CHHIPS
Controlling Hypertension and Hypotension Immediately Post-Stroke Trial
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Status:
Completed. Trial closed late in 2006 with 180 patients enrolled. Results will be available soon.
Purpose:
To determine the extent to which blood pressure should be managed in the acute stroke setting.
Interventions:
Antihypertensives
This category includes all BP lowering drugs in stroke prevention trials
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Year Started:
2004
Year Finished:
2006
Year Presented:
2008
Design:
Prospective, multi-centre, randomized, double-blind, placebo-controlled, titrated-dose trial.
Inclusion Criteria
Three groups will be studied:
(1) Hypotensive (SBP 140mmHg) non-hemorrhagic, neuroradiologically-confirmed stroke patients treated within 12 hrs of stroke onset
(2) Hypertensive (SBP 160mmHg), non-dysphagic ischemic and hemorrhagic stroke patients within 36 hrs of stroke onset
(3) Hypertensive, dysphagic ischemic and hemorrhagic stroke patients within 36 hrs of stroke onset.
Exclusion Criteria
Patients undergoing thrombolysis; hypertensive encephalopathy; co-existing cardiac or vascular emergency; PICH and SBP>200 mmHg &/or DBP >120 mmHg; impaired conscious level; contra-indications to therapy; pre-morbid dependence; non-stroke diagnosis.
Patient Involvement:
All routine aspects of management of patients will be continued as standard local practice. The following specific interventions will be given to individual groups: (1) intravenous (iv) phenylephrine at 80μg/min or matching placebo (PLA), titrated to target SBP 150mmHg (range 145 to 155) or 15mmHg increase above baseline, and continued until maximum period 24 hrs after stroke onset; (2) oral lisinopril (LIS) 5mg or LAB 50mg or matching PLA, repeated if necessary at 4 and 8 hrs after initial dosing to target SBP 150mmHg (145 to 155) or 15mmHg reduction from baseline, and continued at dose of LIS 5 to 15mg daily or LAB 50 to 150mg twice daily or matching PLA until 2 wks after stroke onset; (3) sublingual (sl) LIS 5mg and iv PLA or sl PLA and iv LAB 50mg or sl and iv PLA, adjusted if necessary at 4 and 8 hours after initial dosing to target SBP 150mmHg (145 to 155) or 15mmHg reduction from baseline, and continued at dose of LIS 5 to 15 mg daily or LAB 50 to 150 mg twice daily or PLA until 72 to 96 hours after stroke onset, thereafter as LIS, LAB or PLA suspension by nasogastric tube (in patients remaining non-dysphagic) or orally (in patients regaining swallow) until 2 weeks after stroke onset.
Primary Outcome:
Primary outcome will be proportion of patients dead or dependent (mRS >3) at 14 days following stroke onset.
Secondary Outcome:
Secondary outcomes will include early (<72 hours) neurological deterioration, stroke recurrence over 2 weeks, treatment discontinuations, trial withdrawals, BP changes at 24 hrs and 2 wks, and health-related quality of life at 3 months.
Results:
Greater BP reductions were seen from 4 to 24 hours following administration with lisinopril (oral or sublingual) or labetalol (oral or intravenous) in dysphagic and non-dysphagic acute stroke patients compared to placebo. SBP, but not DBP, differences between active treatment and placebo were maintained up to two weeks. Discontinuation of medication were similar in active and placebo groups, though greater in dysphagic and non-dysphagic subjects. No increase in adverse side effects was seen with active treatment. BP reduction was not associated with deterioration in neurological status at 72 hours. Active treatment did not alter death or disability at 2 weeks. Borderline reductions in 90 day mortality with active treatment but small number of events. The CHHIPS pilot data emphasise the need for a full scale trial to see if these encouraging preliminary results can be reproduced.
179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5—16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome—death or dependency at 2 weeks—occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1·03, 95% CI 0·80—1·33; p=0·82). There was no evidence of early neurological deterioration with active treatment (RR 1·22, 0·33—4·54; p=0·76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17—25] mm Hg vs 11 [5—17] mm Hg; p=0·004). No increase in serious adverse events was reported with active treatment (RR 0·91, 0·69—1·12; p=0·50) but 3-month mortality was halved (9·7% vs 20·3%, hazard ratio [HR] 0·40, 95% CI 0·2—1·0; p=0·05).179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5—16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome—death or dependency at 2 weeks—occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1·03, 95% CI 0·80—1·33; p=0·82). There was no evidence of early neurological deterioration with active treatment (RR 1·22, 0·33—4·54; p=0·76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17—25] mm Hg vs 11 [5—17] mm Hg; p=0·004). No increase in serious adverse events was reported with active treatment (RR 0·91, 0·69—1·12; p=0·50) but 3-month mortality was halved (9·7% vs 20·3%, hazard ratio [HR] 0·40, 95% CI 0·2—1·0; p=0·05).
Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.
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Source of Information:
Presented at the ISC 2008.
Presented at the 30th International Stroke Conference [February 2005].
Stroke 2004 35: e359 - e368.
Abstract in Major Ongoing Stroke Trials at 2008 ISC meeting (February 2008).
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This information last updated on: 12/22/2008
Reviewed on: 12/22/2008.
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