Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial
Authors: Al-Ajlan Fahad S. , Gladstone David J. , Song Dongbeom , Thorpe Kevin E. , Swartz Rick H. , Butcher Kenneth S. , del Campo Martin , Dowlatshahi Dar , Gensicke Henrik , Lee Gloria Jooyoung , Flaherty Matthew L. , Hill Michael D. , Aviv Richard I. , Demchuk Andrew M. , Swartz Richard H. , Gladstone David J. , Boyle Karl , Braganza Maria , Fedasko Nadia , Golob Dolores , Bardi Edith , Senyshyn Samantha , Cayley Megan , Colavecchia Connie , Demchuk Andrew M. , Hill Michael D. , Coutts Shelagh , Klein Gary , Menon Bijoy , Watson Tim , Smith Eric , Subramaniam Suresh , Bal Simerpreet , Barber Philip , Camden Marie-Christine , Horton Myles , Mishra Sachin , Nambiar Vivek , Torres Andres Venegas , Adatia Sweta , Alseraya Amjad , Desai Jamsheed , Mandzia Jennifer , Shamy Michel , Trivedi Anurag , Choi Philip , Dubuc Veronique , Klourfeld Evgenia , Field Thalia , Singh Dilip , Musuka Tapuwa , Bloujney Sarah , Nikneshan Davar , Imoukhuede Oje , Yu Amy , Appireddy Ramana , Evans Jamie , Ryckborst Karla , Calvert Carly , Dowlatshahi Dariush , Stotts Grant , Sharma Mukul , Robert Sohail , Mortensen Melodie , Shamloul Rany , Campo Martin Del , Silver Frank L. , Casaubon Leanne , Jaigobin Cheryl , Perez Yael , Kalman Libby , Abraham Jemini , Wiegner Relu , Cayley Anne , Riediger Victoria , Butcher Ken , Kate Mahesh , Jeerakathil Thomas , Shuaib Ashfaq , Gaucher Sylvia , Sivakumar Leka , Yip Samuel , Teal Philip , Woolfenden Andrew , Benavente Oscar , Beckman Jeff , Murphy Colleen , Field Thalia , Asdaghi Negar , Villaluna-MurrVay Karina , Sahlas Demetrios J. , Algird Almunder , Knapman Jordan , Macmillan Sue , Sancan Janice , Mehdiratta Manu , Perez Yael , John Verity , Dhanani AlNoor , Temple Bryan , Douen Andre , Selchen Daniel , Saposnik Gustavo , Kostyrko Pawel , Chan Richard , Young Bryan , Kumar Balagopal , Soros Peter , Hesser Kimberley , Wright Mary , Frank Connie , Amato-Marziali Belinda , Deschaintre Yan , Poppe Alexandre , Lapierre Marlene , Boulanger Jean-Martin , Berger Leo , Blais Lise , Simard Christel , Teitelbaum Jeanne , Campbell Natasha , Jin Al , Breen Adriana , Bickford Suzanne 
Published: February 2023

Background:
In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 μg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion.

Methods:
Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration.

Results:

Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2–2.6). Median time from baseline CT to study drug was 62.5 (55–80) minutes, and from study drug to early post-dose CT was 19 (14.5–30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (−0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8–8.3) in the placebo arm (
P
=0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (−2.6 to 8.3) in the rFVIIa arm and 0.7 mL (−1.6 to 2.1) in the placebo arm (
P
=0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71–1.43];
P
=0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994–1.003];
P
=0.50; Table 3).

Conclusions:
In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01359202.