Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial.
BACKGROUND
There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial.


METHODS
Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096.


RESULTS
Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days.


CONCLUSIONS
Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH.


BACKGROUND
National Health and Medical Research Council of Australia.
Anderson
Craig S
CS
The George Institute for International Health, The University of Sydney and Royal Prince Alfred Hospital, Sydney, Australia. canderson@george.org.au
Huang
Yining
Y
Wang
Ji Guang
JG
Arima
Hisatomi
H
Neal
Bruce
B
Peng
Bin
B
Heeley
Emma
E
Skulina
Christian
C
Parsons
Mark W
MW
Kim
Jong Sung
JS
Tao
Qing Ling
QL
Li
Yue Chun
YC
Jiang
Jian Dong
JD
Tai
Li Wen
LW
Zhang
Jin Li
JL
Xu
En
E
Cheng
Yan
Y
Heritier
Stephane
S
Morgenstern
Lewis B
LB
Chalmers
John
J
D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology*; D003422:Critical Care / Q000379:methods*; D004232:Diuretics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D040242:Risk Reduction Behavior; D016037:Single-Blind Method; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics