Elsevier

The Lancet Neurology

Volume 7, Issue 5, May 2008, Pages 391-399
The Lancet Neurology

Fast track — Articles
Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial

https://doi.org/10.1016/S1474-4422(08)70069-3Get rights and content

Summary

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.

Findings

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 ≥33% 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.

Interpretation

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.

Funding

National Health and Medical Research Council of Australia.

Introduction

Intracerebral haemorrhage (ICH) is estimated to affect over 1 million people worldwide each year,1, 2 most of whom either die or are left seriously disabled.1, 2, 3 Early elevation of blood pressure is very common after ICH and is associated with poor outcome,4, 5, 6, 7, 8, 9, 10 and several non-randomised studies11, 12, 13 suggest that early lowering of blood pressure is beneficial in hypertensive patients with ICH. Clinical guidelines for the early management of blood pressure in ICH highlight the need for a definitive study, because recommendations are based primarily on expert opinion with no evidence from randomised trials to define either when treatment should be initiated or the extent to which blood pressure should be lowered.14, 15, 16 We report the results of the first phase of the intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT). This phase was done to establish the feasibility of early intensive lowering of blood pressure in ICH and to define effects on haematoma growth and key safety parameters. We intended to follow this run-in phase with the main phase of INTERACT, with several thousand patients; however, the executive committee decided in February, 2007, to close the run-in study after follow-up of the required number of patients, which was completed in August, 2007, because recruitment of patients was more rapid than expected and the required number was enrolled before funding was secured for the main phase.

Section snippets

Participants

This investigator-initiated, multicentre, open, blinded outcome, randomised trial enrolled patients from 44 hospital sites in Australia, China, and South Korea. Eligible patients were at least 18 years of age, had spontaneous ICH confirmed by CT and elevated systolic blood pressure (≥2 measurements of 150–220 mm Hg, recorded ≥2 min apart), and were able to commence the randomly assigned treatment within 6 h of ICH onset in a suitably monitored environment. Patients were excluded for the

Results

Between November, 2005, and April, 2007, 2415 patients with suspected ICH were screened and 17% were randomly assigned to receive early intensive treatment or guideline-based treatment to lower blood pressure (figure 1). Baseline demographic and clinical characteristics and the median time from ICH onset to randomisation (about 3·5 h) were similar in the treatment groups (table 1). The proportion of patients who received any treatment to lower blood pressure in the first 24 h after ICH onset

Discussion

In this trial of patients who presented early after the onset of ICH, a management strategy of rapid lowering of blood pressure was applied in routine clinical practice with reasonable efficiency and with careful safety monitoring of patients. Additionally, this treatment seems to attenuate the growth of ICH when compared with a more conservative policy of blood pressure management that was based on a widely used guideline. Because haematoma growth is a strong predictor of morbidity and

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