 56 large HV. Day-180 modified Rankin Scale scores were available for 270/291 subjects (111 with small, 105 moderate, and 54 large HV). There was a differential effect of treatment according to HV on day-180 outcomes (P-for-interaction =0.0077); 50% (27/54) of deferoxamine-treated patients with moderate HV had favorable outcome compared with 25.5% (13/51) of placebo-treated subjects (adjusted odds ratio, 2.7 [95% CI, 1.13-6.27]; P=0.0258). Treatment effect was not significant for small (adjusted odds ratio, 1.37 [95% CI, 0.62-3.02]) or large (adjusted odds ratio, 0.12 [95% CI, 0.01-1.05]) HV. Results for day-90 outcomes were comparable (P-for-interaction =0.0617). Sensitivity analyses yielded similar results. CONCLUSIONS: Among patients with moderate HV, a greater proportion of deferoxamine- than placebo-treated patients achieved modified Rankin Scale score 0-2. The treatment effect was not significant for small or large HVs. These findings have important trial design and therapeutic implications. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02175225.
BACKGROUND: Hematoma volume (HV) is a powerful determinant of outcome after intracerebral hemorrhage. We examined whether the effect of the iron chelator, deferoxamine, on functional outcome varied depending on HV in the i-DEF trial (Intracerebral Hemorrhage Deferoxamine). METHODS: A post hoc analysis of the i-DEF trial; participants were classified according to baseline HV (small <10 mL, moderate 10-30 mL, and large >30 mL). Favorable outcome was defined as a modified Rankin Scale score of 0-2 at day-180; secondarily at day-90. Logistic regression was used to evaluate the differential treatment effect according to HV. RESULTS: Two hundred ninety-one subjects were included in the as-treated analysis; 121 with small, 114 moderate, and 56 large HV. Day-180 modified Rankin Scale scores were available for 270/291 subjects (111 with small, 105 moderate, and 54 large HV). There was a differential effect of treatment according to HV on day-180 outcomes (P-for-interaction =0.0077); 50% (27/54) of deferoxamine-treated patients with moderate HV had favorable outcome compared with 25.5% (13/51) of placebo-treated subjects (adjusted odds ratio, 2.7 [95% CI, 1.13-6.27]; P=0.0258). Treatment effect was not significant for small (adjusted odds ratio, 1.37 [95% CI, 0.62-3.02]) or large (adjusted odds ratio, 0.12 [95% CI, 0.01-1.05]) HV. Results for day-90 outcomes were comparable (P-for-interaction =0.0617). Sensitivity analyses yielded similar results. CONCLUSIONS: Among patients with moderate HV, a greater proportion of deferoxamine- than placebo-treated patients achieved modified Rankin Scale score 0-2. The treatment effect was not significant for small or large HVs. These findings have important trial design and therapeutic implications. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02175225.
Entities:
Keywords:
deferoxamine; hematoma; hemorrhage; iron; odds ratio
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