Department of Public Health Sciences, Medical University of South Carolina, Charleston (L.F., S.D.Y.).
Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (L.R., A.S., V.L., M.S.).
Stroke. 2022 Jul;53(7):2204-2210. doi: 10.1161/STROKEAHA.121.037298. Epub 2022 Mar 21.
There are limited data on the trajectory of recovery and long-term functional outcomes after intracerebral hemorrhage (ICH). Most ICH trials have conventionally assessed outcomes at 3 months following the footsteps of ischemic stroke. The i-DEF trial (Intracerebral Hemorrhage Deferoxamine Trial) assessed modified Rankin Scale (mRS) longitudinally at prespecified time points from day 7 through the end of the 6-month follow-up period. We evaluated the trajectory of mRS among trial participants and examined the effect of deferoxamine on this trajectory.
We performed a post hoc analysis of the i-DEF trial, a multicenter, randomized, placebo-controlled, double-blind, futility-design, phase 2 clinical trial, based on the actual treatment received. Favorable outcome was defined as mRS score of 0-2. A generalized linear mixed model was used to evaluate the outcome trajectory over time, as well as whether the trajectory was altered by deferoxamine, after adjustments for randomization variables, presence of intraventricular hemorrhage, and ICH location.
A total of 291 subjects were included in analysis (145 placebo and 146 deferoxamine). The proportion of patients with mRS score of 0-2 continually increased from day 7 to 180 in both groups (interaction <0.0001 for time in main effects model), but treatment with deferoxamine favorably altered the trajectory (interaction =0.0010). Between day 90 and 180, the deferoxamine group improved (=0.0001), whereas there was not significant improvement in the placebo arm (=0.3005).
A large proportion of patients continue to improve up to 6 months after ICH. Future ICH trials should assess outcomes past 90 days for a minimum of 6 months. In i-DEF, treatment with deferoxamine seemed to accelerate and alter the trajectory of recovery as assessed by mRS.
URL: https://www.
gov; Unique identifier: NCT02175225.
关于脑出血（ICH）后恢复轨迹和长期功能结局的数据有限。大多数 ICH 试验通常都遵循缺血性卒中的脚步，在ICH 后 3 个月评估结果。i-DEF 试验（脑出血去铁胺试验）在预先指定的时间点从第 7 天到 6 个月随访期结束，纵向评估改良 Rankin 量表（mRS）。我们评估了试验参与者的 mRS 轨迹，并检查了去铁胺对该轨迹的影响。
我们对 i-DEF 试验进行了事后分析，该试验是一项多中心、随机、安慰剂对照、双盲、无效性设计、2 期临床试验，基于实际接受的治疗。良好的结局定义为 mRS 评分 0-2。使用广义线性混合模型评估随时间的结局轨迹，以及去铁胺是否在调整随机化变量、存在脑室出血和 ICH 位置后改变轨迹。
共有 291 名受试者纳入分析（145 名安慰剂和 146 名去铁胺）。两组患者 mRS 评分 0-2 的比例从第 7 天持续增加到 180 天（主效应模型中时间的交互<0.0001），但去铁胺治疗显著改变了轨迹（交互=0.0010）。在第 90 天至 180 天之间，去铁胺组改善（=0.0001），而安慰剂组无明显改善（=0.3005）。
很大一部分患者在脑出血后 6 个月内仍继续改善。未来的 ICH 试验应评估至少 6 个月的 90 天后的结局。在 i-DEF 中，去铁胺治疗似乎加速并改变了 mRS 评估的恢复轨迹。
NCT02175225。
